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Matorras R, Sierra S, Pérez-Fernández S, Malaina I, Santos-Zorrozua B, Prieto B, Quintana F, Ferrando M, Rubio C, Gantxegi M. Influence of parental age on chromosomal abnormalities in PGT-A embryos: exponentially increasing in the mother and completely null in the father. J Assist Reprod Genet 2025:10.1007/s10815-025-03462-0. [PMID: 40205067 DOI: 10.1007/s10815-025-03462-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 03/14/2025] [Indexed: 04/11/2025] Open
Abstract
PURPOSE To study the influence of parental age on aneuploidy rates (AR) in PGT-A cycles and on the recurrence rate. METHODS A total of 16,029 PGT-A cycles were studied over a 9-year period. The median age was 40.0 [37.0; 41.0] in women and 40.0 [37.0; 43.0] in men. In 48.3%, the biopsy was performed on day 3 embryos (D3E) and in 51.7% on blastocysts (79.5% using NGS). RESULTS In women, the AR was almost constant at < 50% until the age of 35 but increased steadily to reach > 90% at 44. The AR pattern varied according to embryo stage and was considerably higher in D3E, with a steeper curve. A U-pattern was observed in D3E, whereas this was not seen in blastocysts. In the blastocysts analyzed using NGS, trisomy 21 increased sixfold (from < 1% at < 30 to nearly 5% in women aged 40), whereas trisomies 13 and 18 increased their frequency twofold. After 3 biopsied blastocysts studied using NGS, 100% of women aged ≤ 30 had at least 1 euploid embryo, vs 96% aged 31-35, almost 80% aged 36-40, 50% aged 41-45, and 33% aged 46-50. In terms of the man's age, the non-adjusted analysis revealed a correlation with AR. However, after correcting for the woman's age, no correlation was observed. The man's age was not associated with any of the aneuploidies potentially resulting in a newborn. CONCLUSIONS Carrying out PGT-A systematically in IVF cycles from the age of 38-39 is highly recommended. Advanced paternal age does not carry an increased risk of aneuploidy for the embryo and does not in itself constitute an indication for PGT-A.
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Affiliation(s)
- Roberto Matorras
- Instituto Valenciano de Infertilidad (IVI), IVIRMA, Bilbao, Spain
- Biobizkaia Health Research Institute, Baracaldo, Spain
- Human Reproduction Unit, Cruces University Hospital, Baracaldo, Spain
- Obstetrics and Gynecology Department, Basque Country University, Bilbao, Spain
| | - Silvia Sierra
- Human Reproduction Unit, Cruces University Hospital, Baracaldo, Spain
| | | | - Iker Malaina
- Department of Mathematics, Faculty of Science and Technology, University of the Basque Country, Vizcaya, Spain
| | | | - Begoña Prieto
- Instituto Valenciano de Infertilidad (IVI), IVIRMA, Bilbao, Spain
- Human Reproduction Unit, Cruces University Hospital, Baracaldo, Spain
- Obstetrics and Gynecology Department, Basque Country University, Bilbao, Spain
| | | | - Marcos Ferrando
- Instituto Valenciano de Infertilidad (IVI), IVIRMA, Bilbao, Spain
| | - Carmen Rubio
- EmbryoGenetics Department, Igenomix, Valencia, Spain
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Song J, Guo X, Zhang B, Zhang Q, Han Y, Cao D, Yao Y. Human Umbilical Cord Mesenchymal Stem Cells Derived Exosomes Improved The Aged Mouse IVM Oocytes Quality. Reprod Sci 2024; 31:2808-2819. [PMID: 38689080 DOI: 10.1007/s43032-024-01566-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 04/12/2024] [Indexed: 05/02/2024]
Abstract
During assisted reproductive technology (ART) treatment, the aged women, especially those over 35 years old, have fewer mature oocytes and poorer quality of the oocytes comparing with the young women. In vitro maturation (IVM) technology facilitates the usage of immature oocytes, which is clinically important for the aged women. However, the maturation rate is low for the oocytes from the aged women. Human umbilical cord mesenchymal stem cells derived exosomes (HUCMSCs-exosomes), as important mediators of intercellular communication, have been widely used to restore ovarian function and improve female fertility. In this study, we isolated HUCMSCs-exosomes and collected the immature germinal vesicle oocytes from the naturally aged mouse model. And we added these HUCMSCs-exosomes to the conventional IVM culture system. The effects of HUCMSCs-exosomes on IVM oocytes were observed and analyzed from multiple aspects including maturation rate, spindle morphology, mitochondria function, and development potential. We found the quality of oocytes was improved by HUCMSCs-exosomes. Based on the results, we propose that HUCMSCs-exosomes may provide a novel and cell free strategy in the improvement of the IVM in elderly infertile women in the future.
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Affiliation(s)
- Jiangnan Song
- Medical School of Chinese People's Liberation Army (PLA), Beijing, China
- Department of Gynecology and Obstetrics, Chinese PLA General Hospital, Beijing, China
- Shenzhen Key Laboratory of Fertility Regulation, Reproductive Medicine and Prenatal Diagnosis Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Xinmeng Guo
- College of Medicine, Nankai University, Tianjin, China
| | - Bolun Zhang
- Shenzhen Key Laboratory of Fertility Regulation, Reproductive Medicine and Prenatal Diagnosis Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
- College of Medicine, Nankai University, Tianjin, China
| | - Qian Zhang
- College of Medicine, Nankai University, Tianjin, China
| | | | - Dandan Cao
- Shenzhen Key Laboratory of Fertility Regulation, Reproductive Medicine and Prenatal Diagnosis Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
| | - Yuanqing Yao
- Department of Gynecology and Obstetrics, Chinese PLA General Hospital, Beijing, China.
- Shenzhen Key Laboratory of Fertility Regulation, Reproductive Medicine and Prenatal Diagnosis Center, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
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Teramoto N, Okada Y, Aburada N, Hayashi M, Ito J, Shirasuna K, Iwata H. Resveratrol intake by males increased the mitochondrial DNA copy number and telomere length of blastocysts derived from aged mice. J Reprod Dev 2024; 70:247-253. [PMID: 38945863 PMCID: PMC11310382 DOI: 10.1262/jrd.2024-043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Accepted: 06/03/2024] [Indexed: 07/02/2024] Open
Abstract
The present study examined whether male resveratrol intake affected mitochondrial DNA copy number (mt-cn) and telomere length (TL) in blastocysts fathered by young and aged male mice. C57BL/6N male mice supplied with water or water containing 0.1 mM resveratrol were used for embryo production at 14-23 and 48-58 weeks of age. Two-cell-stage embryos were collected from the oviducts of superovulated female mice (8-15 weeks old) and cultured for 3 days until the blastocyst stage. Mt-cn and TL levels were measured by real-time polymerase chain reaction. Resveratrol intake did not affect body weight or water consumption. Resveratrol intake increased the expression levels of SIRT1 in the liver, the antioxidative ability of serum, and extended TL in the heart, whereas there was no significant difference in mt-cn in the heart or TL in sperm. The rate of blastocyst development was significantly lower in aged male mice than in younger mice, and resveratrol intake increased the total number of blastocysts derived from both young and aged males. Resveratrol intake did not affect mt-cn or TL in blastomeres of blastocyst-stage embryos derived from young mice, but significantly increased both mt-cn and TL in blastomeres of blastocysts derived from aged fathers. In conclusion, resveratrol intake increased mt-cn and TL levels in blastocysts derived from aged male mice.
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Affiliation(s)
- Noko Teramoto
- Department of Animal Science, Tokyo University of Agriculture, Tokyo 156-8502, Japan
| | - Yuri Okada
- Department of Animal Science, Tokyo University of Agriculture, Tokyo 156-8502, Japan
| | - Nao Aburada
- Department of Animal Science, Tokyo University of Agriculture, Tokyo 156-8502, Japan
| | - Masamune Hayashi
- Department of Animal Science, Tokyo University of Agriculture, Tokyo 156-8502, Japan
| | - Jun Ito
- Department of Animal Science, Tokyo University of Agriculture, Tokyo 156-8502, Japan
| | - Komei Shirasuna
- Department of Animal Science, Tokyo University of Agriculture, Tokyo 156-8502, Japan
| | - Hisataka Iwata
- Department of Animal Science, Tokyo University of Agriculture, Tokyo 156-8502, Japan
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Alharbi B, Alqossayir F, Moalwi A, Alwashmi E, Alharbi AH, Aloraini A, Aljumah A, Alhomaidhi M, Almansour M. The Correlation of Paternal Age on Semen Parameters in Assisted Reproduction: A Retrospective Study in Qassim, Saudi Arabia. Cureus 2024; 16:e61632. [PMID: 38966445 PMCID: PMC11222903 DOI: 10.7759/cureus.61632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/04/2024] [Indexed: 07/06/2024] Open
Abstract
INTRODUCTION In the past, fertility concerns have predominantly revolved around the effect of a woman's age on the quality of her eggs and the success of her pregnancy. While men generally retain their ability to father children throughout their lives, there is evidence suggesting a decline in natural conception rates as paternal age increases. A growing body of research indicates a potential link between advanced paternal age (APA) and various adverse outcomes, including changes in sperm genetics, reduced conception rates, higher rates of miscarriage, lower live birth rates, and even long-term health consequences in offspring. However, it remains unclear whether there is an association between APA and the effectiveness of assisted reproductive technology (ART). This study aims to shed light on the relationship between APA and semen parameters. METHODOLOGY This is a retrospective, descriptive study analyzing data from electronic medical records of men undergoing ART at a fertility clinic in Saudia Arabia (2017-2022). Men aged 21-60 with at least one semen analysis and no missing data/hormonal treatment were included. Data on age and semen parameters (count, motility, and morphology) were extracted and analyzed using Jeffreys's Amazing Statistics Program (JASP; University of Amsterdam, Amsterdam, Netherlands) (descriptive statistics, Spearman's rank correlation). RESULTS Analysis of 1506 men undergoing ART revealed a mean age of 37 years (SD=6.94) and a mean sperm count of 55.0 million/mL (SD=46.05). The correlation between age and sperm count indicates a minimal association (r=0.075, p<0.01); moderate positive correlations were observed between sperm count and motility (r=0.406); count and morphology (r=0.543); and motility and morphology (r=0.458). CONCLUSION Age may not be a major factor in overall sperm parameters for this population, but a strong positive correlation was observed between sperm count, motility, and normal morphology. These findings suggest that these semen parameters are interconnected, with higher sperm counts potentially indicating better overall sperm quality.
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Affiliation(s)
- Badr Alharbi
- Department of Surgery, College of Medicine, Qassim University, Buraydah, SAU
| | - Fuhaid Alqossayir
- Department of Family and Community Medicine, College of Medicine, Qassim University, Buraydah, SAU
| | - Adel Moalwi
- Department of Surgery, College of Medicine, Najran University, Najran, SAU
| | - Emad Alwashmi
- Department of Surgery, College of Medicine, Qassim University, Buraydah, SAU
| | - Adel H Alharbi
- Department of Internal Medicine, College of Medicine, Qassim University, Buraydah, SAU
| | - Abdullah Aloraini
- Department of Surgery, College of Medicine, Qassim University, Buraydah, SAU
| | - Arwa Aljumah
- Department of Reproductive Medicine, Prince Faisal Bin Mishaal Fertility Center, Buraydah, SAU
| | - Manahil Alhomaidhi
- Department of Reproductive Medicine, Prince Faisal Bin Mishaal Fertility Center, Buraydah, SAU
| | - Mohammed Almansour
- Department of Urology, Imperial College London, London, GBR
- Department of Urology, King Fahd Specialist Hospital, Buraydah, SAU
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Kaltsas A, Zikopoulos A, Vrachnis D, Skentou C, Symeonidis EN, Dimitriadis F, Stavros S, Chrisofos M, Sofikitis N, Vrachnis N, Zachariou A. Advanced Paternal Age in Focus: Unraveling Its Influence on Assisted Reproductive Technology Outcomes. J Clin Med 2024; 13:2731. [PMID: 38792276 PMCID: PMC11122544 DOI: 10.3390/jcm13102731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 04/28/2024] [Accepted: 05/06/2024] [Indexed: 05/26/2024] Open
Abstract
As global demographics shift toward increasing paternal age, the realm of assisted reproductive technologies (ARTs), particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), faces new challenges and opportunities. This study provides a comprehensive exploration of the implications of advanced paternal age on ART outcomes. Background research highlights the social, cultural, and economic factors driving men toward later fatherhood, with a focus on the impact of delayed paternity on reproductive outcomes. Methods involve a thorough review of existing literature, centering on changes in testicular function, semen quality, and genetic and epigenetic shifts associated with advancing age. Study results point to intricate associations between the father's age and ART outcomes, with older age being linked to diminished semen quality, potential genetic risks, and varied impacts on embryo quality, implantation rates, and birth outcomes. The conclusions drawn from the current study suggest that while advanced paternal age presents certain risks and challenges, understanding and mitigating these through strategies such as sperm cryopreservation, lifestyle modifications, and preimplantation genetic testing can optimize ART outcomes. Future research directions are identified to further comprehend the epigenetic mechanisms and long-term effects of the older father on offspring health. This study underscores the need for a comprehensive approach in navigating the intricacies of delayed fatherhood within the context of ART, aiming for the best possible outcomes for couples and their children.
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Affiliation(s)
- Aris Kaltsas
- Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (A.K.); (M.C.)
- Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece;
| | - Athanasios Zikopoulos
- Department of Obstetrics and Gynecology, Royal Cornwall Hospital, Truro TR1 3LJ, UK;
| | - Dionysios Vrachnis
- Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Chara Skentou
- Department of Obstetrics and Gynaecology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece;
| | - Evangelos N. Symeonidis
- Department of Urology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (E.N.S.); (F.D.)
| | - Fotios Dimitriadis
- Department of Urology, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; (E.N.S.); (F.D.)
| | - Sofoklis Stavros
- Third Department of Obstetrics and Gynecology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.S.)
| | - Michael Chrisofos
- Third Department of Urology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (A.K.); (M.C.)
| | - Nikolaos Sofikitis
- Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece;
| | - Nikolaos Vrachnis
- Third Department of Obstetrics and Gynecology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece; (S.S.)
- Vascular Biology, Molecular and Clinical Sciences Research Institute, St George’s University of London, London SW17 0RE, UK
| | - Athanasios Zachariou
- Laboratory of Spermatology, Department of Urology, Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece;
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Liao M, Xu Q, Mao X, Zhang J, Wu L, Chen Q. Paternal age does not jeopardize the live birth rate and perinatal outcomes after in vitro fertilization: an analysis based on 56,113 frozen embryo transfer cycles. Am J Obstet Gynecol 2024; 230:354.e1-354.e13. [PMID: 37952870 DOI: 10.1016/j.ajog.2023.11.1224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 11/02/2023] [Accepted: 11/05/2023] [Indexed: 11/14/2023]
Abstract
BACKGROUND The global trend of delaying childbearing has led to an increasing number of couples seeking in vitro fertilization. The adverse effects of advanced maternal age on pregnancy and perinatal outcomes are well documented, regardless of the conception method. In addition, advanced paternal age may contribute to poor reproductive potential because of high levels of sperm DNA fragmentation. However, it remains challenging to guide older men regarding the effect of paternal age on pregnancy and birth outcomes in the field of assisted reproduction. OBJECTIVE This study aimed to investigate the association of paternal age with live birth and perinatal outcomes following in vitro fertilization-frozen embryo transfer. STUDY DESIGN A retrospective study was performed at a university-affiliated fertility center, involving women who were younger than 36 years and had undergone frozen embryo transfer from January 2011 to June 2021. Subjects were categorized into 6 groups based on paternal age: <25, 25 to 29, 30 to 34, 35 to 39, 40 to 44, and ≥45 years. A generalized estimating equation logistic regression model was used to account for the clustered nature of data and to adjust for confounders. Paternal age between 25 and 29 years served as the reference group in the logistic regression models. RESULTS A total of 56,113 cycles who met the inclusion criteria were included in the final analysis. On unadjusted analyses, the reproductive outcome parameters showed a considerable decline with increasing male age. The live birth rate decreased from 47.9% for men aged 25 to 29 years to 40.3% among men aged ≥40 years. Similarly, the clinical pregnancy rate decreased from 54.4% in the reference group to 47.8% in the ≥40 years age group. Conversely, the miscarriage rate increased as male age increased, from 10.2% among men aged 25 to 29 years to 13.5% among men aged ≥45 years. However, the differences in the reproductive outcomes mentioned above were no longer significant in the multivariable models. Compared with the younger controls, advanced paternal age was not associated with a lower chance of live birth (males aged 40-44 years: adjusted odds ratio, 0.94; 95% confidence interval, 0.85-1.04; males aged ≥45 years: adjusted odds ratio, 0.93; 95% confidence interval, 0.79-1.10). In addition, the rates of clinical pregnancy (males aged 40-44 years: adjusted odds ratio, 0.95; 95% confidence interval, 0.85-1.05; males aged ≥45 years: adjusted odds ratio, 0.94; 95% confidence interval, 0.79-1.12) and miscarriage (males aged 40-44 years: adjusted odds ratio, 1.05; 95% confidence interval, 0.85-1.31; males aged ≥45 years: adjusted odds ratio, 1.07; 95% confidence interval, 0.77-1.50) were comparable between the reference and advanced paternal age groups. Furthermore, men in the youngest age group (<25 years) did not have worse pregnancy outcomes than those in the reference group. Regarding perinatal outcomes, there was no difference among the study cohorts in terms of preterm birth, low birthweight, macrosomia, small for gestational age, and large for gestational age, both in the unadjusted and confounder-adjusted models. CONCLUSION This study did not demonstrate a significant association between paternal age and live birth and perinatal outcomes after in vitro fertilization-frozen embryo transfer when the female partners were younger than 36 years. With the global trend toward delaying childbirth, our findings provide useful information for counseling patients that increasing paternal age may not adversely affect pregnancy and perinatal outcomes in assisted reproduction.
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Affiliation(s)
- Maokun Liao
- Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qiuyu Xu
- Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaoyan Mao
- Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Zhang
- Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Ling Wu
- Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Qiuju Chen
- Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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Farabet C, Pirtea P, Benammar A, De Ziegler D, Marchiori C, Vallée A, Ayoubi JM. The impact of paternal age on cumulative assisted reproductive technology outcomes. Front Med (Lausanne) 2024; 10:1294242. [PMID: 38298503 PMCID: PMC10828963 DOI: 10.3389/fmed.2023.1294242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 11/29/2023] [Indexed: 02/02/2024] Open
Abstract
Objective To investigate the impact of paternal age on cumulative live birth rate in ART. Design Retrospective single-center cohort study. Patients All female patients aged 18-43 years and male patients aged 18-60 years, who performed their first ART cycle between January 2018 and December 2020, were included. Main outcome measures The primary outcome, cumulative live birth rate (cLBR), was estimated following fresh or frozen embryo transfers issued from an ART cycle. Secondary outcomes included the cumulative pregnancy rate (cPR) and miscarriage rate. Subgroup analyzes were performed as follows: men <45 and ≥ 45; female <35, 35-38, and > 38 years. Results A total of 2,358 couples were included in this study. The sperm quantity of male patients within both age groups was divided in two groups: normal and abnormal, which were found to be in significantly equal proportions. There were significantly fewer current smokers in the male group ≥45. The cPR was 0.5301 in the group <45 and 0.3111 in the group ≥45, with a p-value <0.001. Analysis according to the female age revealed that, in the female group >38, the cLBR rate was 0.26 for men <45 and 0.19 for men ≥45, with a p-value of 0.061. Additionally, the cPR was 0.34 in the male group <45 and 0.21 in the group ≥45, with a p-value <0.001. In the female group between 35 and 38 years of age, the cLBR was 0.44 in the male group <45 and 0.3 in the male group ≥45, with a p-value of 0.031. The cPR was 0.49 in the male group <45 and 0.34 in the group ≥45, p = 0.036. Within the female group <35, we observed non-significant results. The miscarriage rate results were not significantly different for women ≤38. Conclusion According to the results from our study, male age ≥ 45 has a significant impact on cumulative ART outcomes.
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Affiliation(s)
| | - Paul Pirtea
- Department of Obstetrics, Gynecology and Assisted Reproduction, Hospital FOCH, Suresnes, France
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Shacfe G, Turko R, Syed HH, Masoud I, Tahmaz Y, Samhan LM, Alkattan K, Shafqat A, Yaqinuddin A. A DNA Methylation Perspective on Infertility. Genes (Basel) 2023; 14:2132. [PMID: 38136954 PMCID: PMC10743303 DOI: 10.3390/genes14122132] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 11/24/2023] [Accepted: 11/25/2023] [Indexed: 12/24/2023] Open
Abstract
Infertility affects a significant number of couples worldwide and its incidence is increasing. While assisted reproductive technologies (ART) have revolutionized the treatment landscape of infertility, a significant number of couples present with an idiopathic cause for their infertility, hindering effective management. Profiling the genome and transcriptome of infertile men and women has revealed abnormal gene expression. Epigenetic modifications, which comprise dynamic processes that can transduce environmental signals into gene expression changes, may explain these findings. Indeed, aberrant DNA methylation has been widely characterized as a cause of abnormal sperm and oocyte gene expression with potentially deleterious consequences on fertilization and pregnancy outcomes. This review aims to provide a concise overview of male and female infertility through the lens of DNA methylation alterations.
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Affiliation(s)
| | | | | | | | | | | | | | - Areez Shafqat
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia; (G.S.); (R.T.); (H.H.S.); (I.M.); (Y.T.); (L.M.S.); (K.A.); (A.Y.)
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9
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Aitken RJ. Male reproductive ageing: a radical road to ruin. Hum Reprod 2023; 38:1861-1871. [PMID: 37568254 PMCID: PMC10546083 DOI: 10.1093/humrep/dead157] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 07/21/2023] [Indexed: 08/13/2023] Open
Abstract
In modern post-transition societies, we are reproducing later and living longer. While the impact of age on female reproductive function has been well studied, much less is known about the intersection of age and male reproduction. Our current understanding is that advancing age brings forth a progressive decline in male fertility accompanied by a reduction in circulating testosterone levels and the appearance of age-dependent reproductive pathologies including benign prostatic hypertrophy and erectile dysfunction. Paternal ageing is also associated with a profound increase in sperm DNA damage, the appearance of multiple epigenetic changes in the germ line and an elevated mutational load in the offspring. The net result of such changes is an increase in the disease burden carried by the progeny of ageing males, including dominant genetic diseases such as Apert syndrome and achondroplasia, as well as neuropsychiatric conditions including autism and spontaneous schizophrenia. The genetic basis of these age-related effects appears to involve two fundamental mechanisms. The first is a positive selection mechanism whereby stem cells containing mutations in a mitogen-activated protein kinase pathway gain a selective advantage over their non-mutant counterparts and exhibit significant clonal expansion with the passage of time. The second is dependent on an age-dependent increase in oxidative stress which impairs the steroidogenic capacity of the Leydig cells, disrupts the ability of Sertoli cells to support the normal differentiation of germ cells, and disrupts the functional and genetic integrity of spermatozoa. Given the central importance of oxidative stress in defining the impact of chronological age on male reproduction, there may be a role for antioxidants in the clinical management of this process. While animal studies are supportive of this strategy, carefully designed clinical trials are now needed if we are to realize the therapeutic potential of this approach in a clinical context.
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Affiliation(s)
- R John Aitken
- Priority Research Centre for Reproductive Science, Discipline of Biological Sciences, School of Environmental and Life Sciences, College of Engineering Science and Environment, University of Newcastle, Callaghan, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
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Wang P, Zhao C, Xu W, Jin X, Zhang S, Zhu H. The association between the number of oocytes retrieved and cumulative live birth rate in different female age strata. Sci Rep 2023; 13:14516. [PMID: 37667038 PMCID: PMC10477298 DOI: 10.1038/s41598-023-41842-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 08/31/2023] [Indexed: 09/06/2023] Open
Abstract
To evaluate the association between the number of oocytes retrieved and cumulative live birth rate (CLBR) in different female age strata. 17,931 women undergoing their first IVF/ICSI-ET cycle in the Sir Run Run Shaw Hospital of Zhejiang University were grouped by age (A: ≤ 35 years; B: ≥ 36 years) as well as the number of oocytes retrieved (a: ≤ 5; b:6-9; c:10-14; d: ≥ 15). Multivariate regression analysis was performed to assess the OR of CLBR for the variable 'age' and 'number of oocytes retrieved'. The group ≥ 36 years exhibited lower cumulative pregnancy rates (CPRs) and cumulative live birth rates (CLBRs), which are proportional to the number of oocytes retrieved but opposite to increasing age. Multivariate logistic regression analysis revealed that the age and number of oocytes retrieved remain significant independent predictive factors (P < 0.001). Age and number of oocytes retrieved are two independent factors affecting the CLBR. The discrepancy of the minimum number of oocytes retrieved for patients with different ages to achieve ideal CLBR is instructive for clinical practice. The practice of controlling the stimulation dose is feasible for patients ≤ 35 years who can achieve over 60% CLBR once the number of oocytes obtained is more than 6. However, additional stimulation cycles and accumulation of embryos are necessary for elderly group especially those ≥ 38 years old who need more than 14 oocytes to obtain higher live birth rate.
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Affiliation(s)
- Peixin Wang
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, 310016, China
| | - Chenqiong Zhao
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, 310016, China
| | - Wen Xu
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, 310016, China
| | - Xiaoying Jin
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, 310016, China
| | - Songying Zhang
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, 310016, China
| | - Haiyan Zhu
- Assisted Reproduction Unit, Department of Obstetrics and Gynecology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
- Key Laboratory of Reproductive Dysfunction Management of Zhejiang Province, Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, 310016, China.
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11
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Gao J, Liu Z, Zhong Y, Li N, Tang T. Factors influencing clinical pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection in older women. Afr Health Sci 2023; 23:632-639. [PMID: 38223645 PMCID: PMC10782308 DOI: 10.4314/ahs.v23i2.73] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2024] Open
Abstract
Objective To analyse the factors influencing clinical pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) in older women, and to establish a risk prediction model. Methods A total of 425 patients receiving IVF/ICSI from March 2018 to March 2020 were divided into pregnancy group (n=194) and non-pregnancy group (n=231). The factors affecting the outcomes of IVF/ICSI were explored by univariate and multivariate logistic regression analyses. A nomogram prediction model was constructed. Results The two groups had significantly different age, body mass index, dysmenorrhea, parity, times of full-term births, history of cesarean section, basal follicle stimulating hormone, basal antral follicle count (AFC), number of high-quality embryos, and basal estradiol, luteinizing hormone and endometrial thickness on the day of human chorionic gonadotropin (HCG) administration (P<0.05). Age ≥40 years old, dysmenorrhea, history of cesarean section, basal AFC<9, number of high-quality embryos <4, and endometrial thickness on the day of HCG administration <11 mm led to IVF/ICSI failure. The established model exhibited high calibration and discrimination degrees in predicting the outcome of IVF/ICSI. Conclusion The risk prediction model for the pregnancy outcome of IVF/ICSI in older women helps evaluate the fertility probability and risk, providing references for formulating reasonable assisted reproduction plans.
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Affiliation(s)
- Jinyu Gao
- Reproductive Medicine Center, Hunan Provincial Maternal and Child Health Care Hospital, Hu'nan Province, China
| | - Zhaohua Liu
- Reproductive Medicine Center, Hunan Provincial Maternal and Child Health Care Hospital, Hu'nan Province, China
| | - Yao Zhong
- Reproductive Medicine Center, Hunan Provincial Maternal and Child Health Care Hospital, Hu'nan Province, China
| | - Nannan Li
- Reproductive Medicine Center, Hunan Provincial Maternal and Child Health Care Hospital, Hu'nan Province, China
| | - Tingting Tang
- Reproductive Medicine Center, Hunan Provincial Maternal and Child Health Care Hospital, Hu'nan Province, China
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12
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Si M, Jiang H, Zhao Y, Qi X, Li R, Long X, Qiao J. Nomogram for Predicting Live Birth after the First Fresh Embryo Transfer in Patients with PCOS Undergoing IVF/ICSI Treatment with the GnRH-Ant Protocol. Diagnostics (Basel) 2023; 13:diagnostics13111927. [PMID: 37296779 DOI: 10.3390/diagnostics13111927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2023] [Revised: 05/28/2023] [Accepted: 05/29/2023] [Indexed: 06/12/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. A better understanding of factors associated with pregnancy outcomes and successful prediction of live birth after IVF/ICSI are important to guide clinical practice. This was a retrospective cohort study investigating live birth after the first fresh embryo transfer using the GnRH-ant protocol in patients with PCOS between 2017 and 2021 at the Reproductive Center of Peking University Third Hospital. A total of 1018 patients with PCOS were qualified for inclusion in this study. BMI, AMH level, initial FSH dosage, serum LH and progesterone levels on the hCG trigger day, and endometrial thickness were all independent predictors of live birth. However, age and infertility duration were not significant predictors. We developed a prediction model based on these variables. The predictive ability of the model was demonstrated well, with areas under the curve of 0.711 (95% CI, 0.672-0.751) and 0.713 (95% CI, 0.650-0.776) in the training cohort and validation cohort, respectively. Additionally, the calibration plot showed good agreement between the prediction and the observation (p = 0.270). The novel nomogram could be helpful for clinicians and patients in clinical decision-making and outcome evaluation.
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Affiliation(s)
- Manfei Si
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
| | - Huahua Jiang
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
| | - Yue Zhao
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
| | - Xinyu Qi
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
| | - Rong Li
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
| | - Xiaoyu Long
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
| | - Jie Qiao
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
- Key Laboratory of Assisted Reproduction, Peking University, Ministry of Education, Beijing 100191, China
- Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China
- Beijing Advanced Innovation Center for Genomics, Beijing 100191, China
- Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100191, China
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13
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Lewin J, Lukaszewski T, Sangster P, Williamson E, McEleny K, Al Wattar BH, Yasmin E. Reproductive outcomes after surgical sperm retrieval in couples with male factor subfertility: a 10-year retrospective national cohort. Fertil Steril 2023; 119:589-595. [PMID: 36592648 DOI: 10.1016/j.fertnstert.2022.12.041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2022] [Revised: 12/24/2022] [Accepted: 12/28/2022] [Indexed: 01/01/2023]
Abstract
OBJECTIVE To determine any significant differences in the reproductive outcome from intracytoplasmic sperm injection (ICSI) with surgical sperm retrieval (SSR) between cycles using fresh and cryopreserved sperm and between cycles using epididymal and testicular sperm. DESIGN A retrospective national cohort study using data from the UK Human Fertilisation and Embryology Authority, including all ICSI cycles performed in the United Kingdom over a 10-year period. SETTING Hospital. PATIENT(S) All nondonor ICSI cycles from 2008 to 2017 categorized by sperm source and cryopreservation status. INTERVENTION(S) Intracytoplasmic sperm injection with SSR using fresh or cryopreserved sperm and using ejaculated, testicular, and epididymal sperm. MAIN OUTCOME MEASURE(S) Live birth rate, pregnancy rate, and implantation rate. RESULT(S) We analyzed data from 214,649 ICSI cycles, including 199,818 cycles of ejaculated sperm, 5,646 cycles of epididymal sperm, and 9,185 cycles of testicular sperm. Live births rates per ICSI cycle were 28.5%, 30.6%, and 28.7% for ejaculated, epididymal, and testicular sperm cycles, respectively. Epididymal sperm cycles had a higher live birth rate than that of testicular sperm cycles (odds ratio [OR], 1.067; 95% confidence interval [CI], 1.014-1.123). This was despite a higher mean male age (42.5 vs. 40.6 years; 95% CI of difference, 1.81-1.85 years) and female age (34.3 vs. 34.0 years; 95% CI of difference, 0.32-0.34 years) in epididymal cycles than in testicular cycles. Implantation (61.2% vs. 58.0%; OR, 1.086; 95% CI, 1.041-1.133) and clinical pregnancy rates (34.3% vs. 31.3%; OR, 1.085; 95% CI, 1.039-1.132) were also higher in epididymal cycles than in testicular cycles. There were no statistically significant differences in outcomes between cycles using fresh sperm and those using cryopreserved sperm for SSR-ICSI. CONCLUSION(S) Our study indicates that reproductive outcomes of SSR-ICSI are at least comparable with those of ICSI using ejaculated sperm and does not support the preferential use of fresh sperm over cryopreserved sperm in SSR-ICSI. Births per SSR-ICSI cycle were higher for cycles using epididymal sperm than for cycles using testicular sperm; however, the differences were small, which may provide reassurance to patients undergoing these procedures. The results must be interpreted with caution because multivariable analysis was not possible because of aggregation of data.
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Affiliation(s)
- Jonathan Lewin
- Reproductive Medicine Unit, University College London Hospitals, London, United Kingdom; UCL Institute for Women's Health, University College London, London, United Kingdom
| | - Tomasz Lukaszewski
- Reproductive Medicine Unit, University College London Hospitals, London, United Kingdom
| | - Phillippa Sangster
- Reproductive Medicine Unit, University College London Hospitals, London, United Kingdom; Department of Urology, University College London Hospitals, London, United Kingdom
| | - Elizabeth Williamson
- Reproductive Medicine Unit, University College London Hospitals, London, United Kingdom
| | - Kevin McEleny
- Newcastle Fertility Centre, Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, United Kingdom
| | - Bassel H Al Wattar
- Reproductive Medicine Unit, University College London Hospitals, London, United Kingdom; UCL Institute for Women's Health, University College London, London, United Kingdom
| | - Ephia Yasmin
- Reproductive Medicine Unit, University College London Hospitals, London, United Kingdom; UCL Institute for Women's Health, University College London, London, United Kingdom.
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14
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Abstract
Compared to women, increasing male age is not accompanied by such marked changes in reproductive function but changes certainly do happen. These include alterations to the hypothalamo-pituitary-testicular axis, with resultant implications for testosterone production and bioavailability as well as spermatogenesis. There is a decline in sexual function as men age, with a dramatic increase in the prevalence of erectile dysfunction after the age of 40, which is a marker for both clinically evident as well as covert coronary artery disease. Despite a quantitative decline in spermatogenesis and reduced fecundability, the male potential for fertility persists throughout adult life, however there are also increasingly recognised alterations in sperm quality and function with significant implications for offspring health. These changes are relevant to both natural and medically assisted conception.
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Affiliation(s)
- Sarah Martins da Silva
- Reproductive Medicine Research Group, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, DD1 9SY, Dundee, UK
| | - Richard A Anderson
- MRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, EH16 4TJ, Edinburgh, UK.
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15
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Yang Q, Hu J, Wang M, Guo N, Yang L, Xi Q, Zhu L, Jin L. Rapamycin improves the quality and developmental competence of in vitro matured oocytes in aged mice and humans. Aging (Albany NY) 2022; 14:9200-9209. [PMID: 36441531 PMCID: PMC9740364 DOI: 10.18632/aging.204401] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 11/17/2022] [Indexed: 11/29/2022]
Abstract
Women over age 35 suffer from the inadequate number and poor quality of oocytes during assisted reproductive treatment, and making full use of the oocytes by in vitro maturation (IVM) is crucial. Rapamycin could improve the developmental competences of the post-maturation oocytes during in vitro aging, yet its effects on the IVM process of oocytes from an aged population were not clear. In this study, the immature oocytes from aged mice or older women underwent IVM with or without 10 nM rapamycin, followed by parthenogenetic activation or insemination and embryo culture. The developmental competence and quality of IVM oocytes in both groups were compared. The results showed that in aged mice, the maturation rate, activation rate, and cleavage rate of IVM oocytes were significantly elevated in the rapamycin group. Additionally, oocytes cultured with rapamycin presented decreased ROS levels, reduced chromosome aberration, and attenuated levels of γ-H2AX. During IVM of oocytes from older women, the GVBD rate, 24 h maturation rate, and 48 h maturation rate were increased in the rapamycin group, compared with those in the control group, although without significant differences. After intracytoplasmic sperm injection (ICSI) and further culture of human oocytes, the high-quality embryo rate in the rapamycin group was significantly elevated. Overall, rapamycin improved IVM outcomes of oocytes from aged mice and older women. The specific mechanism of the positive effects of rapamycin on IVM outcomes might be reducing ROS levels, mitigating DNA damage, and promoting developmental potential.
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Affiliation(s)
- Qiyu Yang
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Juan Hu
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Meng Wang
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Na Guo
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Liu Yang
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qingsong Xi
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lixia Zhu
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Jin
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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16
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Chen H, Sun ZL, Chen MX, Yang Y, Teng XM, Wang Y, Wu YY. Predicting the probability of a live birth after a freeze-all based in vitro fertilization-embryo transfer (IVF-ET) treatment strategy. Transl Pediatr 2022; 11:797-812. [PMID: 35800265 PMCID: PMC9253936 DOI: 10.21037/tp-21-589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 04/02/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND The predictors for live birth rate (LBR) following one episode of in vitro fertilization (IVF) cycle for patients using a "freeze-all" strategy are not entirely clear. METHODS A retrospective cohort study utilizing a prediction model was developed to assess the relationship to the LBR. Women undergoing IVF with a freeze-all strategy were screened. Univariate models were first fitted for female age at oocytes retrieval/frozen-thawed embryo transfer (FET), body mass index (BMI), duration and etiology of infertility, previous IVF failures, total dose and duration of gonadotrophin, ovarian sensitivity index (OSI), number of oocytes collected, method of fertilization, number of embryos created, number and stage of embryos frozen, type and number of FET cycles, endometrial thickness (EMT)/pattern, hormone level on transplantation day, storage duration, number of embryos thawed and damaged thawed embryos, number and stage of embryos transferred and number of different quality embryos transferred. Variables with P<0.05 in the univariate model were selected for further analysis of the final multivariate discrete-time logistic regression model. RESULTS A total of 7,602 women undergoing one ovarian stimulation resulted in 9,964 FETs, of whom 3,066 (40.33%) had a live-birth after their first FET and 3,929 (51.68%) after total FETs. The EMT and woman's age at oocyte retrieval were the most important predictors. In the first FET, the LBR of women with an EMT ≤8 mm [27.40%; 95% confidence interval (CI): (21.60-33.81%)] was significantly lower than that of women with EMT between 9 and 11 mm [36.51%; 95% CI: (34.25-38.81%)] and thicker than 12 mm [44.23%; 95% CI: (42.22-46.25%)] (P<0.05). The optimistic and conservative cumulative LBRs of women younger than 31 years [87.5%; 95% CI: (86.32-88.61%) and 63.04%; 95% CI: (61.36-64.69%)] were significantly decreased in women aged 31-35, 36-40 and >40 (P<0.001). CONCLUSIONS Our study provides an effective prediction model for a woman's chance of having a baby after a "freeze-all" policy. The use of EMT and female age as tools to identify LBR are shown to be justified, and repeated FETs cannot reverse the age-dependent decline in fertility.
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Affiliation(s)
- Hong Chen
- Department of Assisted Reproduction, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
| | - Zi-Li Sun
- Department of Assisted Reproduction, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
| | - Miao-Xin Chen
- Department of Assisted Reproduction, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yang Yang
- Department of Assisted Reproduction, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiao-Ming Teng
- Department of Assisted Reproduction, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
| | - Yun Wang
- Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuan-Yuan Wu
- Department of Assisted Reproduction, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
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17
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Does advanced paternal age affect outcomes following artificial reproductive technologies? A systematic review and meta-analysis. Reprod Biomed Online 2022; 45:283-331. [DOI: 10.1016/j.rbmo.2022.03.031] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2021] [Revised: 03/18/2022] [Accepted: 03/31/2022] [Indexed: 11/20/2022]
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18
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Torra-Massana M, Quintana-Vehí A, Barragán M, Bellido R, Rodríguez A, Vassena R. How long can the sperm wait? Effect of incubation time on ICSI outcomes. Mol Reprod Dev 2022; 89:133-145. [PMID: 35195315 DOI: 10.1002/mrd.23561] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 12/03/2021] [Accepted: 01/10/2022] [Indexed: 11/11/2022]
Abstract
In sperm processing for IVF/ICSI incubation times differ considerably both between and within assisted reproduction facilities. There is no established consensus on the optimal sperm incubation timings to maximize pregnancy rates, and the few studies addressing this association rely on manual and operator-dependent methods for time recording. The present retrospective cohort study includes 1169 ICSI cycles using fresh semen processed by swim-up. An operator-independent, radiofrequency-based system was used to record sperm incubation times: from sample collection to swim-up (T1, 0.35 ± 0.26); from swim-up to ICSI (T2, 3.30 ± 2.2); and total time from sample collection to ICSI (T, 3.66 ± 2.26). In oocyte donation cycles, we observed a significant negative effect of T1 on fertilization rate (FR; generalized linear modelling regression, coeff. -0.20, p = 0.001); however, after analysing all times by deciles and by adjusted logistic regression, none of the time intervals had a significant effect on pregnancy (biochemical, clinical, and ongoing) and live birth (LB) rates (p > 0.05 for all outcomes). In cycles using the patient's oocytes, we observed a negative effect of T2 (ordinal regression, coeff. -0.25, p = 0.011) and T (-0.33, p = 0.005) on the mean morphological score of the embryo cohort. In these cycles, a trend associating longer values of T with higher LB rates was identified (OR = 1.47, p = 0.050), although this difference is likely not clinically significant. In conclusion, while longer sperm incubation in vitro may impact slightly both FRs and embryo morphology after ICSI, no adverse effects were detected on the reproductive outcomes.
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19
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Zhu YC, Sun YX, Shen XY, Jiang Y, Liu JY. Effect of intrauterine perfusion of granular leukocyte-colony stimulating factor on the outcome of frozen embryo transfer. World J Clin Cases 2021; 9:9038-9049. [PMID: 34786386 PMCID: PMC8567495 DOI: 10.12998/wjcc.v9.i30.9038] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 08/04/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Treatment of thin endometrium with granular leukocyte-colony stimulating factor (G-CSF) remains controversial.
AIM To investigate the effect of G-CSF on the outcome of frozen embryo transfer in patients with thin endometrium.
METHODS A retrospective propensity score matching (PSM) study was performed to assess patients administered frozen embryo transfer at the Reproductive Medicine Center of the Affiliated Drum Tower Hospital of Nanjing University Medical School, in 2012-2018. The patients were divided into G-CSF intrauterine perfusion (G-CSF) and non-G-CSF groups, and clinical pregnancy, implantation, ectopic pregnancy, and early abortion rates between the two groups were compared.
RESULTS Before PSM, 372 cycles were enrolled, including 242 and 130 cycles in the G-CSF and non-G-CSF groups, respectively. Age (34.23 ± 5.76 vs 32.99 ± 5.59 years; P = 0.047) and the blastula/cleavage stage embryo ratio (0.68 vs 0.37; P = 0.011) were significantly elevated in the G-CSF group compared with the non-G-CSF group; however, clinical pregnancy (46.28% vs 51.54%; P = 0.371) and embryo implantation (35.21% vs 35.65%; P = 0.910) rates were similar in both groups. After PSM by age and blastula/cleavage stage embryo ratio, 244 cycles were included (122 cases each in the G-CSF and non-G-CSF groups). The clinical pregnancy (50.82 % vs 48.36%; P = 0.701) and embryo implantation (37.38% vs 34.11%; P = 0.480) remained similar in both groups.
CONCLUSION Intrauterine infusion of G-CSF does not improve the clinical outcome of frozen embryo transfer in patients with thin endometrium.
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Affiliation(s)
- Ying-Chun Zhu
- Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Yan-Xin Sun
- Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Xiao-Yue Shen
- Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Yue Jiang
- Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Jing-Yu Liu
- Reproductive Medicine Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
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20
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Morris G, Mavrelos D, Odia R, Viñals Gonzalez X, Cawood S, Yasmin E, Saab W, Serhal P, Seshadri S. Paternal age over 50 years decreases assisted reproductive technology (ART) success: A single UK center retrospective analysis. Acta Obstet Gynecol Scand 2021; 100:1858-1867. [PMID: 34405396 DOI: 10.1111/aogs.14221] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 06/23/2021] [Accepted: 06/24/2021] [Indexed: 12/15/2022]
Abstract
INTRODUCTION To study whether paternal age exerts an effect, independent of maternal age, on the outcomes of fresh in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles. Semen quality deteriorates with increasing paternal age; however, there is conflicting evidence for any impact paternal age may have on the outcome of IVF/ICSI. Several retrospective and prospective cohort studies have shown that paternal age increases the miscarriage rate and reduces the live birth rate. Some studies have shown no effect of paternal age on live birth rate or miscarriage rate. Studies involving donor oocytes have tended to show no independent effect of paternal age on assisted reproductive technology (ART) outcomes. The age at which paternal age may exert a significant deleterious effect on outcome is not known and there is no limit to paternal age in IVF/ICSI treatment. MATERIAL AND METHODS A single-center retrospective cohort study was carried out at the Centre for Reproductive and Genetic Health, London, UK. Included in the analysis were all couples with primary or secondary infertility undergoing IVF/ICSI cycles in which the male partner produced a fresh semen sample and the cycle proceeded to fresh embryo transfer. All cycles of IVF/ICSI that used donor oocytes-donor sperm, frozen sperm, cycles leading to embryo storage and cycles including preimplantation genetic testing (PGT-A/PGT-M)-were excluded from analysis. The primary outcome was live birth rate and secondary outcomes were clinical pregnancy rate and miscarriage rate. Multivariate logistic regression analysis with live birth as a dependent variable and maternal and paternal age class as independent variables was performed. RESULTS During the study period there were 4833 cycles, involving 4271 men, eligible for analysis; 1974/4833 (40.8%, 95% confiene intervals [CI] 39.5-42.2%) cycles resulted in a live birth. A significantly lower proportion of men over 51 years met World Health Organization semen analysis criteria (56/133, [42.1%, 95% CI 34.1-50.6]) compared with men under 51 years of age (2530/4138 [61.1%, 95% CI 60.0-62.6]) (p = 0.001). Both maternal and paternal age were retained in the multivariate model and for all maternal age subgroups the probability of live birth decreased with paternal age over 50 years (odds ratio [OR] 0.674, 95% CI 0.482-0.943) (p = 0.021). Paternal age over 50 years was not an independent predictor of miscarriage (OR 0.678, 95% CI 0.369-1.250) (p = 0.214). CONCLUSIONS Paternal age over 50 significantly affects the chance of achieving a live birth following ART. Paternal age does not independently affect the risk of miscarriage following ART. There should be a public health message for men not to delay fatherhood.
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Affiliation(s)
- Guy Morris
- Centre for Reproductive and Genetic Health, London, UK.,Reproductive Medicine Unit, University College London Hospitals NHS Foundation Trust, London, UK
| | - Dimitrios Mavrelos
- Centre for Reproductive and Genetic Health, London, UK.,Reproductive Medicine Unit, University College London Hospitals NHS Foundation Trust, London, UK
| | - Rabi Odia
- Centre for Reproductive and Genetic Health, London, UK
| | | | | | - Ephia Yasmin
- Centre for Reproductive and Genetic Health, London, UK.,Reproductive Medicine Unit, University College London Hospitals NHS Foundation Trust, London, UK
| | - Wael Saab
- Centre for Reproductive and Genetic Health, London, UK
| | - Paul Serhal
- Centre for Reproductive and Genetic Health, London, UK
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21
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Marsidi AM, Kipling LM, Kawwass JF, Mehta A. Influence of paternal age on assisted reproductive technology cycles and perinatal outcomes. Fertil Steril 2021; 116:380-387. [PMID: 33910758 DOI: 10.1016/j.fertnstert.2021.03.033] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 03/20/2021] [Accepted: 03/22/2021] [Indexed: 12/25/2022]
Abstract
OBJECTIVE To characterize paternal age among assisted reproductive technology (ART) cycles performed in the United States and to evaluate the influence of paternal age on ART cycles and perinatal outcomes. DESIGN Retrospective cohort. SETTING Not applicable. PATIENT(S) All reported fresh, nondonor, noncancelled in vitro fertilization (IVF) cycles performed in 2017. INTERVENTION(S) Not applicable. MAIN OUTCOME MEASURE(S) The primary outcomes were intrauterine pregnancy, live birth (≥20 weeks), and miscarriage (<20 weeks) per cycle start and per embryo transfer. The secondary outcomes were full-term live birth (≥37 weeks) among singleton and twin gestations. Modified Poisson regression was performed to estimate associations between paternal age and cycle and perinatal outcomes, overall and stratified by maternal age. RESULT(S) Among 77,209 fresh nondonor, noncancelled IVF cycles, the average paternal age was 37.8 ± 6.3 years and the average maternal age was 35.5 ± 4.6 years. Compared with paternal age ≤45 years, paternal age ≥46 years was associated with a lower likelihood of pregnancy per cycle (adjusted risk ratio [aRR] 0.81; 95% confidence interval [CI] 0.76-0.87) and per transfer (aRR 0.85; 95% CI 0.81-0.90), as well as a lower likelihood of live birth per cycle (aRR 0.76; 95% CI 0.72-0.84) and per transfer (aRR 0.82; 95% CI 0.77-0.88) after controlling for maternal age and other confounders. When restricted to women aged <35 years, there were no significant differences in the rates of live birth or miscarriage among couples in which the men were aged ≤45 years compared with those aged ≥46 years. CONCLUSION(S) Compared with paternal age ≤45 years, paternal age ≥46 years is associated with a lower likelihood of pregnancy and live birth among couples undergoing IVF. The negative effect of paternal age is most notable among women aged ≥35 years, likely because maternal age is a stronger predictor of ART outcome.
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Affiliation(s)
- Audrey M Marsidi
- Division of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Emory Reproductive Center, Atlanta, Georgia.
| | - Lauren M Kipling
- Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, Georgia
| | - Jennifer F Kawwass
- Division of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Emory Reproductive Center, Atlanta, Georgia
| | - Akanksha Mehta
- Department of Urology, Emory University School of Medicine, Atlanta, Georgia
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22
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Improving Sperm Oxidative Stress and Embryo Quality in Advanced Paternal Age Using Idebenone In Vitro-A Proof-of-Concept Study. Antioxidants (Basel) 2021; 10:antiox10071079. [PMID: 34356315 PMCID: PMC8301200 DOI: 10.3390/antiox10071079] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 06/25/2021] [Accepted: 07/02/2021] [Indexed: 12/29/2022] Open
Abstract
Advanced paternal age is associated with increased sperm reactive oxygen species (ROS) and decreased fertilization and pregnancy rates. Sperm washing during infertility treatment provides an opportunity to reduce high sperm ROS concentrations associated with advanced paternal age through the addition of idebenone. Sperm from men aged >40 years and older CBAF1 mice (12–18 months), were treated with 5 µM and 50 µM of idebenone and intracellular and superoxide ROS concentrations assessed. Following in vitro fertilization (IVF), embryo development, blastocyst differentiation, DNA damage and cryosurvival, pregnancy and implantation rates and fetal and placental weights were assessed. Five µM of idebenone given to aged human and mouse sperm reduced superoxide concentrations ~20% (p < 0.05), while both 5 and 50 µM reduced sperm intracellular ROS concentrations in mice ~30% (p < 0.05). Following IVF, 5 µM of idebenone to aged sperm increased fertilization rates (65% vs. 60%, p < 0.05), blastocyst total, trophectoderm and inner cell mass cell numbers (73 vs. 66, 53 vs. 47 and 27 vs. 24, respectively, p < 0.01). Treatment with idebenone also increased blastocyst cryosurvival rates (96% vs. 78%, p < 0.01) and implantation rates following embryo transfer (35% vs. 18%, p < 0.01). Placental weights were smaller (107 mg vs. 138 mg, p < 0.05), resulting in a larger fetal to placental weight ratio (8.3 vs. 6.3, p = 0.07) after sperm idebenone treatment. Increased sperm ROS concentrations associated with advanced paternal age are reduced with the addition of idebenone in vitro, and are associated with improved fertilization rates, embryo quality and implantation rates after IVF.
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23
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Tarozzi N, Nadalini M, Coticchio G, Zacà C, Lagalla C, Borini A. The paternal toolbox for embryo development and health. Mol Hum Reprod 2021; 27:6311671. [PMID: 34191013 DOI: 10.1093/molehr/gaab042] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 05/30/2021] [Indexed: 11/12/2022] Open
Abstract
The sperm is essential for reconstitution of embryonic diploidy and highly specialized developmental functions. Immediately after gamete fusion, the sperm-borne PLC-zeta triggers activation, generating intracellular free Ca2+ oscillations. Mutations in the PLC-zeta encoding gene are associated with the absence of this factor in mature sperm and inability to achieve fertilization. Sperm play also a role in the greater game of the choreography of fertilization. In the human, the sperm centrioles are introduced into the oocyte environment with gamete fusion. They interact with the oocyte cytoskeletal apparatus to form a functional pair of centrosomes and ultimately regulate pronuclear juxtaposition in preparation for the first cleavage. As a consequence, the fidelity of chromosome segregation during the first cell divisions depends on the function of sperm centrioles. Sperm DNA integrity is essential for embryo development and health. Damaged DNA does not impact on the sperm fertilization ability following ICSI. However, detrimental effects emerge at pre- and post-implantation stages. Sperm-specific epigenetic factors also play an active role in the regulation of embryonic development, as shown by correlations between reduced embryo morphological quality and incorrect chromatin packaging during spermiogenesis or abnormal methylation of sperm CpG islands. This functional landscape demonstrates that the contribution of the sperm to development goes far beyond its well-established role in fertilization. Clinical studies confirm this view and indicate sperm function as a crucial aspect of research to increase the efficacy of assisted reproduction treatments.
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24
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Van Opstal J, Fieuws S, Spiessens C, Soubry A. Male age interferes with embryo growth in IVF treatment. Hum Reprod 2021; 36:107-115. [PMID: 33164068 DOI: 10.1093/humrep/deaa256] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 09/02/2020] [Indexed: 12/23/2022] Open
Abstract
STUDY QUESTION Does male age affect embryo growth or quality in couples undergoing IVF treatment? SUMMARY ANSWER Advanced paternal age (APA) is negatively associated with the chance of an optimal eight-cell embryo on the third day of development. WHAT IS KNOWN ALREADY Literature shows that APA is associated with decreased sperm quality and fecundity. However, the effect of male age on embryo growth in an IVF setting remains inconclusive. Literature concerning male influences on IVF success is scarce and approaches used to analyse embryo outcomes differ by study. STUDY DESIGN, SIZE, DURATION This study was part of the longitudinal Epigenetic Legacy of Paternal Obesity (ELPO) study for which fathers and mothers were followed from pre-pregnancy until the birth of their child. Couples were recruited from April 2015 to September 2017. A total of 1057 embryos from 87 couples were studied. PARTICIPANTS/MATERIALS, SETTING, METHODS Dutch-speaking couples planning to undergo an IVF treatment were recruited at the Leuven University Fertility Center in Flanders, Belgium. Anthropometrics were documented and compared to the general Flemish population. Semen characteristics, pregnancy rates and the following embryo characteristics were recorded: number of blastomeres, symmetry and percentage fragmentation. Statistical modelling was applied taking into account correlation of within-cycle outcomes and use of multiple cycles per couple. MAIN RESULTS AND THE ROLE OF CHANCE We observed a significant inverse association between APA and a key determinant for scoring of embryo quality: older men were less likely to produce an embryo of eight blastomeres at Day 3, compared to younger fathers; odds ratio for the effect of 1 year equals 0.960 (95% CI: 0.930-0.991; P = 0.011). Our finding remained significant after adjusting for female age and male and female BMI. Degree of fragmentation and symmetry were not significantly related to male age. LIMITATIONS, REASONS FOR CAUTION Because of the study's small sample size and its monocentric nature, a larger study is warranted to confirm our results. In addition, distribution of BMI and level of education were not representative of the general Flemish population. Although we corrected for BMI status, we do not exclude that obesity may be one of the determinants of infertility in our study population. Furthermore, it is known from other European countries that a higher education eases access to fertility treatment. Hence, caution should be taken when interpreting our findings from a fertility setting to the general population. WIDER IMPLICATIONS OF THE FINDINGS We suggest a heightened need for future research into male age and its potential effects on embryo growth, embryo quality and ART outcomes. Clinical decision-making and preventative public health programmes would benefit from a better understanding of the role of men, carried forward by the Paternal Origins of Health and Disease (POHaD) paradigm. We hope the current finding will encourage others to examine the role of the sperm epigenome in embryo development according to paternal age. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by a research grant from KU Leuven University (OT/14/109). The authors declare no competing financial, professional or personal interests. TRIAL REGISTRATION NUMBER KU Leuven S57378 (ML11309), B322201523225.
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Affiliation(s)
- Jolien Van Opstal
- Epidemiology Research Center, Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven - University of Leuven, Leuven 3000, Belgium
| | - Steffen Fieuws
- L-Biostat, Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven - University of Leuven, Leuven 3000, Belgium
| | - Carl Spiessens
- Leuven University Fertility Clinic, KU Leuven - University of Leuven, Leuven 3000, Belgium
| | - Adelheid Soubry
- Epidemiology Research Center, Department of Public Health and Primary Care, Faculty of Medicine, KU Leuven - University of Leuven, Leuven 3000, Belgium
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25
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Halvaei I, Litzky J, Esfandiari N. Advanced paternal age: effects on sperm parameters, assisted reproduction outcomes and offspring health. Reprod Biol Endocrinol 2020; 18:110. [PMID: 33183337 PMCID: PMC7664076 DOI: 10.1186/s12958-020-00668-y] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 10/30/2020] [Indexed: 01/08/2023] Open
Abstract
Many factors, including postponement of marriage, increased life expectancy, and improved success with assisted reproductive technologies have been contributing to increased paternal age in developed nations. This increased average paternal age has led to concerns about adverse effects of advanced paternal age on sperm quality, assisted reproductive outcomes, and the health of the offspring conceived by older fathers. This review discusses the association between advanced paternal age and sperm parameters, assisted reproduction success rates, and offspring health.
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Affiliation(s)
- Iman Halvaei
- Department of Anatomical Sciences, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Julia Litzky
- Department of Pediatrics, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
| | - Navid Esfandiari
- Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont Medical Center, Larner College of Medicine, 111 Colchester Ave, Burlington, VT, 05401, USA.
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26
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Sterpu I, Pilo C, Koistinen IS, Lindqvist PG, Gemzell-Danielsson K, Itzel EW. Risk factors for poor neonatal outcome in pregnancies with decreased fetal movements. Acta Obstet Gynecol Scand 2020; 99:1014-1021. [PMID: 32072616 DOI: 10.1111/aogs.13827] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 02/11/2020] [Accepted: 02/16/2020] [Indexed: 11/30/2022]
Abstract
INTRODUCTION The incidence of Swedish stillbirths has varied little in the past 40 years, with a reported frequency of 400-450 stillbirths/y (approximately 4‰), despite increased information about fetal movement in the media and awareness among healthcare providers. The objectives of this project were to describe the outcome of pregnancies with reduced fetal movement in a Swedish context and to investigate factors associated with poor neonatal outcome in this group. MATERIAL AND METHODS A retrospective cohort study was performed at Soder Hospital, Stockholm, Sweden. All single pregnancies at the hospital from January 2016 to December 2017 presenting with reduced fetal movement after 22 gestational weeks were included in the study. A composite neonatal outcome was constructed: 5-minute Apgar score ≤7, arterial pH in the umbilical cord ≤7.10, transfer to neonatal care unit for further care or intrauterine fetal death. RESULTS For women seeking care for reduced fetal movement, the occurrence of composite poor neonatal outcome ranged from 6.2% to 18.4% within different groups. The highest risk for poor neonatal outcome (18.4%) was found in the group of women with a small-for-gestational-age fetus. Another high-risk group (12.8%) was the one comprising women with normal birthweight/large-for-gestational-age fetuses with an in vitro fertilization pregnancy. CONCLUSIONS The highest incidence of poor neonatal outcome among women with reduced fetal movement was found in the groups with small-for-gestational-age fetuses in nulliparous and multiparous women. A routine ultrasound assessment for fetal growth in third trimester is supposedly most efficient to identify undiagnosed small for gestational age.
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Affiliation(s)
- Irene Sterpu
- Department of Clinical Science and Education, Karolinska Institutet, Soder Hospital, Stockholm, Sweden.,Department of Obstetrics and Gynecology, Soder Hospital, Stockholm, Sweden
| | - Christina Pilo
- Department of Obstetrics and Gynecology, Soder Hospital, Stockholm, Sweden
| | - Ina S Koistinen
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Pelle G Lindqvist
- Department of Clinical Science and Education, Karolinska Institutet, Soder Hospital, Stockholm, Sweden.,Department of Obstetrics and Gynecology, Soder Hospital, Stockholm, Sweden
| | - Kristina Gemzell-Danielsson
- Department of Women's and Children's Health, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Eva W Itzel
- Department of Clinical Science and Education, Karolinska Institutet, Soder Hospital, Stockholm, Sweden.,Department of Obstetrics and Gynecology, Soder Hospital, Stockholm, Sweden
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27
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Carrasquillo RJ, Kohn TP, Cinnioglu C, Rubio C, Simon C, Ramasamy R, Al-Asmar N. Advanced paternal age does not affect embryo aneuploidy following blastocyst biopsy in egg donor cycles. J Assist Reprod Genet 2019; 36:2039-2045. [PMID: 31385121 DOI: 10.1007/s10815-019-01549-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 07/26/2019] [Indexed: 01/05/2023] Open
Abstract
PURPOSE To study the impact of advanced paternal age on embryo aneuploidy. METHODS This is a multicenter international retrospective case series of couples undergoing assisted reproduction via in vitro fertilization using donor eggs to control for maternal factors and preimplantation genetic testing for aneuploidy via next-generation sequencing at Igenomix reproductive testing centers. The main outcome measure was the prevalence of embryo aneuploidy in egg donor cycles. Semen analysis data was retrieved for a small subset of the male patients. RESULTS Data from 1202 IVF/ICSI egg donor cycles using ejaculated sperm (total 6934 embryos) evaluated using PGT-A between January 2016 and April 2018 in a global population across all Igenomix centers were included. No significant association was identified between advancing paternal age and the prevalence of embryo aneuploidy overall and when analyzing for each chromosome. There was also no significant association between advancing paternal age and specific aneuploid conditions (monosomy, trisomy, partial deletion/duplication) for all chromosomes in the genome. CONCLUSIONS This is the largest study of its kind in an international patient population to evaluate the impact of advancing paternal age on embryo aneuploidy. We conclude there is no specific effect of paternal age on the prevalence of embryo aneuploidy in the context of embryo biopsies from egg donor cycles.
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Affiliation(s)
- Robert J Carrasquillo
- Division of Urology, Beth Israel Deaconess Medical Center, 145 Rosemary Street, C-1, Needham, MA, 02494, USA. .,Igenomix, Valencia, Spain.
| | - Taylor P Kohn
- Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA
| | | | | | | | - Ranjith Ramasamy
- Department of Urology, University of Miami Health System, Miami, FL, USA
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28
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Mariappen U, Keane KN, Hinchliffe PM, Dhaliwal SS, Yovich JL. Neither male age nor semen parameters influence clinical pregnancy or live birth outcomes from IVF. Reprod Biol 2018; 18:324-329. [DOI: 10.1016/j.repbio.2018.11.003] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Revised: 11/08/2018] [Accepted: 11/10/2018] [Indexed: 12/14/2022]
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29
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Bartolacci A, Pagliardini L, Makieva S, Salonia A, Papaleo E, Viganò P. Abnormal sperm concentration and motility as well as advanced paternal age compromise early embryonic development but not pregnancy outcomes: a retrospective study of 1266 ICSI cycles. J Assist Reprod Genet 2018; 35:1897-1903. [PMID: 29995229 PMCID: PMC6150884 DOI: 10.1007/s10815-018-1256-8] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 06/29/2018] [Indexed: 10/28/2022] Open
Abstract
PURPOSE To investigate the effect of sperm concentration, motility and advanced paternal age on reproductive outcomes. METHODS A retrospective analysis of 1266 intracytoplasmic sperm injection (ICSI) cycles between 2013 and 2017. The cohort was divided into four groups according to semen concentration based on the WHO criteria (2010): group A (conc. <1 M/ml), group B (1 ≤ conc. <5 M/ml), group C (5 ≤ conc. < 15 M/ml) and the control group D (conc. ≥15 M/ml). The primary outcome investigated was the blastulation rate. Secondary outcomes were fertilization rate, top quality blastocyst formation rate and ongoing pregnancy rate. RESULTS After adjustment for maternal age and number of oocytes recovered, a significant difference was observed between group A and group D on the rate of fertilized oocytes [66.7 (40.0-80.0) vs 75.0 (57.1-90.2), adjusted p < 0.001] and the blastocyst formation rate [50.0 (33.3-66.3) vs 55.6 (40.0-75.0), adjusted p < 0.05]. However, the male factor did not affect the top quality blastocyst formation rate nor the ongoing pregnancy rate. Considering the age of the male partner as confounding factor, at the increase of each year of age, a reduction of 0.3% on the fertilization rate was observed but no other outcome was impacted. A negative correlation was also observed between sperm motility and fertilization rate in the group with a motility <5%. CONCLUSION Male factor infertility and advanced paternal age may compromise fertilization and blastulation rates but not top quality blastocyst formation rate or the establishment of pregnancy in ICSI cycles.
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Affiliation(s)
| | - Luca Pagliardini
- Division of Genetics and Cell Biology, Reproductive Sciences Laboratory, IRCCS Ospedale San Raffaele, Via Olgettina 58, 20132, Milan, Italy
| | - Sofia Makieva
- Division of Genetics and Cell Biology, Reproductive Sciences Laboratory, IRCCS Ospedale San Raffaele, Via Olgettina 58, 20132, Milan, Italy
| | - Andrea Salonia
- Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
- University Vita-Salute San Raffaele, Milan, Italy
| | - Enrico Papaleo
- Obstetrics and Gynaecology Department, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Paola Viganò
- Division of Genetics and Cell Biology, Reproductive Sciences Laboratory, IRCCS Ospedale San Raffaele, Via Olgettina 58, 20132, Milan, Italy.
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30
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Bertoncelli Tanaka M, Agarwal A, Esteves SC. Paternal age and assisted reproductive technology: problem solver or trouble maker? Panminerva Med 2018; 61:138-151. [PMID: 30021419 DOI: 10.23736/s0031-0808.18.03512-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
In our society, the number of couples with advanced reproductive age seeking fertility treatment is increasing steadily. While the negative effect of female age on assisted reproductive technology (ART) outcomes is well established, the impact of paternal age needs to be clarified. We reviewed the current literature to determine whether advanced paternal age affects the results of ART and the health of resulting offspring. We found that the published literature is overall supportive of a positive association between advanced paternal age (>40 years) and semen quality deterioration. However, the existing evidence does not corroborate nor discard the influence of advanced paternal age on ART outcomes. Similarly, the effect of paternal age on the health of ART offspring remains equivocal, although data from naturally-conceived children clearly indicates that advanced paternal age increases the frequency of genetic, neurodevelopmental, and psychiatric diseases in the progeny. Noteworthy, the current literature is limited and subjected to bias due to the impact of maternal age as a critical confounder. Health care providers should discuss with concerned couples the available options to counteract the possible negative influence of advanced paternal age on ART outcomes and health of resulting offspring. These include identification and treatment of underlying conditions with potential negative long-term effects on fertility, sperm freezing at a young age, and use of antioxidant supplements for men at risk of excessive oxidative stress. Aged male partner from couples undergoing ART, in particular men of 50 years and older, should consider use of preimplantation genetic testing as a means to detect embryo abnormalities and select euploid embryos for transfer to the uterine cavity.
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Affiliation(s)
| | - Ashok Agarwal
- American Center for Reproductive Medicine, Department of Urology, Cleveland Clinic, Cleveland, OH, USA
| | - Sandro C Esteves
- Division of Urology, Department of Surgery, University of Campinas (UNICAMP), Campinas, Brazil - .,Andrology and Human Reproduction Clinic ANDROFERT, Campinas, Brazil.,Faculty of Health, Aarhus University, Aarhus, Denmark
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31
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Abstract
PURPOSE OF REVIEW In many countries, the average age of paternity is rising. The negative effect of older age on fertility in women is well documented; however, less is known about the impact of paternal age on fecundity. In this review, we summarize the current knowledge of how paternal age affects semen parameters, reproductive success, and offspring health. RECENT FINDINGS Contemporary evidence confirms that aged men have worse semen parameters, including overall negative changes in sperm genetics. Reproductive outcomes with unassisted pregnancy tend to be worse with older fathers. While most current studies of assisted pregnancy do show a negative effect of paternal age, there are some conflicting results. Studies continue to show an overall increased risk of health problems, particularly neuropsychiatric conditions, in the offspring of older men. While men can often maintain fertility potential throughout a lifetime, increasing evidence indicates worsening of semen parameters, including sperm genetics, and potentially worse reproductive success. Older men should also be counseled on their offspring's possible increased risk of certain medical conditions.
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