Should we perform oocyte accumulation to preserve fertility in women with Turner syndrome (TS)?

The oocyte cryopreservation strategy is not well adapted for all TS women as their combination of high basal FSH with low basal AMH and low percentage of 46,XX cells in the karyotype significantly reduces the chances of freezing sufficient mature oocytes for fertility preservation.

An oocyte cryopreservation strategy requiring numerous stimulation cycles is needed to preserve fertility in TS women, to compensate for the low ovarian response, the possible oocyte genetic alterations, the reduced endometrial receptivity, and the increased rate of miscarriage, observed in this specific population. The validation of reliable predictive biomarkers of ovarian response to hormonal stimulation in TS patients is necessary to help practitioners and patients choose the best-personalized fertility preservation strategy.

A retrospective bicentric study was performed from 1 January 2011 to 1 January 2023. Clinical and biological data from all TS women who have received from ovarian stimulation for fertility preservation were collected. A systematic review of the current literature on oocyte retrieval outcomes after ovarian stimulation in TS women was also performed (PROSPERO registration number: CRD42022362352).

A total of 14 TS women who had undergone ovarian stimulation for fertility preservation were included, representing the largest cohort of TS patients published to date (n = 14 patients, 24 cycles). The systematic review of the literature identified 34 additional TS patients with 47 oocyte retrieval outcomes after ovarian stimulation in 14 publications (n = 48 patients, n = 71 cycles in total).

The number of cryopreserved mature oocytes on the first cycle for TS patients was low (4.0 ± 3.7). Oocyte accumulation was systematically proposed to increase fertility potential and was accepted by 50% (7/14) of patients (2.4 ± 0.5 cycles), leading to an improved total number of 10.9 ± 7.2 cryopreserved mature oocytes per patient. In the group who refused the oocyte accumulation strategy, only one patient exceeded the threshold of 10 mature cryopreserved oocytes. In contrast, 57.1% (4/7) and 42.9% (3/7) of patients who have underwent the oocyte accumulation strategy reached the threshold of 10 and 15 mature cryopreserved oocytes, respectively (OR = 8 (0.6; 107.0), P = 0.12; OR= 11 (0.5; 282.1), P = 0.13). By analyzing all the data published to date and combining it with our data (n = 48 patients, n = 71 cycles), low basal FSH and high AMH concentrations as well as a higher percentage of 46,XX cells in the karyotype were significantly associated with a higher number of cryopreserved oocytes after the first cycle. Moreover, the combination of low basal FSH concentration (<5.9 IU/l), high AMH concentration (>1.13 ng/ml), and the presence of 46,XX cells (>1%) was significantly predictive of obtaining at least six cryopreserved oocytes in the first cycle, representing objective criteria for identifying patients with real chances of preserving an adequate fertility potential by oocyte cryopreservation.

Our results should be analyzed with caution, as the optimal oocyte number needed for successful live birth in TS patients is still unknown due to the low number of reports their oocyte use in the literature to date.

TS patients should benefit from relevant clinical evaluation, genetic counseling and psychological support to make an informed choice regarding their fertility preservation technique, as numerous stimulation cycles would be necessary to preserve a high number of oocytes.

This research received no external funding. The authors declare no conflict of interest.

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Coexistence of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, Graves' disease and 47, XXX is rare. We report a case of a 25-year-old woman presented with masculine appearance, hirsutism and enlarged clitoris. Lab tests showed elevated serum 17 hydroxyprogesterone, testosterone, dehydroepiandrosterone. Gene test revealed heterozygous gene mutation in CYP21A2:NM_000500:exon4:c.518 T > A, NM_000500:exon8:c.C1024T. Karyotype analysis showed 47, XXX. After prednisone replacement and antithyroid therapy, she got a normal menstruation and normal level of testosterone. These findings demonstrate that patients with abnormal chromosome are likely to combine 21-hydroxylase deficiency (21-OHD), thus karyotyping test should not be neglected for those who have been already diagnosed as 21-OHD. Additionally, chromosomal abnormality such as 47, XXX and Turner syndrome had susceptibility to develop autoimmune thyroid disease because a gene on X chromosome may be responsible for the occurrence of autoimmune thyroid disease. Moreover, both 21-OHD and Graves' disease (GD) can lead to high level of testosterone, thus we should keep in mind to test chromosome and thyroid function in 21-OHD patients to avoid misdiagnose or missed diagnosis. To the best of our knowledge, this is the first report of simple virilizing (SV) 21-OHD patient combined with 47, XXX and Graves disease.

A 24-years-old female of Han ethnicity was admitted to the endocrinology department complaining of absence of menses for half a year. The patient didn't noticed her enlarged clitoris until she was 17 years old. Her menarche was 16 years old and the final height was 163 centimeter. She was diagnosed with GD 2 months before admission to our hospital due to palpitation, heat intolerance, muscle weakness.

The patient was diagnosed with SV 21-OHD, Graves disease and 47, XXX.

At first, the patient was given 10 mg methimazole twice a day as well as 5 mg predisone in the morning and 2.5 mg in the evening. After a year of regular medication and reexamination, she got a regular menstruation and thyroid function and now is taking 2.5 mg prednisone twice a day.

The patient got a regular menstruation and thyroid function. Laboratory results showed: testosterone declined to 0.1nmol/L (0.1-1.67nmol/L) and 17 hydroxyprogesterone get back to normal level: 1.01ng/ml (0.30-2.34ng/mL). However, her enlarged clitoris has not narrowed.

Patients with abnormal chromosome are likely to combine 21-OHD, thus karyotyping test should not be neglected for those who have been already diagnosed as 21-OHD. Additionally, chromosomal abnormality such as 47, XXX and Turner syndrome had susceptibility to develop autoimmune thyroid disease because a gene on X chromosome may be responsible for the occurrence of autoimmune thyroid disease. Moreover, both 21-OHD and GD can lead to high level of testosterone, thus we should keep in mind to test chromosome and thyroid function in 21-OHD patients to avoid misdiagnose or missed diagnosis. To the best of our knowledge, this is the first report of SV 21-OHD patient combined with 47, XXX and Graves disease.

Turner's syndrome (TS) is depicted as a total or partial absence of one X chromosome that results in ovarian dysgenesis. Chances of spontaneous pregnancy in TS are rare and the outcome of the pregnancies is known to be poor with an increased risk of miscarriage and stillbirths. Our aim is to evaluate reproductive and obstetric outcomes of natural conception and in-vitro fertilization (IVF) cycles in mosaic TS patients.

A total of 22 mosaic TS cases (seventeen 45,X/46,XX and five 45,X/46,XX/47,XXX karyotypes) were evaluated.

Live birth and abortion rates were found as 32.7 % and 67.3 %, respectively in 52 pregnancies. Implantation, clinical pregnancy and take home baby rates were detected as 3.7 %, 8.6 % and 5.7 %, respectively per IVF cycle as a result of 35 cycles. Fecundability analysis revealed that 5 % of the cases experienced first pregnancy within 6 months and 8 % within the first 2 years. Mosaicism ratio did not have an effect on the time to the first pregnancy (p = .149).

Only a small proportion of the mosaic TS patients conceive in the first 2 years of the marriage. Age of menarche and age of marriage appear not to have any impact on the chance of conceiving. Mosaic TS cases should counseled about the low odds of pregnancy and high miscarriage rates.

A combination of Turner syndrome (TS) and classical congenital adrenal hyperplasia (CAH) is rare. A one-day-old newborn was referred to our hospital with ambiguous genitalia. The parents were third-degree relatives. The infant's weight was 3350g (50-75p), and the head circumference was 34.5cm (50p). The gonads were nonpalpable. Presence of a 3 cm phallus, one urogenital opening into the perineum, and incomplete labial fusion were identified. Laboratory tests revealed a classical type of CAH due to 21-hydroxylase deficiency. Karyotyping revealed a 45X0(35)/46XX(22) pattern with negative sex-determining region Y (SRY) on gene analysis. At the most recent follow-up visit, the patient appeared to be in good health - her height was 70.4 cm [-1.5 standard deviation (SD)] and her weight was 9.8 kg (0.3 SD). She was receiving hydrocortisone in a dose of 10 mg/m²/day, fludrocortisone acetate in a dose of 0.075 mg/day, and oral salt of 1 g/day. System examinations were normal. The patient's electrolyte levels were found to be normal and she was in good metabolic control. The findings of this patient demonstrate that routine karyotyping during investigation of patients with sexual differentiation disorders can reveal TS. Additionally, signs of virilism should always be investigated at diagnosis or during physical examinations for follow-up of TS cases. SRY analysis should be performed primarily when signs of virilism are observed. CAH should also be considered in patients with negative SRY.

Turner's syndrome is characterized by an ovarian failure which occurs in most cases before puberty and leads to infertility. In less than 10% of women with Turner syndrome, puberty may occur and spontaneous pregnancies is possible but with a high risk of fetal loss, chromosomal and congenital abnormalities. We present the case of a 33-year-old woman with a mosaic Turner's syndrome karyotype 45,X/47,XXX who conceived spontaneously and had two successful pregnancies. Short stature was the only manifestation of Turner's syndrome. In the present report, we reviewed the available literature on the fertility of women with Turner's syndrome and the phenotypic effects of mosaicism for a 47,XXX cell line in Turner's syndrome.

To describe a case of Goldenhar syndrome in a couple receiving donated oocytes in an 'egg sharing' IVF cycle where the recipient of donor oocytes had Turner syndrome, hypothyroidism and gestational diabetes.

Case report

Child born to oocyte recipient with Goldenhar syndrome

We believe this is the first reported case of a child born with Goldenhar syndrome following use of donated oocytes in IVF by a woman with Turner syndrome, hypothyroidism and gestational diabetes.

Women with Turner syndrome (TS) are at risk of premature ovarian failure. The objective of this retrospective study was to identify patients with TS who could be potential candidates for fertility preservation and to determine their present reproductive and fertility status. Criteria for fertility preservation included: (i) spontaneous menarche; (ii) confirmation by ultrasound examination of the presence of at least one normal ovary; and (iii) serum FSH concentrations below 40 IU/l. Using the Montreal Children's Hospital Cytogenetic Database from 1990 to 2006, 28 patients with complete or partial absence of one X chromosome were identified: 13 (46%) were 45,X; nine (32%) had mosaic karyotypes; and six (21%) had karyotypes containing isochromosome or ring X chromosome. Six patients (21%) had spontaneous pubertal development and four (14%) were identified as potential candidates for fertility preservation. One underwent an ovarian stimulation protocol of gonadotrophin-releasing hormone agonist down-regulation followed by recombinant FSH and human menopausal gonadotrophin stimulation. Two metaphase-II-stage oocytes were aspirated and vitrified using the McGill Cryoleaf vitrification system. Another patient conceived spontaneously at the age of 24 years. In conclusion, fertility preservation may not be feasible for most patients with TS. However, after careful consideration of increased pregnancy-associated risks, fertility preservation may be offered to young females with mosaic TS.

This paper reviews literature about oocyte donation for patients with Turner's syndrome and reports the experience of our center. Before contemplating pregnancy, it is essential to perform a careful evaluation of the cardiovascular system, the renal system, the thyroid status and the glucose tolerance. Different studies have reported a suboptimal response of the endometrium of women with Turner's syndrome to oestrogen therapy, and suggested that higher doses of estrogens may be necessary to achieve appropriate endometrial preparation. Pregnancy rate per transfer following oocyte donation is around 30% for patients with Turner's syndrome, comparable to the one observed for patients with other conditions requiring oocyte donation. Miscarriage rate is however higher (40-50%) after oocyte donation in Turner's syndrome, and could be related to the presence of a hypoplastic uterus along with hypovascularization. During pregnancy, cardiovascular complications are potentially the most severe, such as the exacerbation of a preexisting hypertension and the dissection of aortic aneurysms. There is a high rate of Caesarean section among Turner's syndrome patients, the main reason being fetopelvic disproportion. Regarding the increased obstetrical risks in Turner's syndrome patients, the selective transfer of one embryo should ideally be performed in order to avoid additional risks associated with multiple pregnancies. In our center, 9 patients with a Turner's syndrome had 15 cycles of oocyte donation. Five pregnancies were obtained among which three were evolutive. The outcome of oocyte donation cycles were comparable for patients with a Turner's syndrome and for patients with other indications of oocyte donation.