A unique case of trichorionic quadruplet pregnancy after oocyte donation in a patient with Turner's syndrome

A 26-year old patient with a mosaic (45X/46XX) Turner's syndrome and secondary amenorrhea since the age of 19, was referred to the IVF unit for participation in oocyte donation program. After a complete work up including meticulous cardiological assessment, she had endometrial preparation with a high dose hormonal regimen, and transfer of three embryos derived from donated oocytes. An ongoing trichorionic quadruplet pregnancy was confirmed on ultrasound. The couple was offered fetal reduction to twins at 12 gestational weeks after consultation stressing the risks of a quadruplet pregnancy in general and especially in a patient with Turner's syndrome. No pregnancy or maternal complications were encountered and the patient delivered two healthy babies by lower segment cesarean section after spontaneous rupture of membranes at 36 gestational weeks.     

A successful pregnancy in a Turner syndrome with oocyte donation

Advances in reproductive medicine using oocyte donation have made it possible for women with Turner syndrome (TS) to achieve successful pregnancies. These pregnancies carry substantial fetal and maternal risks, with hypertensive disorders or pregnancy and fetal growth restriction common, and an increased risk of aortic dissection, sometimes fatal, for the woman. Careful prepregnancy assessment and fetal and maternal vigilance during pregnancy is a necessary prerequisite for a successful outcome. We present a case of a woman with Turner syndrome achieving a successful pregnancy from donor oocyte and review the relevant literature.     

Turner's syndrome and procreation. Ovarian function and Turner's syndrome

Ovarian failure is a typical feature in Turner's syndrome. The majority of follicles disappears prematurely after a normal determination of the ovary. This results from an accelerated loss of oocytes from the ovaries after the 18th week of fetal life or over a few postnatal years, usually before the onset of puberty. The cause and mechanism of this loss are unknown. X chromosomal anomaly due to deletions or haploinsufficiency of genes can explain the various degrees of ovarian failure. Spontaneous puberty occurs in 20-30% of Turner syndrome patients and their fertility rates vary from 5 to 10%. This indicates the possible presence and maturation of follicles in their ovaries in adolescence. In ovarian failure, the hormone replacement therapy (HRT) is necessary to achieve the development of normal female sexual characteristics, the self image or social functioning and to prevent osteoporosis. Pregnancy is now possible with oocyte donation. A careful cardiovascular follow-up is necessary. Cryoconservation represents one way for preserving the future fertility, but the optimal age of ovarian biopsy has to be studied.     

Turner's syndrome and pregnancy

After briefly summarizing Turner's syndrome, the authors reviewed several cases reported in the literature where pregnancy occurred in association with this syndrome. From this study it was revealed that pregnancy is exceptional in the course of Turner's syndrome since only 2 p. cent of women with this disorder conceive. Such an outcome may be explained by a reduced number of ovarian follicles. The poor prognosis when pregnancy does occur is represented by a 38 p. cent incidence of miscarriage, and an 18.4 p. cent rate of fetal malformations including a 6 p. cent rate of trisomy 21 (Down's syndrome). This finding requires that the patient be taken care of in a specialized department of obstetrics-gynecology, necessitates prenatal diagnosis and poses an ethical problem as to the obstetrical future of these patients.     

Shared oocyte donation: society's benefits

Objective: To assess the efficacy of oocyte donation when a cohort of oocytes is shared between two phenotypically matched recipients.

Design: A retrospective analysis of a program using shared anonymous oocyte donation.

Setting: Academic infertility center.

Patient(s): Recipient women with partial or complete ovarian failure; oocyte donors who have been properly screened.

Intervention(s): Each oocyte donor was phenotypically matched with two potential recipients. The cohort of donated oocytes were divided between these two recipients if eight or more mature oocytes were obtained at retrieval. Recipients underwent hormone replacement therapy consisting of down-regulation with a GnRH agonist, transdermal estradiol, and intramuscular progesterone in a dose determined by a previous preparatory cycle.

Main Outcome Measure(s): Pregnancy and delivery rates for all transfers originating from a cohort of oocytes obtained by retrieval of a single donor; pregnancy and delivery rates per recipient; rate of conversion of a shared donation cycle to a single recipient.

Result(s): A total of 249 donor cycles permitted 241 retrievals. Each recipient received 8.3 ± 3.5 oocytes per donation. There were 424 fresh ETs and 48 frozen ETs performed. For fresh ETs, clinical pregnancy and ongoing or delivery rates per recipient were 56.8% and 49.7%, respectively. For frozen ETs, these rates were 50% and 39.5%. Implantation rates were 31.8% and 26.1% for fresh and frozen ET, respectively. When analyzed per donor retrieval, clinical pregnancy and ongoing or delivery rates were 109.5% and 95.4%. These high pregnancy rates per donor reflect the numerous fresh and frozen ETs that can result from one donor’s retrieval. Conversion of a donation cycle from two recipients to one recipient occurred for 26 of 241 cycles (10.8%).

Conclusion(s): Shared anonymous oocyte donation provides a very high pregnancy rate per donor retrieval that is not achievable with unshared donation. In addition, there is a diminished risk exposure of donors per total completed recipient transfers. We support shared oocyte donation as the most efficient use of the precious resource of human oocytes.     

Complications of pregnancy after oocyte donation

Oocyte donation is a remarkably effective method of treatment even in difficult cases, which encourages couples. However the data in literature express an increased risk of complications in pregnancies particularly for older women. Maternal-fetal outcome is fortunately usually favorable. Medical teams must respect the autonomy of informed couples, but also be able to deny access to oocyte donation when age is exceeded or where there are risk factors.     

The evolution of oocyte donation in China

Objective

To review the experience with and clinical outcomes for recipients of embryos from oocytes donated under different regulatory standards in China. Initially, the oocytes were provided by one of the patient's consanguineous sisters. Then, the oocytes were obtained from another patient treated with assisted reproduction techniques (ART). Presently, oocytes thus produced are cryopreserved for at least 6 months before transfer.

Methods

The records from all women treated with ART at First Affiliated Hospital of Zhengzhou University since 2001 were reviewed and the pregnancy rates and clinical outcomes were determined for each of the 3 periods.

Results

In the second period, the mean implantation and clinical pregnancy rates were significantly higher for the 22 oocyte recipients than for their donors. In the third period, the rates for the 56 recipients were compared with the 78 other regular ART patients fertilized with their own oocytes. There were 40 live births for 32 of the recipients over 28 cycles, and the rates of implantation and clinical pregnancy were much higher for the recipients than for the other ART patients (P < 0.001).

Conclusion

Using freshly donated eggs yields a higher pregnancy rate but there is a risk of infectious disease. Using frozen oocytes can significantly decrease this risk but implantation rates are lower.     

Pregnancy rate in an oocyte donation program

Oocyte donation programs offer an alternative treatment for infertile women with ovarian failure or abnormal ovarian function. Seventeen cycles of in vitro fertilization and embryo transfer with donated oocytes were performed in 13 women, with a mean age of 34.8 years. The hormonal replacement therapy consisted of a fixed dose of oral estradiol valerate, 6 mg daily, and intramuscular progesterone in oil, 100 mg daily. Estrogen and progesterone were continued for 10 more weeks after embryo transfer if pregnancy was established. After 13 embryo transfers, 8 pregnancies were obtained, for a pregnancy rate per transfer of 61.5%. Today seven pregnancies are progressing normally, including one set of twins. This results suggest that an oocyte donation program using a fixed and simple hormonal replacement therapy is an adequate treatment for these infertile couples.