Oocyte donation using immature oocytes from a normal ovulatory woman.

Abstract

Oocyte donation is a well-established treatment for some infertile patients. The main problem with an oocyte donation program is the limited source of donors. The discomfort and risks associated with ovarian stimulation and oocyte retrieval limit the availability of donors. Recovery of immature oocytes followed by in vitro maturation (IVM) is a potential alternative of infertility treatment. This technique saves tedious ovarian stimulation and may greatly improve a woman's willingness to be an oocyte donor. Pregnancies resulting from immature oocyte donation of Cesarean section or PCOS women have been reported (1), although the pregnancy rates were very low. Recent reports by Chian et al. proposed that by giving human chorionic gonadotropin (HCG) before immature oocyte recovery from polycystic ovary syndrome (PCOS) women, the pregnancy rate could be significantly improved (2). We reported here the first case of pregnancy resulting from immature oocyte donation, after priming with HCG, from a normal ovulatory woman with polycystic appearing ovaries. Unfortunately, this pregnancy ended up as an ectopic pregnancy. A 44-year-old woman presented with secondary infertility due to a tubal factor. Oocyte donation was suggested because of a poor response in two previous IVF cycles. Her 36-year-old sister, gravida 3 para 2, with a regular menstrual cycle, consented to be her oocyte donor. The basic hormone study of the donor including prolactin, testosterone, progesterone, day 3 follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were all within normal limits. Ultrasound of the potential donor showed multiple small follicles without any drug. After desensitizing with buserelin (Supremon, Hoechst, Frankfurt, Germany), the recipient took conjugated estrogen (Premarin, 0.625 mg, Wyeth-Ayerst, Philadelphia, PA, USA) one tablet tid to prepare the endometrium. On the donor's cycle day 7, ultrasound revealed 18 follicles smaller than 10 mm. Ten thousand IU of HCG (Profasi, Serono, Welwyn Garden City, UK) was given, and oocyte retrieval was performed 36 hr later to obtain 16 oocytes. The oocytes were cultured in maturation medium at 37 °C in an atmosphere of 5% CO2 in air. The maturation medium consisted of TCM199 medium (Sigma Chemical Co., St Louis, MO, USA) supplemented with 20% patient serum, 75 mIU/ml HMG (Humegon; NV Organon, Oss, the Netherlands), and 0.2 mM pyruvate (Sigma Chemical Co.). After 48 hr, eight oocytes reached metaphase II (MII), and were fertilized by introcytoplasmic sperm injection (ICSI). Seven oocytes were fertilized, and five embryos were transferred after 3 days of culture. Assisted hatching was done before embryo replacement. Unfortunately, the patient was not able to become pregnant. Two months later, they presented for another course of oocyte donation. The recipient was suppressed as described in the previous cycle. On the donor's cycle day 9, ultrasound revealed 14 follicles smaller than 10 mm. Oocyte retrieval was done 36 hr after HCG injection to obtain seven immature oocytes. Five oocytes were matured after 48 hr of culture, and ICSI was performed to give four 2-pronucleated oocytes (2PN). Four embryos were transferred on day 3. The recipient was found pregnant; however, it ended up as a left tubal pregnancy. This case demonstrates that immature oocytes from normal ovulatory women can be a potential source of oocyte donation. The simplicity of the in vitro maturation (IVM) protocol greatly increases a woman's willingness to donate her oocytes. Since Cha et al. first reported pregnancy and delivery from immature oocytes derived from an oophorectomy specimen (3), several reports have been published, including immature oocytes from PCOS patients (4). However, the pregnancy rate is very low, and only limited to case reports. Recently, Chian et al. proposed that HCG priming, i.e. 10 000 IU HCG injection followed by oocyte retrieval 36 hr later, significantly increased the maturation rate and pregnancy rate with immature oocytes from PCOS patients (2). A pregnancy rate of 40% has been reported. PCOS patients are attractive candidates for IVM because they have many arrested small follicles. However, we do not think they are good candidates for oocyte donation. The oocyte quality in PCOS women is compromised compared with oocytes from regular cycling women because of abnormal hormone milieu. Barnes et al. demonstrated that immature oocytes recovered from regular cycling women matured and fertilized at significantly higher rates than irregular cycling and anovulatory women (4). Furthermore, women with PCOS have other problems such as acne, hirsutism, obesity, cardiovascular diseases, and insulin resistance besides anovulation, and there is concern about a possible transmission of the syndrome to the next generation. In conclusion, recovery of immature oocytes from unstimulated ovaries followed by IVM is a feasible alternative for oocyte donation. Women with polycystic appearing ovaries, who comprise 25% of the adult female population (5), can be a new source for oocyte donation.