Partial hydatidiform mole following intracytoplasmic sperm injection and assisted zona hatching

A 35 year old women underwent her second cycle of in vitro fertilisation (IVF). She had an eight-year history of primary infertility due to endometriosis and male subfertility. The couple had undergone a cycle of gamete intrafallopian transfer six years previously, at which time only one oocyte was retrieved. The following year, she underwent a cycle of IVF when three oocytes were recovered, of which one fertilised and was replaced, without success. Her baseline investigations showed an follicle-stimulating hormone level of 5.7 u/L, luteinising hormone of 3.0 u/L and prolactin of 306 iu/L; her blood group was B Rhþve. The semen analysis showed a concentration of 80 10/mL, 11% normal forms (WHO criteria) and 17% progressive motility. Following these results, it was decided that intracytoplasmic sperm injection (ICSI) was the most appropriate procedure. Her partner’s karyotype was 46 XY, with no gross abnormalities. She was down-regulated with subcutaneous buserelin (Shire Pharmaceuticals, Hants, UK) using a standard longprotocol regimen from the midluteal phase of her previous menstrual cycle. After confirmation of satisfactory down-regulation by a transvaginal ultrasound scan, she underwent ovarian stimulation with 300 iu of human menopausal gonadotrophin (hMG, Menogon, Ferring, Kiel, Germany). After five days, a repeat ultrasound scan showed poor follicular development. The dose of hMG was therefore increased to 450 iu daily for a further seven days, at which time a repeat ultrasound scan showed four follicles between 18 and 25 mm in diameter. That evening, 5000 iu of human chorionic gonadotrophin (hCG) were given intramuscularly, and 36 hours later four oocytes were recovered transvaginally. Four hours after collection, the oocytes were denuded of their cumulus and coronal cells immediately prior to ICSI being performed. All four oocytes were assessed as being at metaphase II and were thus injected. The semen analysis on that day showed a volume of 5 mL, a concentration of 60 10/mL, 32% normal morphology and 40% progressive motility. The sample was prepared using a conventional swim-up technique. Eighteen hours following the ICSI procedure, the four oocytes were examined for evidence of fertilisation. One oocyte contained two clear pronuclei and was assumed to have fertilised ‘normally’. One oocyte contained only one pronucleus, although two polar bodies were observed. The remaining two oocytes showed no evidence of fertilisation. These three oocytes were allowed to perish. After a further 24 hours, the normally fertilised oocyte had undergone two cleavage divisions to reach the four-cell stage. No evidence of blastomere fragmentation or irregularity was observed. Before transfer to the woman, this embryo was subjected to assisted zona hatching using acid tyrose solution, as first described by Cohen et al.. Luteal support was given in the form of progesterone pessaries (Cyclogest, Shire Pharmaceuticals) begun the day before embryo transfer. Thirteen days after transfer, the woman reported moderate vaginal bleeding and did not undergo pregnancy testing. After a further interval of five weeks, further menstrual bleeding had not occurred. She performed a urinary pregnancy test, which was positive. A transvaginal ultrasound scan showed a thickened endometrium of 18 mm with no obvious adnexal masses and no free fluid. A serum h-hCG showed a level of greater than 15,000 iu/mL, and in view of this a laparoscopy was performed, which excluded ectopic pregnancy. The repeat h-hCG concentration one week later was greater than 15,000 iu/mL and a transvaginal ultrasound scan showed a cystic endometrium, 24 mm in thickness. A provisional diagnosis of trophoblastic disease was made. The woman underwent suction evacuation of the uterus the following day. Histologic examination showed hydropic chorionic villi with trophoblastic inclusions and mild hyperplasia; a chorionic plate was identified, confirming a partial mole. Flow cytometry showed that the mole was diploid. BJOG: an International Journal of Obstetrics and Gynaecology August 2002, Vol. 109, pp. 964–966