Re-implantation of cryopreserved ovarian cortex resulting in restoration of ovarian function, natural conception and successful pregnancy after haematopoietic stem cell transplantation for Wilms tumour

Abstract

With the improvement of long-term cancer survival rates, growing numbers of female survivors are suffering from treatment-related premature ovarian insufficiency (POI). Although pre-treatment embryo and oocyte storage are effective fertility preservation strategies, they are not possible for pre-pubertal girls or women who cannot delay treatment. In these cases, the only available treatment option is ovarian cortex cryopreservation and subsequent re-implantation. A 32-year-old woman had ovarian cortex cryopreserved 10 years previously before commencing high-dose chemotherapy and undergoing a haematopoietic stem cell transplant for recurrent adult Wilms tumour, which resulted in POI. She underwent laparoscopic orthotopic transplantation of cryopreserved ovarian cortex to the original site of biopsy on the left ovary. She ovulated at 15 and 29 weeks post-re-implantation with AMH detectable, then rising, from 21 weeks, and conceived naturally following the second ovulation. The pregnancy was uncomplicated and a healthy male infant was born by elective Caesarean section at 36⁺⁴ weeks gestation. This is the first report of ovarian cortex re-implantation in the UK. Despite the patient receiving low-risk chemotherapy prior to cryopreservation and the prolonged tissue storage duration, the re-implantation resulted in rapid restoration of ovarian function and natural conception with successful pregnancy.

Keywords: AMH; Fertility preservation; Ovarian cortex re-implantation; Premature ovarian insufficiency.

Fig. 1

Biopsy of ovarian cortex removed at the time of ovarian cortex cryopreservation demonstrating a single primordial follicle with two nucleoli surrounded by normal ovarian stroma. The patient had already received non-sterilising chemotherapy prior to this biopsy

Fig. 2

Laparoscopic orthotopic ovarian cortex re-implantation. a The atrophic native left ovary with scarring from previous ovarian cortical biopsy clearly visible. b A longitudinal incision was made along the left ovary resulting in a vascular surface. c Eight pieces of ovarian cortex were placed inside the native left ovary and adhered with fibrin sealant

Fig. 3

Serum hormones were measured following re-implantation, with day 0 being the day of re-implantation. a Serum gonadotrophin (follicle stimulating hormone (FSH), luteinising hormone (LH) and estradiol (E₂) levels. The grey boxes illustrate time periods on hormone replacement therapy (HRT). Corresponding progesterone rises occurred following the two E₂ peaks denoted by black arrows, confirming ovulation. b Serum anti-Mϋllerian hormone (AMH) levels rose steadily from 21 weeks post-re-implantation

Fig. 4

Transvaginal ultrasound scan images post-re-implantation. a Two antral follicles on the left ovary seen at 29 weeks postoperatively. The larger follicle had a mean diameter of 15 mm and ovulation was confirmed by a progesterone rise 1 week later. b Longitudinal view of the uterus at 29 weeks post-re-implantation demonstrating an endometrial thickness of 7.9 mm. c Single viable intrauterine pregnancy at 7⁺³ weeks gestation by crown-rump length (CRL) measurement (white arrow). The yolk sac is denoted by the black arrow. A corpus luteum was seen on the left ovary