Vitrification of oocytes recovered without ovarian stimulation and matured in vitro.
First birth achieved after fertility preservation using vitrification of in vitro matured oocytes in a woman with breast cancer
The question of fertility preservation (FP) in young cancer patients has become a major issue. Although many techniques have been developed, vitrification of fertilized or unfertilized oocytes recovered after controlled ovarian stimulation before cancer therapy currently represents the most established and efficient method for preserving female fertility. When ovarian stimulation is unfeasible or contraindicated, ovarian tissue cryopreservation or oocyte/embryo vitrification after in vitro maturation (IVM) of oocytes recovered from small antral follicles may constitute alternative options. The place of IVM in the strategy of female FP has recently been the subject of debate. We herein report the case of a 29-year-old nulligravida woman diagnosed with left grade III invasive ductal carcinoma. Tumor was positive for both estrogen and progesterone receptors and negative for Her2 overexpression. After left tumorectomy with sentinel node biopsy (1N+/4), adjuvant chemotherapy was scheduled 3 weeks later.
Before FP counseling, on cycle day 16, a transvaginal ultrasound scan revealed 17 small antral follicles (2–9 mm in diameter) and a left corpus luteum. Serum Anti-Müllerian hormone levels were at 2.01 ng/ml. Due to the contraindication to ovarian stimulation for oncologic purposes (N+ disease), the patient was offered oocyte vitrification after IVM in combination with ovarian tissue cryopreservation. She rejected the laparoscopic option and opted for IVM only. One IVM cycle (Figure 1) was scheduled as an emergency on cycle day 22. Briefly, seven immature oocytes were retrieved under transvaginal ultrasound guidance. Oocyte–cumulus complexes were matured in IVM medium (Origio, Versailles, France), supplemented with the patient’s own serum, as well as with 0.75 UI/ml of follicle-stimulating hormone and 0.11 UI/ml of human chorionic gonadotropin (Menopur®, Ferring) for 24 h. Thereafter, oocytes were denuded of cumulus cells with hyaluronidase and checked for maturity at 24 and 48 h. Following 48 h of IVM, a total of six metaphase II oocytes were vitrified.
Five years later, the patient experienced infertility for 1 year. Pregnancy was authorized by the oncologic team, but the patient was advised to avoid ovarian stimulation. Therefore, the multidisciplinary decision was the reutilization of cryopreserved oocytes as a first choice.
Endometrial preparation was obtained using hormonal substitution through the administration of estradiol-17β (Provamès®, Sanofi Aventis, Gentilly, France), 6 mg/day, orally. On the 14th day of estradiol intake, a transvaginal ultrasound scan was carried out to confirm that endometrial thickness was >8 mm. Then, micronized progesterone administration (Progestan®, Besins Healthcare, Paris, France), 800 mg/day vaginally, was started in combination with estradiol-17β treatment. The six oocytes were thawed, and all of them survived the procedure, allowing insemination by intracytoplasmic sperm injection. Five zygotes were obtained, and one Cleavage-stage embryo was transferred into the uterus after 3 days of progesterone intake. The patient became pregnant and uneventfully delivered a healthy baby boy at term.
We report the first live birth achieved using vitrification of in vitro oocytes matured for FP in a woman with cancer. This approach was based on the impossibility of considering ovarian stimulation for oncologic considerations. Therefore, IVM should be considered as a viable and efficient option in the strategy of female FP.