Natural cycle IVF can be a successful treatment alternative for patients with low ovarian reserve

Abstract

Objective: In general, patients with low ovarian reserve are difficult to manage and have a relatively poor prognosis. Using traditional stimulation protocols like the long GnRH agonist protocol or the GnRH antagonist protocol in these patients often results in low ovarian response and poor pregnancy rates. In natural menstrual cycles without ovarian stimulation, every month the female body naturally selects the best possible oocyte for ovulation. Nevertheless, hormonal changes due to ovarian insufficiency can influence and change the individual menstrual cycle pattern of each patient over the time, which may result in difficulties to conceive naturally. We observed the menstrual cycle pattern of patients with low ovarian reserve in order to distinguish different stages of ovarian insufficiency. Once we were able to describe the different stages, we developed new treatment approaches for each patient group based on Natural Cycle IVF. Methods: In 2012, the menstrual cycle pattern of 10 patients with AMH <1.0 nmol/L were observed. Patients were 22 - 42 years old (average 39.3). Blood samples were drawn to determine AMH, FSH, LH, E2 and transvaginal ultrasound scans were performed on different days of the cycle. Depending on the cycle pattern of each patient, we offered individualized treatment approaches based on Natural Cycle IVF using Clomifen citrate to control ovulation, GnRH agonists to induce ovulation and either Ethinyl-Estradiol or combined oral contraceptive pills to regulate the cycle. Embryos were vitrified in day 2 stages and transferred later in artificial cycles. Patients were informed about off label use of the medication and informed consents were signed. Results: Based on our observation, we could describe four different stages of ovarian insufficiency. We were able to perform oocyte retrievals and embryo transfers in all 10 patients. A total of 33 natural cycles were initiated. Premature ovulation occurred in 3 cycles (9.0%) and no retrieval was attempted. Among the attempted 30 oocyte retrievals, 21 (70.0%) were successful. Out of those 21 oocytes 11 (36.6% per retrieval) were mature and 10 (33.3% per retrieval) were immature. ICSI resulted in 8 fertilizations (72.7% per mature oocyte). Out of 8 transfers, 3 (37.5%) resulted in biochemical pregnancy. Two patients delivered (25.0%), one patient had a miscarriage at 8 weeks of pregnancy. Conclusion: Our experience shows that ovulation can successfully be controlled by the use of Clomiphene citrate and does not necessarily require GnRH analogues for pituitary suppression. This knowledge opens new space for development of alternative protocols respecting the patients' own physiology with no need for heavy stimulation. Patients with ovarian insufficiency may benefit from this approach, which can be offered before referring them to egg donation.