Abstract
BackgroundLetrozole is widely employed as ovulation induction agent in women with PCOS, but its use in mild stimulation (MS) protocols for IVF is limited. Aim of the present study was to evaluate the feasibility of a MS protocol with letrozole plus hMG in non-obese PCOS women undergoing IVF after a metformin pre-treatment.MethodsWe retrospectively evaluated the data of 125 non-obese PCOS undergoing MS with letrozole plus hMG, 150 IU as starting dose, (group 1, N = 80) compared to those undergoing a conventional IVF stimulation protocols (CS) (group 2, N = 45) prior to IVF. All patients had received metformin extended release 1200–2000 mg daily for three to six months before IVF. GnRH antagonist was administered in both groups when the leading follicles reached 14 mm.ResultsBoth groups were comparable for age, BMI and ovarian reserve markers. Both groups showed lower than expected AFC and AMH values as a consequence of metformin pre-treatment. Letrozole-treated patients required a significantly lower amount of gonadotropins units (p < 0.0001), and showed significantly lower day 5, day 8 and hCG day E2 levels compared to patients undergoing the CS protocol (p < 0.0001, p < 0.0001 and p = 0.001 respectively). The oocyte yield, in terms of total (6, IQR 3, vs 6, IQR 4 respectively,) and MII oocytes (5, IQR 3, vs 5, IQR 3, respectively) number, did not differ among groups; the number of total (3, IQR 2, vs 3, IQR 1 respectively) and good quality embryos (2, IQR1 vs 2, IQR 1,5 respectively) obtained was comparable as well in the two groups. The number of fresh transfers was significantly higher in group 1 compared to group 2 (80% vs 60%, p = 0.016). A trend for higher cumulative clinical pregnancy rate was found in women undergoing MS compared to CS (42.5%vs 24,4%, p = 0.044), but the study was not powered to detect this difference.ConclusionsThe present study suggests that the use of letrozole as adjuvant treatment to MS protocols for IVF may be an effective alternative to CS protocols for non-obese PCOS patients pre-treated with metformin, as it provides comparable IVF outcome without requiring high FSH dose, and avoiding supraphysiological estradiol levels.
Highlights
Letrozole is widely employed as ovulation induction agent in women with Polycystic ovarian syndrome (PCOS), but its use in mild stimulation (MS) protocols for in vitro fertilization (IVF) is limited
Patients Among all infertile women with PCOS referred to our Reproductive Unit for couple infertility from January 2014 to December 2017, we retrospectively evaluated those who satisfied the following entry criteria: having received a MS protocol with letrozole plus human menopausal gonadotropin (hMG) or a conventional IVF stimulation protocols (CS) with hMG alone in a gonadotropin releasing hormone (GnRH) antagonist co-treated IVF/Intracytoplasmic sperm injection (ICSI) cycle, and having received metformin in the preceding three to six months
The use of letrozole did not impact on progesterone levels and on endometrial thickness, both resulting comparable among groups; on the other hand, MS with letrozole resulted in an higher percentage of fresh cycles compared to the CS protocol (80 vs 60%, p = 0.016)
Summary
Letrozole is widely employed as ovulation induction agent in women with PCOS, but its use in mild stimulation (MS) protocols for IVF is limited. It is intended to offer a safer, cost-effective, patient-friendly protocol in which the risks of treatment are minimized [2], and in which the benefits are grossly comparable to those provided by conventional IVF stimulation protocols (CS) Relevant to this point, studies have demonstrated that increasing the FSH may not improve the IVF outcome, since there is no direct relationship between FSH dose and embryo quality [3], and the number of euploid embryos don’t differ when MS or conventional ovarian stimulation protocols are employed [4]. As far as we could know, no study has been drawn to evaluate its use in infertile women with polycystic ovary syndrome undergoing IVF
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