Mild ovarian stimulation with letrozole plus fixed dose human menopausal gonadotropin prior to IVF/ICSI for infertile non-obese women with polycystic ovarian syndrome being pre-treated with metformin: a pilot study

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.

The Effect of Low Carbohydrate Diet on Polycystic Ovary Syndrome: A Meta-Analysis of Randomized Controlled Trials

“…Additionally, it is also conceivable to use metformin and/or inositol to increase insulin sensitivity, and to induce ovulation with letrozole or a selective estrogen receptor modulator (SERM) [3]. Possibly, laparoscopic ovarian diathermy (LOD) or low dose FSH stimulation could be introduced in the case of SERM and/or letrozole resistance [31]. However, the abovementioned treatments promoting ovulation may lead to an increased risk of ovarian hyperstimulation syndrome (OHSS) in PCOS patients, in particular, those with high levels of anti-Müllerian hormone (AMH) [23, 30, 32].…”

“…However, the abovementioned treatments promoting ovulation may lead to an increased risk of ovarian hyperstimulation syndrome (OHSS) in PCOS patients, in particular, those with high levels of anti-Müllerian hormone (AMH) [23, 30, 32]. It has been demonstrated that PCOS patients with high AMH levels are not only insensitive to the therapeutic effect of ovulation induction but also have a greater risk of OHSS [31–34].…”

Anti-Müllerian Hormone (AMH) is A Good Predictor for Ongoing Pregnancy in Women Undergoing IVF/ICSI in Antagonist Cycles

“…It has always been difficult to keep the balance between having a high pregnancy and minimizing OHSS. Patients with anovulation have high AMH and tend to have many follicles on stimulation, but they may also have a low response if stimulated with an inadequate dose of FSH [20][21][22]. In our study we could show that patients with high AMH, even some of them, do not have many oocytes nevertheless, had better pregnancy rate in the first cycle regardless of age.…”

The key factors affecting cumulative live birth rate after single oocyte retrieved in women during IVF/ICSI-ET: a retrospective analysis of 1380 PCOS patients

“…Compared with standard GnRHagonist protocol, it related to lower OHSS rate, but had higher cycle cancellation rate. CLBR after repeated ovulation was not affected, and was mostly used for the decline of ovarian function [22][23][24]. In summary, the Prolonged GnRH-agonist protocol improves the CLBR of single oocyte collection in PCOS patients, and is the recommended scheme for IVF treatment in PCOS patients.…”