Assessment of Fertility Outcomes Following Combined Clomiphene and Letrozole Versus Letrozole Therapy for the Treatment of Polycystic Ovarian Syndrome Subfertility

Abstract

Background: Poly Cystic Ovarian Syndrome (PCOS) affects 8-13% of women in their reproductive age and is one of the foremost causes of female subfertility. Traditionally, clomiphene citrate has been the first-line treatment for ovulation induction in PCOS. However, the European Society of Human Reproduction and Embryology (ESHRE) international evidence-based guidelines in 2018 recommended the use of letrozole as first-line therapy for ovulation induction in anovulatory PCOS women, due to better pregnancy and live birth rates. Here we aimed to evaluate the effect of combined - clomiphene and letrozole versus letrozole for the treatment of PCOS subfertility. Methods: It was a retrospective cohort study conducted on reproductive-age women fulfilling Rotterdam Criteria for PCOS with a history of subfertility. All participants receiving at least one cycle of letrozole and clomiphene combination were recruited as cases. However, women receiving letrozole only for ovulation induction were taken as controls. Hospital records were abstracted for data on baseline characteristics such as age, duration of infertility, PCOS phenotype, body mass index (BMI), past medical and fertility history, treatment with ovulation induction agents, and metformin use. The mean size of the largest follicle, number of dominant follicles of size greater than 15 mm and endometrial thickness on Days 12-14 or on the day of the luteinizing hormone (LH) surge were recorded. A cycle was termed ovulatory if serum progesterone levels were > 5.0 ng/ml on the seventh day after the LH surge or day 22 in the absence of the LH surge. Data pertaining to therapy-associated side effects were also abstracted from the clinical records. Results: Amongst the ovulatory cycles in both groups, there was no significant difference in the day of the LH surge. Serum progesterone levels on the seventh day post-ovulation were higher with combination therapy (19.35 v/s 26.71, p=0.004). The number of ovulatory cycles was also greater with combination therapy, but the difference was just short of significant (25 vs 18, p=0.08). The mean diameter of the largest follicle, incidence of multi-follicular ovulation, and thin endometrium were similar in both groups. The adverse effect profile was similar in both groups. Conclusion: Combination treatment of clomiphene citrate with letrozole may potentially improve fertility outcomes in PCOS subfertility in terms of the likelihood of ovulation and higher post-ovulatory progesterone levels, however, larger studies are required.

The effect of Bushenhuoxue nutritional decoction in the treatment of overweight patients with polycystic ovarian syndrome

“…By adjusting the patient's diet and developing personalized nutritional interventions, clinicians may, therefore, help patients to reduce weight while minimizing adverse reactions caused by the medication. 17,19 The results of our study showed that glucose metabolism indicators of patients in both groups after the treatment were lower than before the treatment, and significantly lower in patients who received TCM dietary support compared to the control group. This indicates that TCM nutritional therapy can significantly improve the glucose metabolism level of overweight PCOS patients.…”

“… 16 Body weight reduction was reported to restore physical health and reproductive function of PCOS patients. 15 , 17 For instance, Zhang et al 18 showed that weight loss of 6% -7% can restore normal ovulation in some PCOS patients. These studies further strengthening the notion that timely metformin treatment may be beneficial in overweight PCOS patients.…”

“…By adjusting the patient’s diet and developing personalized nutritional interventions, clinicians may, therefore, help patients to reduce weight while minimizing adverse reactions caused by the medication. 17 , 19 …”