Comparison of Pregnancy Rate in Patients With Polycystic Ovary Syndrome Treated With Clomiphene Alone and in Combination With N-acetyl Cysteine: A Randomized Clinical Trial

Abstract

Objectives: Polycystic ovary syndrome (PCOS) is one of the frequent endocrine disorders among young females, which can cause infertility. Recently, evidence has shown the beneficial impacts of N-acetyl cysteine (NAC) use along with clomiphene citrate on the treatment of infertility caused by PCOS. Regarding this, the present study aimed to compare the pregnancy rate between the PCOS patients treated with clomiphene and those received clomiphene along with NAC. Materials and Methods: This blinded randomized controlled clinical trial was performed on 66 patients with PCOS who presented with infertility at Milad Infertility Center in Mashhad, Iran, in 2015. The patients were divided into two groups of intervention and control using a random number table. In the intervention group, 100 mg of clomiphene (i.e. two pills) along with 1200 mg of NAC (i.e. two 600 mg pills) were given to the participants from the third day of the menstrual cycle for five days. In the control group, 100 mg of clomiphene was administered from the third day of the cycle for 5 days. The patients’ response to medications as well as the number and size of follicles were assessed using the vaginal ultrasound. Results: The 2 study groups had no significant difference regarding age, duration of infertility, body mass index, history of infertility treatment, and endometrial thickness on the third day of the menstrual cycle. The mean endometrial thickness was 7.47±1.6 (NAC/ clomiphene) and 7.58±2.1 mm (clomiphene) on the 12th day of the menstrual cycle (P=0.810). Furthermore, the mean sizes of the follicles were 13.6±4.2 (clomiphene) and 15.9±5.1 mm (NAC/clomiphene) (P=0.301). The mean numbers of follicles were 1.56±0.9 (clomiphene) and 1.8±0.9 (NAC/clomiphene) (P=0.069). In total, 7 (21.2%) and 5 (15.1%) patients in the intervention and control groups had a positive beta-hCG result, respectively (P=0.260). Conclusions: As the findings of this study revealed, the addition of NAC to clomiphene treatment was not associated with an increased chance of pregnancy in patients with PCOS-related infertility.

The effect of clomiphene citrate, herbal mixture, and herbal mixture along with clomiphene citrate on clinical and para-clinical parameters in infertile women with polycystic ovary syndrome: a randomized controlled clinical trial

“…CC as a selective estrogen-receptor modulator, increases pituitary gonadotropin (i.e., FSH and LH) release, promotes ovulation, and improves menstrual cycles by exerting negative feedback on the hypothalamus [13]. However, it may be associated with a number of side effects including the reduction in the endometrial thickness [14], nausea, vomiting, hot flashes, higher multiple pregnancy, breast discomfort, and ovarian hyperstimulation syndrome [13].…”

The effects of N-acetylcysteine on ovulation and sex hormones profile in women with polycystic ovary syndrome: a systematic review and meta-analysis

“…Overall, five studies were defined as high quality (18,20,24,26,5) . In the study by Gayatri et al (28) , participants were not randomly assigned to the intervention and control groups, and seven studies described an allocation concealment method (18,(20)(21)(22)23,5,8) . The blinding of subjects and researchers was reported in four studies (22,9,27,28) .…”

“…Thus ovaries may store numerous immature follicles and fail to release an egg regularly (4) . N-acetyl cysteine (NAC) is a safe, economic, and affordable drug which is used for the stimulation of ovulation (5) . This medication is an acetylated variant of L-cysteine, a great source of sulfhydryl groups.…”

“…Results of a recent study showed no effect of NAC on levels of FSH, LH and FSH/LH ratio among infertile PCOS women (12) . In another study, NAC supplementation had no significant effect on serum levels of sex hormone-binding globulin (SHBG), LH, FSH, LH/FSH, E2 and testosterone in PCOS patients after 12 weeks (5,9,12,13) .…”

“…Indeed the role of NAC on sexual hormones is characterised as decreased serum levels of testosterone and androgen levels among PCOS women, reduced levels of FSH and LH and increased levels of testosterone in infertile men (5) . Also, serum levels of oestradiol (E2) and progesterone were improved in PCOS women after NAC consumption (9) .…”