Badawy, A., State, O., & Abdelgawad, S. (2007). N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial. Acta Obstetricia Et Gynecologica Scandinavica, 86(2), 218-222. https://doi.org/10.1080/00016340601090337
Badawy A, State O, Abdelgawad S. N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial. Acta Obstet Gynecol Scand. 2007;86(2):218-222. doi:10.1080/00016340601090337
Badawy, Ahmed, et al. "N-Acetyl cysteine and clomiphene citrate for induction of ovulation in polycystic ovary syndrome: a cross-over trial." Acta Obstetricia Et Gynecologica Scandinavica, vol. 86, no. 2, 2007, pp. 218-222.
More women with PCOS ovulated once N-acetyl cysteine joined clomiphene
About 5 out of 10 women ovulated once N-acetyl cysteine joined clomiphene, against about 2 out of 10 on clomiphene alone. This 2007 cross-over trial in Egypt followed 573 women with PCOS. PCOS is also called PMOS (Polyendocrine Metabolic Ovarian Syndrome). Only women who had not ovulated got the combination.
Study at a glance, cross-over trial of 573 women with PCOS: More women with PCOS ovulated once N-acetyl cysteine joined clomiphene. Source: Badawy A et al., 2007, PMID 17364286.
Key Findings
Ovulation occurred in 103 of 573 women (17.9%) on clomiphene citrate alone and 245 of 470 women (52.1%) on clomiphene citrate plus N-acetyl cysteine. The authors report the difference as significant.
Insulin resistance was present in 260 women (55.4%). Ovulation occurred in 129 women with insulin resistance and 116 without, with no significant difference.
Pregnancy occurred in 54 women (11.5%) in the combination cycle: 30 (11.5%) with insulin resistance and 24 (11.4%) without. The authors report no significant difference in pregnancy between those groups.
The authors report significantly higher estrogen, progesterone and endometrial thickness in the combination cycle, and no significant difference in the number of mature follicles.
The paper reports no drug allergy and no ovarian hyperstimulation syndrome. Among the pregnancies were 7 twin pregnancies (12.9%) and 6 first-trimester miscarriages (11.1%).
Interpretation
A cross-over trial gives each participant both treatments in turn. Here each woman received clomiphene alone first, and the 470 who did not ovulate received the combination two months later. The paper describes no placebo, blinding or random assignment. The second group had already failed to ovulate on clomiphene alone, and the two groups overlap. Each treatment lasted one cycle. The women had open tubes and partners with normal semen analysis, so the trial did not include couples with tubal or male-factor infertility. The authors conclude that N-acetyl cysteine is effective and recommend it as an adjuvant.
RRM Context
Ovulation is the central event of the cycle. The trial confirmed it with a mid-luteal blood progesterone test, which marks an ovulatory event. Restorative reproductive medicine asks why ovulation stopped in each woman, including the role of insulin resistance, and follows the cycle with charting. The trial screened prolactin, thyroid-stimulating hormone and 17-OH progesterone and measured insulin resistance in every woman. It then gave one drug regimen to all and did not tailor care to those findings.
Our editorial summary of this paper, not the article's abstract.
Abstract
Objective
To compare clomiphene citrate plus N-acetyl cysteine versus clomiphene citrate for inducing ovulation in patients with polycystic ovary syndrome.
Design
Prospective cross-over trial.
Setting
University teaching hospital and a private practice setting.
Patients
Five hundred and seventy-three patients were treated with clomiphene citrate for one menstrual cycle among which 470 patients were treated with clomiphene citrate plus N-acetyl cysteine for another cycle. All women suffered from polycystic ovary syndrome.
Interventions
Patients had clomiphene citrate 50-mg tablets twice daily alone or with N-acetyl cysteine 1,200 mg/day orally for 5 days starting on day 3 of the menstrual cycle.
Outcome Measures
Primary outcomes were number of mature follicles, serum E2, serum progesterone, and endometrial thickness. Secondary outcome was the occurrence of pregnancy.
Results
Ovulation rate improved significantly after the addition of N-acetyl cysteine (17.9% versus 52.1%). Although the number of mature follicles was more in the N-acetyl cysteine group (2.1+/-0.88 versus 3.2+/-0.93), the difference was not statistically significant. The mean E2 levels (pg/ml) at the time of human chorionic gonadotropine injection, serum progesterone levels (ng/ml) on days 21-23 of the cycle, and the endometrial thickness were significantly improved in the N-acetyl cysteine group. The overall pregnancy rate was 11.5% in the N-acetyl cysteine group. Insulin resistance occurred in 260 patients (55.4%). There was no significant difference between the insulin resistance group (n = 260) and non-insulin resistance group (n = 210) as regards ovulation rate, number of follicles, serum E2 (pg/ml), serum progesterone (ng/ml), endometrial thickness (mm), or pregnancy rate.
Conclusion
N-Acetyl cysteine is proved effective in inducing or augmenting ovulation in polycystic ovary patients.
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