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Gonadotropins succeed where clomifene fails

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Infertile couples may be motivated to try more medication

The study findings will be useful to clinicians in practice because infertile couples often balk at the idea of trying another several months of medication rather than trying in vitro fertilization (IVF) after 6 months of failed medical treatment, wrote Cynthia Farquhar, MD, in an accompanying editorial (Lancet. 2017 Dec 19. doi: 10.1016/S0140-6736[17]33310-X).

Data from previous studies have shown that ovarian induction and intrauterine insemination are as successful as IVF treatments, but many couples feel time pressured and want to move to IVF earlier, and data to support the success of medical treatments after 6 months have been lacking, she said.

Although intrauterine insemination had no additional effect on the live birth rates, the study results for both clomifene citrate and gonadotropins suggest that fertility clinics should offer ovulation induction for 12 months using either clomifene citrate or gonadotropins, according to cost and convenience, she said.

“If there is one thing to take away from this study, it is to offer up to 12 cycles of ovulation induction in women with normogonadotropic anovulation before offering assisted reproductive technology,” Dr. Farquhar noted.

Dr. Farquhar is affiliated with the department of obstetrics and gynaecology and the faculty of medical and health sciences at the University of Auckland, New Zealand. She had no financial conflicts to disclose.



Switching to gonadotropins increased the odds of live births for women with normogonadotropic anovulation with little success for continuing with clomifene citrate, based on data from 666 women.

Women who have not become pregnant after six cycles of clomifene are often defined as having failed the treatment, but the effectiveness of continuing clomifene citrate or switching to gonadotropins had not been addressed in randomized trials, wrote Nienke S. Weiss, MD, of VU University Medical Center, Amsterdam, and her colleagues.

In a study published online in the Lancet, the researchers randomized 166 women to gonadotropins and intrauterine insemination, 165 to gonadotropins and intercourse, 163 to clomifene citrate and intrauterine insemination, and 172 to clomifene citrate and intercourse. The study population included women aged 18 years and older who had not become pregnant after six cycles of clomifene citrate. The clomifene citrate was given as oral doses of 50-150 mg daily, and gonadotropin was given subcutaneously at a starting dose of 50 IU or 75 IU daily.

Overall, live births were significantly more likely for women given gonadotropins, compared with those given clomifene citrate (52% of 327 women vs. 41% of 334 women, respectively; P = .0124). Rates of multiple pregnancies were similar and relatively low among the treatment groups.

Intrauterine insemination had no significant impact on live birth rates, compared with intercourse (49% vs. 43%, respectively; P = .1152).

A total of three adverse events were reported including one stillbirth and one case of congenital abnormality in the clomifene group and one delivery at 20 weeks’ gestational age caused by cervical insufficiency in the gonadotropin group. More miscarriages were reported in the gonadotropin group than in the clomifene group, but the study was not powered to address this difference, which should be addressed in future studies, the researchers said.

The findings were limited by each center’s use of its own ovulation induction protocols, the researchers noted. “Our results can be used by couples treated with first-line ovulatory drugs who weigh the pros and cons of switching to gonadotropins and addition of intrauterine insemination,” they said.

The study was supported by the Netherlands Organization for Health Research and Development.

SOURCE: Weiss N et al. Lancet. 2017 Dec 19. doi: 10.1016/S0140-6736(17)33308-1.

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