Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial

Bhattacharya S; Harrild K; Mollison J; Wordsworth S; Tay C; Harrold A; McQueen D; Lyall H; Johnston L; Burrage J; Grossett S; Walton H; Lynch J; Johnstone A; Kini S; Raja A; Templeton A

doi:10.1136/bmj.a716

Assisted Reproduction Outcomes and Effectiveness

Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial

Bhattacharya S, Harrild K, Mollison J, Wordsworth S, Tay C, Harrold A, McQueen D, Lyall H, Johnston L, Burrage J, Grossett S, Walton H, Lynch J, Johnstone A, Kini S, Raja A, Templeton A

Published August 7, 2008 BMJ (Clinical research ed.)

DOI 10.1136/bmj.a716 PMID 18687718 PMC PMC2505091

RRM Academy Synopsis

Clomiphene and insemination did not clearly raise live births

In a Scottish randomized trial of 580 couples with unexplained infertility followed for six months, neither clomiphene nor insemination clearly raised live births above waiting. About 17 out of 100 waiting couples had a baby. The figures were 14 out of 100 on clomiphene and 23 out of 100 on insemination.

Key Findings

Live births occurred in 32/193 (17%) with expectant management, 26/192 (14%) with clomiphene citrate, and 43/191 (23%) with unstimulated intrauterine insemination.
Odds of a live birth, relative to expectant management: 0.79 (95% confidence interval 0.45 to 1.38) for clomiphene citrate and 1.46 (0.88 to 2.43) for insemination.
Three women (2%) in the clomiphene group and 14 (7%) in the insemination group became pregnant spontaneously and had a live birth.
The process of treatment was acceptable to 159/170 (94%) on clomiphene and 155/162 (96%) on insemination, against 123/153 (80%) with expectant management.
Abdominal pain affected 40/169 (24%) on clomiphene against 5/159 (3%) with expectant management. Headache affected 33/167 (20%) against 6/159 (4%).

Interpretation

The trial was pragmatic and randomized, with an untreated comparison group. Couples had at least two years of infertility, confirmed ovulation, open tubes, and normal semen. Five Scottish centers recruited them. Fewer than 20% of couples assigned to insemination finished six cycles in the six-month window. The authors cannot exclude a higher live birth rate with more cycles. The insemination interval runs from slightly below waiting to well above it. Clomiphene combined with insemination was outside the trial.

RRM Context

Unexplained infertility means standard tests found no cause. RRM calls it undiagnosed, and both active arms treated couples before any cause was found. The trial recommended no charting measures to the waiting arm, such as basal temperature charts or luteinizing hormone kits. RRM looks for the cause in both partners.

Our editorial summary of this paper, not the article's abstract.

Abstract

Objective

To compare the effectiveness of clomifene citrate and unstimulated intrauterine insemination with expectant management for the treatment of unexplained infertility.

Design

Three arm parallel group, pragmatic randomised controlled trial.

Setting

Four teaching hospitals and a district general hospital in Scotland.

Participants

Couples with infertility for over two years, confirmed ovulation, patent fallopian tubes, and motile sperm.

Intervention

Expectant management, oral clomifene citrate, and unstimulated intrauterine insemination.

Main Outcome Measures

The primary outcome was live birth. Secondary outcome measures included clinical pregnancy, multiple pregnancy, miscarriage, and acceptability.

Results

580 women were randomised to expectant management (n=193), oral clomifene citrate (n=194), or unstimulated intrauterine insemination (n=193) for six months. The three randomised groups were comparable in terms of age, body mass index, duration of infertility, sperm concentration, and motility. Live birth rates were 32/193 (17%), 26/192 (14%), and 43/191 (23%), respectively. Compared with expectant management, the odds ratio for a live birth was 0.79 (95% confidence interval 0.45 to 1.38) after clomifene citrate and 1.46 (0.88 to 2.43) after unstimulated intrauterine insemination. More women randomised to clomifene citrate (159/170, 94%) and unstimulated intrauterine insemination (155/162, 96%) found the process of treatment acceptable than those randomised to expectant management (123/153, 80%) (P=0.001 and P<0.001, respectively).

Conclusion

In couples with unexplained infertility existing treatments such as empirical clomifene and unstimulated intrauterine insemination are unlikely to offer superior live birth rates compared with expectant management.

Trial Registration

ISRCT No: 71762042.

Topics

Assisted Reproduction › Outcomes and Effectiveness › Live Birth Rates · Therapeutics › Ovulation Agents › Selective Estrogen Receptor Modulators

PMID 18687718 18687718 DOI 10.1136/bmj.a716 10.1136/bmj.a716 Bhattacharya et al. 2008, Bhattacharya 2008

Clomifene citrate or unstimulated intrauterine insemination compared with expectant management for unexplained infertility: pragmatic randomised controlled trial

Clomiphene and insemination did not clearly raise live births

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

Predicting the chances of having a baby with or without treatment at different time points in couples with unexplained subfertility

Defining infertility--a systematic review of prevalence studies

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