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Unexplained Infertility - Intervention Brings Success July 2002 Welcome In up to 30% of infertile couples, no cause can be immediately identified. This case supports the view that intervention improves conception rates. Assisted reproduction may provide additional diagnostic information. Initial Presentation Elizabeth and Michael S have been partners for 5 years and have used no contraception for thirteen months. Elizabeth is 32 years of age and has always had regular periods approximately thirty days apart with slight dysmenorrhoea on the first day of her periods. Ovulation has been confirmed and intercourse has been appropriately timed around day 12 to day 19 of the cycle. Michael has had type 1 diabetes for 6 years. He is a non-smoker and non-drinker, but Elizabeth smokes 15 cigarettes a day and drinks socially at weekends. Examination of both partners is entirely normal. Consultant Comment Initial review of the history and examination do not suggest any particular problem causing infertility, but a problem with semen quality would be the most likely. A properly timed and collected specimen is required to investigate this (see August 2000 case). It is debatable whether laparoscopy is indicated to exclude fallopian tube occlusions or endometriosis. In the absence of any history or physical findings, the positive yield of laparoscopy is low. Nonetheless, endometriosis may be asymptomatic and its treatment does increase fertility (see November 2000 case). Lifestyle issues need to be addressed. Both Elizabeth and Michael are of normal weight and Elizabeth's normal cycles do not suggest a weight or exercise-related ovulatory disorder. However, recent weight loss of a vigorous exercise program can cause subtle impairment of the luteal phase which can impair fertility. A number of studies have indicated that cigarette smoking in either partner delays conception. In one study, the odds ratio (COR) for delay in conception in women smokers was 1.5 (95% confidence limits 1.3 to 1.8) and in men 1.3 (1.2 to 1.4). Cigarette smokers take one third longer to conceive than non-smokers (Figure 1 below). Elizabeth should be advised accordingly.
Figure 1 - Smokers vs. Non-Smokers Subsequent Progress Michael's semen analysis proves to be entirely normal and Elizabeth elects to have a laparoscopy which is also normal. A search of the Cochrane Database reveals that there is no additional benefit of adding multivitamins to Elizabeth's oral folate in reducing neural tube defects (Lumley K et al 2002). Elizabeth begins a concerted effort to quite smoking. After a further six months, Elizabeth and Michael decide that some other intervention is required. Consultant Comments Unexplained infertility is defined as occurring after eighteen months when no abnormality is diagnosable. Possible explanations might include subtle abnormalities in sperm or tubal function resulting in poor transport of sperm to the fallopian tube, or inability of sperm to fertilise the oocyte. Other possible abnormalities are abnormal embryo development because of poor oocyte quality, or aberrations in endometrial physiology impairing implantation. Without further treatment Michael and Elizabeth have approximately a 30% chance of spontaneous conception over the next two years (Table 1 below). Table 1: Cumulative chance of conception from diagnosis of unexplained infertility
Table 2: Adjustment for positive prognostic factors
Treatment options which have been shown to double this rate in randomised controlled trials include: empirical clomiphene treatment (COR 2.37 with 95% confidence interval of 1.22-4.62) intrauterine insemination with ovulation induction which is more effective than IUI with timed intercourse (COR 2.37 with 95% confidence interval of 1.43-3.90) assisted reproduction with IVF which increases pregnancy rate compared to ovulation induction alone after two cycles of treatment (from 15% to 25%). Conclusion Michael and Elizabeth choose to have FSH stimulation with IUI, but after three cycles they proceed to have IVF. During their first cycle of treatment, it is recognised that more than the usual number of embryos fail to develop normally beyond the 4 cell stage, suggesting an intrinsic oocyte abnormality. However, a pregnancy is achieved with a transfer of one eight cell embryo. Elizabeth remains a non-smoker. IVF was ultimately the definitive diagnostic test for their infertility. References 1. Lumley J et al. Periconceptional supplementation with folate and/or multivitamins for preventing neural tube defects. Cochrane Database of Systemic Reviews 2, 2002. 2. Hughes E et al. Clomiphene Citrate for unexplained subfertility in women. Cochrane Database of Systemic Reviews 2, 2002. 3. Pandian Z et al. Invitro fertilisation for unexplained infertility. Cochrane Database of Systemic Reviews 2, 2002.4. 4. Hughes EG. The effectiveness of ovulation induction and intrauterine insemination in the treatment of persistent infertility: a meta-analysis. Human Reproduction 1997; 12: 1865.  PRINT THIS PAGE
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