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Treatment options

Details the treatment options available tocouples with unexplained infertility.

Unexplained infertility

In the absence of a definitive diagnosis, the treatment of unexplained subfertility remains empirical. Treatment options include one of the followings: the wait and see approach, intrauterine insemination, GIFT, IVF and ZIFT.

Expectant management (The wait and see approach)

Without treatment about 50% of the infertile couples will conceive within 3 years, this will depend on many factors such as: the women's age, duration of infertility, previous pregnancy, and the couple wishes. Expectant management is a valid option for couple with a favourable prognosis.

Clomiphene treatment

Women with unexplained infertility may have higher pregnancy rates if they take Clomiphene tablets. It works by correcting subtle ovulatory problems and encouraging the development of many follicles. However, offering ovulation stimulation for unexplained infertility was not advocated by NICE in the UK (2013).

Intrauterine insemination (IUI) with or without mild ovarian stimulation

IUI overcomes hostile cervical factors and ensures close proximity of sperm and egg. Cochrane review in 2012 demonstrated that IUI with ovarian stimulation increases the live-birth rate more than two-folds compared to natural cycle IUI. This should be balanced against the risk of ovarian hyperstimulation and multiple pregnancy. Intrauterine insemination is considered the first line treatment in sub fertile couples with unexplained infertility (The INeS Study Group BMJ 2015). It may be as effective as IVF, less invasive, and less costly. Moreover, IUI is option for patients who have social, cultural or religious objections to IVF. Success rates per IUI treatment cycle is about 10-20%, with 80% of pregnancies occuring within the first four treatment cycles.



IVF treatment with live birth rates between 15-40% is widely accepted treatment for unexplained infertility for couple tried to conceive for a total of 2 years. IVF bypasses unknown potential fertility problems. For older women, couple with a long duration of subfertility, reduced ovarian reserve, IVF should be the primary treatment option.

IVF is preferred to GIFT because it provides information about fertilization. In addition, it avoids laparoscopy with its associated risks and may be performed under a local anesthetic and thus avoiding a general anaesthetic.


Between 5-25 percent of cases of unexplained infertility, no fertilization has been reported with IVF, this is possibly due occult abnormalities in the sperm or eggs. Studies demonstrated higher fertilization in ICSI compared to IVF but failed to show any benefit of ICSI over IVF. Both NICE and American Society do not recommend routine ICSI for unexplained infertility. Some specialists recommend spliting eggs for IVF and ICSI to reduce the risk of failure of fertilization and identify couples who would benefit from ICSI in subsequent treatment.


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