Treatments for male subfertility

Review question

Cochrane authors reviewed the evidence about the effectiveness of different treatments for couples with male subfertility.

Background

Intra-uterine insemination (IUI), in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) are frequently-used fertility treatments for couples with low male fertility (subfertility). In IUI, the man's sperm is prepared and placed in the womb (uterus). Thus, the sperm is close to the place where the embryo is made (conception site). IUI can be performed with or without ovarian hyperstimulation (OH). In an OH cycle, women receive drugs to stimulate the ovaries (the organs that produce the eggs (called oocytes)) to increase the number of available oocytes. The main side effects of these drugs are multiple pregnancy (production of two or more embryos (early stage in the development of a baby)) and ovarian hyperstimulation syndrome (OHSS; the ovaries produce too many eggs). In IVF and ICSI, the fertilisation (where the egg and sperm are together and produce an embryo) is outside the body. The oocytes are retrieved from the woman using an ultrasound-guided needle, piercing the vaginal wall to reach the ovaries. Through this needle, follicular fluid, which contains the oocyte, can be aspirated. It is common to remove between 10 and 15 oocytes. In IVF, the eggs are mixed with the sperm in a culture dish. In ICSI, sperm are injected directly into the oocytes to cause fertilisation. The fertilised oocytes are treated for two to six days in a medium that contains nutrients and are then placed in the uterus.

Study characteristics

We searched medical databases for randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) investigating male subfertility. We found 10 randomised controlled trials, all comparing different treatments for couples with male subfertility, with a total of 757 couples. The studies evaluated the following treatment options: timed intercourse (TI; where sex occurred at a recommended time in the menstrual cycle) (with or without OH), IUI (with or without OH), IVF and ICSI. The evidence was current to April 2015. We were mainly interested in how many women had live births and OHSS.

Key results

We found no evidence of a difference in live birth or pregnancy rates between treatments. We also found no evidence of a difference between any of the groups in rates of adverse effects (multiple pregnancy, miscarriage). Available data on OHSS was too limited for us to draw any conclusions.

Quality of the evidence

Most of the evidence was of low or very low quality. The main limitations were failure to describe study methods, small sample sizes and inconsistency in how trials were conducted. Evidence was available for only six of the 14 comparisons that we evaluated. More research is needed.

Authors' conclusions: 

We found insufficient evidence to determine whether there was any difference in safety and effectiveness between different treatments for male subfertility. More research is needed.

Read the full abstract...
Background: 

Intra-uterine insemination (IUI), in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) are frequently used fertility treatments for couples with male subfertility. The use of these treatments has been subject of discussion. Knowledge on the effectiveness of fertility treatments for male subfertility with different grades of severity is limited. Possibly, couples are exposed to unnecessary or ineffective treatments on a large scale.

Objectives: 

To evaluate the effectiveness and safety of different fertility treatments (expectant management, timed intercourse (TI), IUI, IVF and ICSI) for couples whose subfertility appears to be due to abnormal sperm parameters.

Search strategy: 

We searched for all publications that described randomised controlled trials (RCTs) of the treatment for male subfertility. We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO and the National Research Register from inception to 14 April 2015, and web-based trial registers from January 1985 to April 2015. We applied no language restrictions. We checked all references in the identified trials and background papers and contacted authors to identify relevant published and unpublished data.

Selection criteria: 

We included RCTs comparing different treatment options for male subfertility. These were expectant management, TI (with or without ovarian hyperstimulation (OH)), IUI (with or without OH), IVF and ICSI. We included only couples with abnormal sperm parameters.

Data collection and analysis: 

Two review authors independently selected the studies, extracted data and assessed risk of bias. They resolved disagreements by discussion with the rest of the review authors. We performed statistical analyses in accordance with the guidelines for statistical analysis developed by The Cochrane Collaboration. The quality of the evidence was rated using the GRADE methods. Primary outcomes were live birth and ovarian hyperstimulation syndrome (OHSS) per couple randomised.

Main results: 

The review included 10 RCTs (757 couples). The quality of the evidence was low or very low for all comparisons. The main limitations in the evidence were failure to describe study methods, serious imprecision and inconsistency.

IUI versus TI (five RCTs)

Two RCTs compared IUI with TI in natural cycles. There were no data on live birth or OHSS. We found no evidence of a difference in pregnancy rates (2 RCTs, 62 couples: odds ratio (OR) 4.57, 95% confidence interval (CI) 0.21 to 102, very low quality evidence; there were no events in one of the studies).

Three RCTs compared IUI with TI both in cycles with OH. We found no evidence of a difference in live birth rates (1 RCT, 81 couples: OR 0.89, 95% CI 0.30 to 2.59; low quality evidence) or pregnancy rates (3 RCTs, 202 couples: OR 1.51, 95% CI 0.74 to 3.07; I2 = 11%, very low quality evidence). One RCT reported data on OHSS. None of the 62 women had OHSS.

One RCT compared IUI in cycles with OH with TI in natural cycles. We found no evidence of a difference in live birth rates (1 RCT, 44 couples: OR 3.14, 95% CI 0.12 to 81.35; very low quality evidence). Data on OHSS were not available.

IUI in cycles with OH versus IUI in natural cycles (five RCTs)

We found no evidence of a difference in live birth rates (3 RCTs, 346 couples: OR 1.34, 95% CI 0.77 to 2.33; I2 = 0%, very low quality evidence) and pregnancy rates (4 RCTs, 399 couples: OR 1.68, 95% CI 1.00 to 2.82; I2 = 0%, very low quality evidence). There were no data on OHSS.

IVF versus IUI in natural cycles or cycles with OH (two RCTs)

We found no evidence of a difference in live birth rates between IVF versus IUI in natural cycles (1 RCT, 53 couples: OR 0.77, 95% CI 0.25 to 2.35; low quality evidence) or IVF versus IUI in cycles with OH (2 RCTs, 86 couples: OR 1.03, 95% CI 0.43 to 2.45; I2 = 0%, very low quality evidence). One RCT reported data on OHSS. None of the women had OHSS.

Overall, we found no evidence of a difference between any of the groups in rates of live birth, pregnancy or adverse events (multiple pregnancy, miscarriage). However, most of the evidence was very low quality.

There were no studies on IUI in natural cycles versus TI in stimulated cycles, IVF versus TI, ICSI versus TI, ICSI versus IUI (with OH) or ICSI versus IVF.

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