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Meta-Analysis
. 2014 Dec 21;2014(12):CD006942.
doi: 10.1002/14651858.CD006942.pub3.

Synchronised approach for intrauterine insemination in subfertile couples

Astrid E P Cantineau  1 , Mirjam J Janssen, Ben J Cohlen, Thomas Allersma
Affiliations
Meta-Analysis

Synchronised approach for intrauterine insemination in subfertile couples

Astrid E P Cantineau et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: In many countries intrauterine insemination (IUI) is the treatment of first choice for a subfertile couple when the infertility work up reveals an ovulatory cycle, at least one open Fallopian tube and sufficient spermatozoa. The final goal of this treatment is to achieve a pregnancy and deliver a healthy (singleton) live birth. The probability of conceiving with IUI depends on various factors including age of the couple, type of subfertility, ovarian stimulation and the timing of insemination. IUI should logically be performed around the moment of ovulation. Since spermatozoa and oocytes have only limited survival time correct timing of the insemination is essential. As it is not known which technique of timing for IUI results in the best treatment outcome, we compared different techniques for timing IUI and different time intervals.

Objectives: To evaluate the effectiveness of different synchronisation methods in natural and stimulated cycles for IUI in subfertile couples.

Search methods: We searched for all publications which described randomised controlled trials of the timing of IUI. We searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (1966 to October 2014), EMBASE (1974 to October 2014), MEDLINE (1966 to October 2014) and PsycINFO (inception to October 2014) electronic databases and prospective trial registers. Furthermore, we checked the reference lists of all obtained studies and performed a handsearch of conference abstracts.

Selection criteria: Randomised controlled trials (RCTs) comparing different timing methods for IUI were included. The following interventions were evaluated: detection of luteinising hormone (LH) in urine or blood, single test; human chorionic gonadotropin (hCG) administration; combination of LH detection and hCG administration; basal body temperature chart; ultrasound detection of ovulation; gonadotropin-releasing hormone (GnRH) agonist administration; or other timing methods.

Data collection and analysis: Two review authors independently selected the trials, extracted the data and assessed study risk of bias. We performed statistical analyses in accordance with the guidelines for statistical analysis developed by The Cochrane Collaboration. The overall quality of the evidence was assessed using GRADE methods.

Main results: Eighteen RCTs were included in the review, of which 14 were included in the meta-analyses (in total 2279 couples). The evidence was current to October 2013. The quality of the evidence was low or very low for most comparisons . The main limitations in the evidence were failure to describe study methods, serious imprecision and attrition bias.Ten RCTs compared different methods of timing for IUI. We found no evidence of a difference in live birth rates between hCG injection versus LH surge (odds ratio (OR) 1.0, 95% confidence interval (CI) 0.06 to 18, 1 RCT, 24 women, very low quality evidence), urinary hCG versus recombinant hCG (OR 1.17, 95% CI 0.68 to 2.03, 1 RCT, 284 women, low quality evidence) or hCG versus GnRH agonist (OR 1.04, 95% CI 0.42 to 2.6, 3 RCTS, 104 women, I(2) = 0%, low quality evidence).Two RCTs compared the optimum time interval from hCG injection to IUI, comparing different time frames that ranged from 24 hours to 48 hours. Only one of these studies reported live birth rates, and found no difference between the groups (OR 0.52, 95% CI 0.27 to 1.00, 1 RCT, 204 couples). One study compared early versus late hCG administration and one study compared different dosages of hCG, but neither reported the primary outcome of live birth.We found no evidence of a difference between any of the groups in rates of pregnancy or adverse events (multiple pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS)). However, most of these data were very low quality.

Authors' conclusions: There is insufficient evidence to determine whether there is any difference in safety and effectiveness between different methods of synchronization of ovulation and insemination. More research is needed.

PubMed Disclaimer

Conflict of interest statement

None known for any of the review authors.

Figures

1
1
Study flow diagram for 2009 to 2013 literature searches.
2
2
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
3
3
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
4
4
Forest plot of comparison: 1 hCG versus LH surge, outcome: 1.2 pregnancy rate per couple.
5
5
Forest plot of comparison: 2 u‐hCG versus r‐hCG, outcome: 2.2 pregnancy rate per couple.
6
6
Forest plot of comparison: 2 u‐hCG versus r‐hCG, outcome: 2.4 miscarriage rate per pregnancy.
7
7
Forest plot of comparison: 3 short versus long interval, outcome: 3.2 pregnancy rate per couple.
8
8
Forest plot of comparison: 3 short versus long interval, outcome: 3.3 miscarriage rate per pregnancy.
9
9
Forest plot of comparison: 4 hCG versus GnRH‐a, outcome: 4.1 live birth rate per couple.
10
10
Forest plot of comparison: 4 hCG versus GnRH‐a, outcome: 4.2 pregnancy rate per couple.
11
11
Forest plot of comparison: 4 hCG versus GnRH‐a, outcome: 4.3 multiple pregnancy rate per pregnancy.
12
12
Forest plot of comparison: 4 hCG versus GnRH‐a, outcome: 4.4 miscarriage rate per pregnancy.
1.1
1.1. Analysis
Comparison 1 hCG versus LH surge, Outcome 1 live birth rate per couple.
1.2
1.2. Analysis
Comparison 1 hCG versus LH surge, Outcome 2 pregnancy rate per couple.
1.3
1.3. Analysis
Comparison 1 hCG versus LH surge, Outcome 3 multiple pregnancy rate per pregnancy.
2.1
2.1. Analysis
Comparison 2 u‐hCG versus r‐hCG, Outcome 1 live birth rate per couple.
2.2
2.2. Analysis
Comparison 2 u‐hCG versus r‐hCG, Outcome 2 pregnancy rate per couple.
2.3
2.3. Analysis
Comparison 2 u‐hCG versus r‐hCG, Outcome 3 multiple pregnancy rate per pregnancy.
2.4
2.4. Analysis
Comparison 2 u‐hCG versus r‐hCG, Outcome 4 miscarriage rate per pregnancy.
2.5
2.5. Analysis
Comparison 2 u‐hCG versus r‐hCG, Outcome 5 OHSS rate per cycle.
3.1
3.1. Analysis
Comparison 3 Short versus long interval, Outcome 1 live birth rate per couple.
3.2
3.2. Analysis
Comparison 3 Short versus long interval, Outcome 2 pregnancy rate per couple.
3.3
3.3. Analysis
Comparison 3 Short versus long interval, Outcome 3 miscarriage rate per pregnancy.
4.1
4.1. Analysis
Comparison 4 hCG versus GnRH‐a, Outcome 1 live birth rate per couple.
4.2
4.2. Analysis
Comparison 4 hCG versus GnRH‐a, Outcome 2 pregnancy rate per couple.
4.3
4.3. Analysis
Comparison 4 hCG versus GnRH‐a, Outcome 3 multiple pregnancy rate per pregnancy.
4.4
4.4. Analysis
Comparison 4 hCG versus GnRH‐a, Outcome 4 miscarriage rate per pregnancy.
4.5
4.5. Analysis
Comparison 4 hCG versus GnRH‐a, Outcome 5 OHSS per cycle.
5.1
5.1. Analysis
Comparison 5 Early hCG versus late hCG, Outcome 1 pregnancy rate per couple.
5.2
5.2. Analysis
Comparison 5 Early hCG versus late hCG, Outcome 2 miscarriage rate.
6.1
6.1. Analysis
Comparison 6 Different dosages of hCG, Outcome 1 pregnancy rate per couple.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

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Wang 2001 {published data only}
    1. Wang C, Horng S, Chang C, Huang H, Wang H, Soong Y. Delayed HCG injection and earlier insemination can improve the outcome of IUI ‐ a novel and simplified protocol. 17th World Congress on Fertility and Sterility 2001;Abstract book:189.
Wang 2006 {published data only}
    1. Wang CW, Horng SG, Chen CK, Wang HS, Huang HY, Soong YK. Delayed timing of human chorionic gonadotropin injection in combination with earlier insemination can improve the outcome of intrauterine insemination. Human Reproduction 2006;21 Suppl:i119.

References to studies awaiting assessment

Aydin 2013 {published data only}
    1. Aydin Y, Hassa H, Oge T, Tokgoz Y. A randomized study of simultaneous hCG administration with intrauterine insemination in stimulated cycles. European Journal of Obstetrics & Gynecology and Reproductive Biology 2013;170:444‐8. - PubMed
Blockeel 2014 {unpublished data only}
    1. Blockeel C, Knez J, Polyzos NP, Vos M, Camus M, Tournaye H. Should an intrauterine insemination with donor semen be performed 1 or 2 days after the spontaneous LH rise? A prospective RCT. Human Reproduction 2014;29(4):697‐703. - PubMed
    1. Blockeel C, Polyzos N, Ermini B, Riva A, Stoop D, Tournaye H, Devroey P. Timing of IUI 24 or 48 hours after spontaneous LH peak. ClinicalTrials.gov June 29, 2012.
Dehghani 2014 {published data only}
    1. Dehghani‐Firouzabai R, Aflatoonian A, Davar R, Farid‐Mojtahedi M. A comparison of pregnancy rate before and after the administration of HCG in intrauterine insemination. Archives of Gynecology and Obstetrics 2014;29(2):429‐32. - PubMed
Mostafa 2014 {published data only}
    1. Mostafa MS, Huseiny AM, Soliman BS, Mohammed MM. Effect of postponing hCG injection after intrauterine insemination on pregnancy rate. Middle East Fertility Society Journal 2014;19(3):183‐6.

References to ongoing studies

OVO R&D 2012 {unpublished data only}
    1. Combining Urinary Luteinizing hormone Testing with ultrasound monitoring in intrauterine insemination cycles. Ongoing study January 2011. - PubMed

Additional references

Andersen 1995
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Cantineau 2007
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Cohlen 1998
    1. Cohlen BJ, Velde ER, Kooij RJ, Looman CW, Habbema JD. Controlled ovarian hyperstimulation and intrauterine insemination for treating male subfertility: a controlled study. Human Reproduction 1998;13(6):1553‐8. - PubMed
Cooper 2010
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Higgins 2011
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Kosmas 2006
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Kruger 1993
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Miller 1996
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Steures 2006
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WHO 1980
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WHO 1987
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WHO 1992
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WHO 2010
    1. World Health Organisation. WHO manual for the examination and processing of human semen. Geneva: World Health Organisation, 2010.

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