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Gonadotrophins for idiopathic male factor subfertility

  1. Abdelhamid M Attia1,*,
  2. Ahmed M Abou-Setta2,
  3. Hesham G Al-Inany1

Editorial Group: Cochrane Menstrual Disorders and Subfertility Group

Published Online: 23 AUG 2013

Assessed as up-to-date: 14 JAN 2013

DOI: 10.1002/14651858.CD005071.pub4


How to Cite

Attia AM, Abou-Setta AM, Al-Inany HG. Gonadotrophins for idiopathic male factor subfertility. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD005071. DOI: 10.1002/14651858.CD005071.pub4.

Author Information

  1. 1

    Faculty of Medicine, Cairo University, Obstetrics & Gynaecology, Cairo, Egypt

  2. 2

    University of Manitoba, Centre for Healthcare Innovation, Winnipeg, Manitoba, Canada

*Abdelhamid M Attia, Obstetrics & Gynaecology, Faculty of Medicine, Cairo University, 18 El-Ghaith St., Cairo, 12311, Egypt. attia2@gmail.com. aattia@thewayout.net.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 23 AUG 2013

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Characteristics of included studies [ordered by study ID]
Baccetti 2004

MethodsCountry of study: Germany

Number of centres: single centre

Consent: reported

Ethical approval: not reported

Timing of trial: not reported

Source of funding: a grant from the Italian Ministry for Universities and Technological Research, 2000

Numbers of participants

  • Recruited: not reported
  • Randomly assigned: 44 couples (treated = 24 groups; non-treated control = 20 groups)
  • Excluded: none reported
  • Lost to follow-up: none reported
  • Analysed: 44


ParticipantsPre-allocation examinations and studies: Andrological and gynaecological examinations for males and their partners. Semen analysis and transmission electron microscopy. Female partners underwent a complete infertility work-up

Inclusion criteria

  • Idiopathic male infertility
  • Normal or low baseline endocrine parameters, including plasma concentrations of FSH, LH, prolactin, 17B-estradiol and testosterone
  • Absence of urinogenital tract infection or inflammation
  • Unremarkable medical history
  • Oligo- and/or asthenozoospermia (WHO 1999)
  • Failure in at least two in vitro fertilization (IVF) or IUI treatment cycles
  • Female partners: No health or fertility problems on gynaecological examination and complete infertility work-up. No untreatable hormonal irregularities


Exclusion criteria

  • Plasma concentrations of FSH > 12 mIU/mL


Age

  • Men: range 28 to 45
  • Women: mean 32


Duration of follow-up: 12 weeks of therapy


InterventionsTreatment group: 150 IU/day s.c.Highly purified FSH (Fertinorm HP, Serono)
Control group: no treatment
Female partners underwent hormonal stimulation with HMG and HCG, sonographic monitoring of follicular growth, oocyte aspiration, ICSI; up to 3 embryos were transferred to the uterine cavity two days after oocyte retrieval
Duration of intervention: 12 weeks
Follow-up examinations: semen analysis by optical microscopy before and after FSH treatment. Sperm count and motility were assessed using a Makler counting chamber. Aliquots of each semen sample were examined by transmission electron microscopy (TEM)


OutcomesPrincipal and secondary: sperm parameters and pregnancy rate
Methods of assessing outcome measures: Clinical pregnancy was determined by ultrasound evidence of a foetal sac 6 weeks after embryo transfer
Adverse events: not reported


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAuthors reported using "true randomisation" with no further details

Allocation concealment (selection bias)Low riskAuthors reported using third party randomisation

Blinding (performance bias and detection bias)
All outcomes
Unclear riskThe authors did not report blinding of participants or outcome assessors. From the study design (treatment vs no treatment), the most probable scenario was an open-label study design

Incomplete outcome data (attrition bias)
All outcomes
Low riskAuthors did not report any dropouts and analysed outcomes using the intention-to-treat principle

Selective reporting (reporting bias)Unclear riskProtocol was not reviewed, but outcomes in the methods and results sections are similar

Other biasUnclear riskBaseline characteristics for both groups reported with no mention of similarity between groups nor of results of any statistical comparison of homogeneity

Foresta 2005

MethodsCountry of study: Italy

Number of centres: single centre

Consent: reported

Ethical approval: reported

Timing of trial: not reported

Source of funding: not reported

Numbers of participants

  • Recruited: not reported
  • Randomly assigned: 128 (65 treatment group and 63 non-treatment group). NB: 40 fertile normozoospermic matched controls were used as controls for hormone and seminal parameters (but were not used in fertility assessment)
  • Excluded: 6 couples (2 among the treatment group and 4 among the non-treatment group) were subsequently excluded from the study because of concurrent illnesses
  • Lost to follow-up: Ten participants (1 among the treatment group and 9 among the non-treatment group) dropped out before completing the study. Two of the non-treatment group were lost, 7 of the non-treatment group dropped out by request and 1 of the treatment group discontinued intervention
  • Analysed: 112 completed the study (62 of the treatment group and 50 of the non-treatment group)


ParticipantsPre-allocation examinations and studies: Exclusion of common conditions such as history of cryptorchidism, post-mumps orchitis, testicular torsion or trauma, varicocele; seminal tract infections, anti-sperm antibodies and Y chromosome microdeletion, karyotypic abnormalities and CFTR gene mutations. Ultrasound scanning of the testis to evaluate testicular size and morphology, followed by testicular aspiration Testicular structure was analysed in all participants by means of bilateral fine-needle aspiration cytology (FNAC). Semen evaluations were performed in a blinded fashion by the same operator. FSH, LH and testosterone plasma concentrations were measured by RIA using standard methods. Inhibin B plasma concentrations were measured by a solid phase sandwich enzyme-linked immunosorbent assay (ELISA) specific for the dimeric inhibin-B

Inclusion criteria

  • History of infertility for at least 2 years
  • Sperm count < 10 million/mL on at least three separate occasions
  • Idiopathic infertility
  • Normal plasma levels of FSH (range 1 to 7 IU/L), LH (range 2 to 6 IU/L), prolactin (range 15 to 25 ng/mL), testosterone (range 3 to 9 ng/mL) and inhibin B (> 150 pg/mL)
  • Female partners have no ovulatory disorders, tubal factor or endocrine abnormalities as evaluated by endocrine evaluation, pelvic ultrasound examination and hysterosalpingography


Exclusion criteria: none stated

Age

  • Men: mean age 34.2 (treatment group) and 34 (control group)
  • Women: mean age 32.3 (treatment group) and 31.8 (control group)


Duration of follow-up: 3 months' treatment, 3 months' follow-up, then re-randomisation and ART trials (3 months)


InterventionsTreatment group: 100 IU r-hFSH IM on alternate days for 3 months

Control group: no treatment

Duration of intervention: 3 months

Follow-up examinations: The study was divided into 3 periods

  • A period of treatment with r-hFSH for 3 months (therapy period). At the end of this period, semen analysis was performed in all participants by the same operator
  • A period of 3 months after withdrawal of therapy, in which all participants were monitored for semen parameters and spontaneous pregnancies (follow-up period). Participants were encouraged to have a special coitus frequency, at least two to three times per week, particularly at midcycle
  • The following 3 month period, in which all participants who had not reached pregnancy during the two previous periods underwent ART. Participants with a total number of motile post-wash spermatozoa > 5 million were randomly enrolled to IUI for 3 cycles or to IVF for 1 cycle, and those with total motile spermatozoa < 5 million were enrolled in only IVF-ET or ICSI (one cycle) according to specific indications. Six months after the withdrawal of r-hFSH therapy, another sperm analysis was performed in all participants


OutcomesPrincipal and secondary: sperm parameters and pregnancy rate
Methods of assessing outcome measures: measuring B-hCG plasma levels
Adverse events: not reported


NotesChanges in trial protocol: after the initial 6-month period (3 months' treatment and 3 months' follow-up) a major change in the initial protocol necessitated exclusion of this period from the analysis in the SR
Contact with author: The study was first sent to us upon personal communication (unpublished data), but later, it was published (September 2005)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskAuthors reported that participants were randomly allocated to treatment or no treatment groups with a random number generator

Allocation concealment (selection bias)Low riskAuthors reported using third party randomisation

Blinding (performance bias and detection bias)
All outcomes
Unclear riskAuthors did not report blinding of participants or outcome assessors, except for semen analysis. From the study design (treatment vs no treatment), the most probable scenario was an open-label study design

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskSixty-five men were allocated to the treatment group and 63 to the no treatment group. Of these, 6 couples (2 from the treatment group and 4 from the non-treatment group) were subsequently excluded from the study because of concurrent illnesses. Ten participants (1 from the treatment group and 9 from the no treatment group) dropped out before completing the study: 2 in the no treatment group were lost, 7 in the no treatment group dropped out by participant request and 1 in the treatment group discontinued intervention. Therefore, 112 men (87.5%) affected by idiopathic oligozoospermia completed the study (62 in the treatment group and 50 in the no treatment group), were analysed and are described

Selective reporting (reporting bias)Unclear riskProtocol was not reviewed, but outcomes in the methods and results sections are similar

Other biasUnclear riskBaseline characteristics for both groups are reported, but no mention is made of similarity between groups. Statistical comparison of homogeneity between baseline characteristics of the groups shows statistically significant differences in sperm concentration and forward motility in the control group

Kamischke 1998

MethodsCountry of study: Germany

Number of centres: single centre

Consent: reported

Ethical approval: reported

Timing of trial: March 1994 to November 1996

Source of funding: supported in part by the Federal Health Ministry (Bonn), the Deutsche Forschungsgemeinschaft (DFG, Bonn) and Ares-Serono (Unterschleissheim, Germany)

Numbers of participants

  • Recruited: 211, but 144 refused or had intercurrent illnesses, varicocele, undescended testis, abnormal hormone values or female causes


Complete physical, hormonal and semen examination. Detailed medical histories of the participant and female partner, physical examination, clinical chemistry, red blood cell count, clotting factors, hormones (luteinizing hormone (LH), FSH, prolactin, testosterone, oestradiol), semen analysis and flow cytometry of sperm DNA. In addition, scrotal content was examined by ultrasonography. at one pre-examination and at cessation of medication. Electron microscopy (EM) was included in the analysis at the second pre-examination and was performed in 31 participants

  • Randomly assigned: 67 (treatment 34 and placebo 33); 66 completed the study, including 3 months' follow-up after the last examination
  • Excluded: 1 (placebo) proved immunological infertility after completion
  • Lost to follow-up: 1 dropout (placebo) before completion (personal reasons)
  • Analysed: 65 (treatment 34 and placebo 31)
  • Of the 65, 4 were excluded from the pregnancy analysis because of later endoscopically confirmed tubal blockage (n = 3) or pregnancy (n = 1) in their partners, 4 days before initiation of medication


ParticipantsPre-allocation examination and studies: At the first screening examination, a complete physical, hormonal and semen examination was performed. If the results of the first screening examination were in accordance with the inclusion criteria, a second pre-examination was performed, including detailed medical histories of the participant and female partner, physical examination, clinical chemistry, red blood cell count, clotting factors, hormones (luteinizing hormone (LH), FSH, prolactin, testosterone, oestradiol), semen analysis and flow cytometry of sperm DNA. In addition, scrotal content was examined by ultrasonography at one pre-examination and at cessation of medication. Electron microscopy (EM) was included in the analysis at the second pre-examination and was performed in 31 participants

Inclusion criteria

  • Age > 18 years
  • Infertility duration > 1 year
  • No acute or history of varicocoele, undescended testis or testicular cancer, drug or alcohol abuse or any major systemic disease
  • No azoospermia and at least two semen parameters (motility, concentration, morphology) below WHO criteria and no signs of genital tract infection or immunological infertility
  • Basal FSH concentrations < 12 IU/L, and other reproductive hormones (LH, prolactin, testosterone, oestradiol) are normal
  • Female partners had normal ovulatory cycles and biphasic basal body temperature


Exclusion criteria

  • Females with untreatable ovarian dysfunction, known endometriosis or tubal blockage


Mean age 32.89 years. Mean BMI 25.63 kg/m2. Mean duration of infertility 4.6 years
Duration of follow-up 24 weeks (12 treatment + 12 follow-up) + 3 months


InterventionsTreatment group: daily SC injections of 150 IU rhFSH (Gonal-F, Serono) with 30 mg saccharose same time of day by participants themselves. Treatment started 1.2 ± 0.2 months after the last pre-examination
Control group: same method but with placebo containing saccharose 30 mg alone
Duration of intervention: 12 weeks
Follow-up examinations: control examinations: 6 and 12 weeks after initiation of treatment and 6 and 12 weeks after cessation of treatment (medical histories of participant and female partner, detection of adverse events and side effects, physical evaluation and clinical chemistry, red blood cell count, clotting factors, hormone analysis (LH, FSH, inhibin B, testosterone, oestradiol), semen analysis and flow cytometry of sperm DNA). In participants for whom EM analysis had been performed at the pre-examination, it was repeated 12 weeks after initiation and 12 weeks after cessation of treatment
An additional ultrasound examination of scrotal content was performed 12 weeks after initiation of treatment
Pregnancies in female partners were recorded a further 3 months after the last control examination


OutcomesPrincipal and secondary. Primary: sperm parameters. Secondary: pregnancy
Methods of assessing outcome measures: US and HCG concentration increase
Adverse events: not reported


NotesExcluded from the analysis by authors: After the 6-month observation period after treatment, further pregnancies of female partners occurred with the aid of ICSI (treated n = 4, placebo n = 7), IVF (treated n = 1) or insemination (placebo n = 1), or spontaneously (treated n = 1)
Contact with the author: contacted twice. At first, author informed us that the spontaneous pregnancy that occurred before treatment was reported in the treatment group. We then asked about the number of participants who underwent ART but received no answer until now


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAuthors reported using "true randomisation" with no further details

Allocation concealment (selection bias)Low riskAuthors reported "third party randomization" and that the code distinguishing the treatment groups was blinded for the examiners

Blinding (performance bias and detection bias)
All outcomes
Low riskAuthors reported that the code distinguishing the treatment groups was blinded for the examiners and that they used a placebo, but explicit description of blinding of participants was not reported and was assumed

Incomplete outcome data (attrition bias)
All outcomes
Low risk67 participants were allocated to treated or placebo groups. One participant (placebo) dropped out for personal reasons before completing the study. Another participant (placebo) was excluded after completing the study because the mixed agglutination reaction (MAR) test at the last three examinations revealed IgG and IgA titres between 50% and 100% as a sign of immunological infertility. Intention-to-treat analyses were not performed

Selective reporting (reporting bias)Low riskProtocol was not reviewed, but outcomes in the methods and results sections are similar

Other biasUnclear riskBaseline characteristics for both groups are reported, but no mention is made of similarity between groups nor results of any statistical comparison of homogeneity

Knuth 1987

MethodsCountry of study: Germany

Number of centres: single centre

Consent: reported

Ethical approval: not reported

Timing of trial: not reported

Source of funding: HMG/HCG and placebo preparations were offered by Serono Co

Numbers of participants

  • Recruited: 44 (5 refused participation)
  • Randomly assigned: 39 (19 treatment group and 20 placebo group)
  • Excluded: 2 because of development of febrile illness (treatment group) excluded from seminal parameters analysis but not from pregnancy analysis
  • Lost to follow-up: none in pregnancy analysis
  • Analysed: 39


ParticipantsPre-allocation examinations and studies: assessment of endocrine parameters using 100 mcg GnRH and 10 mg metoclopramide monohydrochloride iv tests. Evaluation of Leydig cell responsiveness using 5000 IU hCG IM injection at the end of the GnRH test

Inclusion criteria

  • Subfertile men with sperm count between 0.1 and 10 Mil/mL on 2 occasions
  • Basal FSH, LH and testosterone are normal
  • No treatment for 6 months
  • Female partners had no recognisable cause of infertility with normal tubal patency and ovulatory function


Exclusion criteria

  • Men with known cause of infertility


Age: in placebo group 33.2 years; in treatment group 31.1 years
Duration of follow-up: 6 months (13 weeks' treatment and 3 months' follow-up)


InterventionsTreatment group: 150 IU hMG (Pregonal, Serono) three times per week in addition to 2500 IU hCG (Pregnesin, Serono) twice weekly or 13 weeks. Injections were given by the participant's general practitioner
Control group: same schedule of injections with NaCl injections for 13 weeks (labelled ampoules in a double-blind design)
Duration of intervention: 13 weeks
Follow-up examinations: semen parameters and basal LH, FSH and testosterone levels were assessed 1 week after the last injection and were repeated three more times at monthly intervals


OutcomesPrincipal and secondary: semen parameters and pregnancy rate
Methods of assessing outcome measures: not reported
Adverse events: 1 in the treatment group developed side effects (temporary breast tenderness and gynaecomastia that resolved spontaneously within the treatment period)


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAuthors reported that the trial was a randomised trial and provided no further details

Allocation concealment (selection bias)Unclear riskAuthors did report on allocation concealment

Blinding (performance bias and detection bias)
All outcomes
Low riskAuthors reported that the trial was a double-blind trial that included the use of an appropriate placebo

Incomplete outcome data (attrition bias)
All outcomes
Low riskTwo participants in the treatment group dropped out because they developed febrile illness. They were excluded from seminal parameters analysis but not from pregnancy analysis

Selective reporting (reporting bias)Low riskProtocol was not reviewed, but outcomes in the methods and results sections are similar

Other biasLow riskBaseline hormone characteristics for both groups were reported to be similar

Matorras 1997

MethodsCountry of study: Spain

Number of centres: single centre

Consent: reported

Ethical approval: not reported

Timing of trial: January 1991 to December 1994

Source of funding: not reported

Numbers of participants

  • Recruited: 148
  • Randomly assigned: 148 (68 treatment group and 80 placebo group)
  • Excluded: 12 participants were excluded (six before the beginning of IUI, three in cancelled cycles (two because of hyperstimulation risk, one because of insufficient response), one in a spontaneous ovarian cycle without IUI (corresponding to vacations) and two after concluding the sixth IUI cycle)
  • Lost to follow-up: not reported
  • Analysed: 136


ParticipantsPre-allocation examinations and studies:

  • Female partner pelvic examination, including HSG or ultrasound, blood chemistry, endometrial biopsy, plasma progesterone and prolactin measurements; postcoital test
  • Male partner: semen analysis and hormone analysis


Inclusion criteria

  • Infertility history 2 years
  • Semen preparation with Percoll to obtain at least 2 × 106 motile spermatozoa/mL


Exclusion criteria

  • Males with low FSH concentrations


Age: 34.06 years in FSH group versus 34.63 years in control group

Duration of follow-up: up to 6 cycles of IUI


InterventionsTreatment group: IM injections of 150 IU pure urinary FSH (Fertinorm; Serono in the first 2 years of study) and SC 150 IU highly purified FSH (Neo-Fertinorm; Serono in the second 2 years of study) three times per week starting 3 months before the first IUI cycle and ending with the fifth IUI cycle
Control group: no treatment for males and same treatment as treatment group for females
Female partners: no IUI was performed in the first 3 months after randomisation in either group. Then all women underwent ovarian stimulation (with HMG or FSH) and were monitored by vaginal US and E2 levels. HCG administration and IUI with luteal phase supplementation with HCG or micronized progesterone were performed up to 5 cycles
Duration of intervention: 3 months before IUI and up to 5 months (5 IUI cycles) during IUI
Follow-up examinations: A second sperm analysis was performed after 3 months of therapy in the FSH group and after 3 months of no treatment in the non-FSH group


OutcomesPrincipal and secondary: clinical pregnancy rate and post-FSH semen parameters

Methods of assessing outcome measures: ultrasound identification of an embryonic sac at 6 to 7 weeks amenorrhoea and semen analysis

Adverse events: none reported in the FSH group. One participant in the control group suffered an intracranial haemorrhage


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskAuthors reported randomly assigning participants using an "alleatory number table"

Allocation concealment (selection bias)Unclear riskAuthors did report on allocation concealment

Blinding (performance bias and detection bias)
All outcomes
High riskAuthors reported that the study was not double-blind, nor was a placebo used in the control group (open-label trial design)

Incomplete outcome data (attrition bias)
All outcomes
Low riskAuthors excluded 12/148 participants and provided reasons. Intention-to-treat analysis was not performed

Selective reporting (reporting bias)Low riskProtocol was not reviewed, but outcomes in the methods and results sections are similar

Other biasLow riskBaseline characteristics for both groups were reported to be similar

Paradisi 2006

MethodsCountry of study: Italy

Number of centres: single centre

Consent: reported

Ethical approval: reported

Timing of trial: not reported

Source of funding: supported in part by grants from Ministero dell’Istruzione, dell’Università e della Ricerca, Rome, Italy, and from Serono Industries, Rome, Italy

Numbers of participants

  • Recruited: not reported
  • Randomly assigned: 30
  • Excluded: 0
  • Lost to follow-up: 0
  • Analysed: 30


ParticipantsPre-allocation examinations and studies

Inclusion criteria

  • Male partner: history of unexplained male factor subfertility of 2 years' duration with no indication of hormonal (normal basal FSH and T values), infective (negative sperm culture) or physical causes for their subfertility
  • Female partner: no endocrine and/or obstructive disorders


Exclusion criteria: testicular tumour, hypergonadotropic hypogonadism, hypogonadotropic hypogonadism, isolated gonadotropin deficiency, hyperprolactinaemia, severe scrotal varicocele, history of cryptorchidism, leucocytospermia, acute orchitis and other genital infections, positivity to seminal sperm antibodies, presence of Y chromosome microdeletions, obesity and other systemic severe chronic illness

Age: not reported

Duration of follow-up: not reported


InterventionsTreatment group: 300 IU rhFSH SC every other day for >4 months
Control group: placebo
Duration of intervention: >4 months
Follow-up examinations: semen and hormone analyses


OutcomesPrincipal and secondary: semen and hormone profile, clinical pregnancy and live birth rates

Methods of assessing outcome measures: semen and hormone analyses immediately after treatment; follow-up of pregnancies

Adverse events: none reported


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskAuthors reported using a "computer-generated randomization list"

Allocation concealment (selection bias)Unclear riskAuthors did report on allocation concealment

Blinding (performance bias and detection bias)
All outcomes
Low riskAuthors reported that the trial was double-blind and used identical placebos

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts were reported. All 30 participants were analysed

Selective reporting (reporting bias)Low riskProtocol was not reviewed, but outcomes in the methods and results sections are similar

Other biasLow riskBaseline characteristics for both groups were reported to be similar

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Ashkenazi 1999Quasi-randomised trial

Ben-Rafael 2000Partial cross-over study with no data before cross-over

Bouloux 2003No outcomes of importance to this review were reported

Caroppo 2003Prospective cohort study

Dirnfeld 2000Retrospective cohort study

Foresta 1998No outcomes of importance to this review were reported

Foresta 2002No outcomes of importance to this review were reported

Iacono 1996No outcomes of importance to this review were reported

Thomalla-Sauter 2001Non-randomised controlled trial

 
Comparison 1. Gonadotrophins versus placebo/no treatment for the treatment of idiopathic male subfertility

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Live birth rate per couple1Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only

    1.1 Live birth rate per couple
130Peto Odds Ratio (Peto, Fixed, 95% CI)9.31 [1.17, 73.75]

 2 Pregnancy rate per couple6Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only

    2.1 Spontaneous pregnancy rate per couple
5412Peto Odds Ratio (Peto, Fixed, 95% CI)4.94 [2.13, 11.44]

    2.2 Pregnancy rate per couple after ICSI
144Peto Odds Ratio (Peto, Fixed, 95% CI)1.93 [0.52, 7.20]

    2.3 Pregnancy rate per couple after IUI
1148Peto Odds Ratio (Peto, Fixed, 95% CI)1.05 [0.38, 2.89]

 3 Subgroup analysis: Pregnancy rate per couple with no female factor5Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only

    3.1 Spontaneous pregnancy rate per couple with no female factor
4264Peto Odds Ratio (Peto, Fixed, 95% CI)5.00 [1.88, 13.34]

    3.2 Pregnancy rate per couple after ICSI with no female factor
144Peto Odds Ratio (Peto, Fixed, 95% CI)1.93 [0.52, 7.20]

 
Summary of findings for the main comparison. Gonadotrophins versus placebo/no treatment for the treatment of idiopathic male subfertility for idiopathic male factor subfertility

Gonadotrophins versus placebo/no treatment for the treatment of idiopathic male subfertility

Population: Men with idiopathic male factor subfertility

Setting: Assisted reproduction

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Placebo/no treatment for the treatment of idiopathic male subfertilityGonadotrophins

Live birth rate per couple randomly assigned0 per 10000 per 1000
(0 to 0)
OR 9.31
(1.17 to 73.75)
30
(1 study)
⊕⊝⊝⊝
very low1,2

Spontaneous pregnancy rate per couple randomly assigned14 per 100067 per 1000
(30 to 142)
OR 4.94
(2.13 to 11.44)
412
(5 studies)
⊕⊕⊕⊝
moderate3

*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio.

GRADE Working Group grades of evidence:
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1Authors did not report on allocation concealment.
2Only one included trial (i.e. inconsistency cannot be assessed).
3All trials suffered from at least one potential risk of bias.