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Intrauterine insemination versus fallopian tube sperm perfusion for non-tubal infertility

  1. Astrid EP Cantineau1,*,
  2. Ben J Cohlen2,
  3. Maas Jan Heineman3,
  4. Jane Marjoribanks4,
  5. Cindy Farquhar4

Editorial Group: Cochrane Gynaecology and Fertility Group

Published Online: 30 OCT 2013

Assessed as up-to-date: 12 SEP 2013

DOI: 10.1002/14651858.CD001502.pub4


How to Cite

Cantineau AEP, Cohlen BJ, Heineman MJ, Marjoribanks J, Farquhar C. Intrauterine insemination versus fallopian tube sperm perfusion for non-tubal infertility. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD001502. DOI: 10.1002/14651858.CD001502.pub4.

Author Information

  1. 1

    University Medical Centre, Department of Obstetrics & Gynaecology, Groningen, Netherlands

  2. 2

    Isala Clinics, Location Sophia, Department of Obstetrics & Gynaecology, Zwolle, Netherlands

  3. 3

    University of Amsterdam, Department of Obstetrics & Gynaecology Academic Medical Centre, Amsterdam, Netherlands

  4. 4

    University of Auckland, Obstetrics and Gynaecology, Auckland, New Zealand

*Astrid EP Cantineau, Department of Obstetrics & Gynaecology, University Medical Centre, Hanzeplein 1, Groningen, 9700 RB, Netherlands. aepcantineau@gmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 30 OCT 2013

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

MethodsRandomisation: blocked computer-generated sequence of numbers

Trial design: cross-over

Concealment of allocation: adequate


ParticipantsParticipants: 56 women; 127 cycles

Age of women: 33.2 ± 4.3 years for the total group

Duration of subfertility: total group 2.4 ± 1.3 years

Type of subfertility: unexplained subfertility (not further defined—mean duration of infertility 2.4 years)


InterventionsStimulation method: rFSH 75 IU from CD 3

Intervention: IUI or FSP 35 to 37 hours after hCG, with husband's semen

Semen preparation: swim-up

Catheter used: IUI: Kremer de la Fontaine
FSP: Foley catheter

Maximum number of cycles per couple: 4


OutcomesClinical pregnancy per couple
Multiple pregnancy
Miscarriage


NotesAdditional details received from authors. Pre-cross-over data available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated sequence of numbers blind to the operators

Allocation concealment (selection bias)Low riskAdequate

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding not reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskPre-cross-over data reported for all randomised participants (n = 56)

Selective reporting (reporting bias)Unclear riskLive birth not reported. OHSS not reported

Other biasLow riskNo other potential source of bias noted

El Sadek 1998

MethodsRandomisation: block randomisation list

Trial design: parallel

Concealment of allocation: adequate


ParticipantsParticipants: 96 women; 100 cycles

Age of women: IUI 31.5 ± 5.3 years; FSP 32.0 ± 5.2 years

Duration of subfertility: IUI 8.6 ± 2.1 years; FSP 7.3 ± 1.9 years

Type of subfertility: unexplained subfertility, light peritubal adhesions*, PCO, cervical hostility

*19% of participants with light peritubal adhesions or slightly reduced tubal fimbriae and/or moderate loss of gracility of the tubes. Women with obstructed tubes excluded


InterventionsStimulation method: CC or CC + hMG + hCG

Intervention: IUI or FSP 34 to 36 hours after hCG, with husband's semen

Semen preparation: swim-up

Catheter used: Frydman catheter (with Allis clamp for FSP)

Maximum number of cycles per couple: not stated


OutcomesLive birth
Clinical pregnancy
Multiple pregnancy
Miscarriage


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Blocked randomization list"

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding not reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskData reported for all randomised participants (n = 96)

Selective reporting (reporting bias)Low riskReported live birth and adverse events

El-Khayat 2012

MethodsRandomisation: computer-generated random numbers

Trial design: parallel

Concealment of allocation: adequate


ParticipantsParticipants: 120 women

Age of women: mean 29 years

Duration of subfertility: mean 3.4 to 3.6 years

Type of subfertility: mild to moderate male factor infertility, defined as sperm count less than 15 × 106/mL, total motility less than 40% or normal forms less than 4%—per WHO criteria. Patients with severe oligospermia (<5 × 106/mL) excluded


InterventionsStimulation method: CC + hMG

Intervention: IUI or FSP 34 to 36 hours after hCG, with partner's semen

Semen preparation: double-wash and swim-up

Catheter used: insulin syringe attached to an artificial insemination catheter for IUI; pediatric Foley catheter for FSP

Maximum number of cycles per couple: not stated


OutcomesClinical pregnancy (positive β-hCG test confirmed by ultrasound)
Multiple pregnancy
Miscarriage


NotesAuthor sent data on allocation concealment and live birth by personal communication 4.4.13


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random numbers

Allocation concealment (selection bias)Low risk"Closed sealed consecutively numbered opaque envelopes" (personal communication with author)

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskData reported for all randomised participants (n = 120)

Selective reporting (reporting bias)Low riskReported live birth and adverse events

Other biasLow riskNo other potential source of bias noted

Fanchin 1995

MethodsRandomisation: block randomisation list

Power analysis: not stated

Trial design: parallel

Concealment of allocation: not stated


ParticipantsParticipants: 74 women; 100 cycles

Age of women: IUI 31.8 ± 4.6 years; FSP 31.8 ± 3.7 years

Duration of subfertility: IUI 3.6 ± 1.2; FSP 3.4 ± 1.1 years

Type of subfertility: partial tube damage*, idiopathic, cervical, ovulatory

*37% of women with partial tube damage. Women with severe tubal damage or obstructed tubes excluded


InterventionsStimulation method: (1) CC + hMG; (2) hMG alone; (3) FSH, hMG and GnRH agonist
All followed by hCG

Intervention: IUI or FSP 36 hours after hCG with husband's semen

Sperm preparation: Percoll gradient

Catheter used: Frydman catheter for IUI and FSP with FAST system

Maximum number of cycles per couple: not stated


OutcomesPregnancy
Multiple pregnancy
Miscarriage


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskBlocked randomisation list

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskBlinding not reported

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskData reported for all cycles, but number of women in each group not reported

Selective reporting (reporting bias)Unclear riskNot stated

Other biasUnclear riskUnit of analysis error—women randomised, but data reported per cycle. 37% of women had mild tubal damage

Farquhar 2013

MethodsRandomisation: block randomisation list

Trial design: parallel

Concealment of allocation: serial numbered opaque sealed envelopes

Pragmatic multicentred study design


ParticipantsParticipants: 417 women; one cycle each

Age of women: IUI 33.67 ± 4.87; FSP 34.23 ± 4.62 years

Duration of subfertility: (median) IUI 24 (IQR 9 to 42); FSP 24 (IQR 11 to 36) months

Type of subfertility: non-tubal infertility, 10% donor cycles


InterventionsStimulation method: CC or FSH or letrozole (10% were unstimulated)

Intervention: IUI or FSP 34 to 36 hours after hCG, with husband's semen

IUI Catheter: Tomcat or Wallace catheter used for the IUI procedure. Inseminate prepared using a density gradient (Puresperm), and spermatozoa re-suspended in 0.5 mL of medium, as used in the recruiting centre. Catheter passed gently through the cervical canal high up into the uterus, and specimen with a volume of 0.5 mL slowly injected according to standard unit protocol

FSP catheter: atraumatic insemination catheter (Cook catheter J-CHSG-503000) used for the FSP procedure

Sperm preparation: inseminate prepared using a density gradient (Puresperm), and spermatozoa re-suspended in 4 mL of human tubal fluid or equivalent medium, as used in the recruiting centre. Catheter attached to a 5-mL syringe

Maximum number of cycles per couple: one


OutcomesLive birth
Pregnancy
Multiple pregnancy
Miscarriage

Ectopic pregnancy


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"computer-generated randomisation sequence of random blocks of 3 different sizes, chosen randomly (with equal probability of getting 6, 8 or 10 in each block)"

Allocation concealment (selection bias)Low risk"Allocation numbers were placed in individual, sealed, opaque envelopes that were numbered sequentially"

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo blinding

Incomplete outcome data (attrition bias)
All outcomes
Low risk6 withdrawals and 1 missing data

Selective reporting (reporting bias)Low riskNo major protocol changes in outcomes

Other biasLow riskNo other potential source of bias noted

Filer 1996

MethodsRandomisation: computer-generated algorithm

Power analysis: not stated

Trial design: cross-over

Concealment of allocation: adequate


ParticipantsParticipants: 106 cycles

Age of women: < 40 years

Duration of subfertility: at least one year

Type of subfertility: unexplained


InterventionsStimulation method: not stated

Intervention: IUI or FSP 36 to 42 hours after hCG

Sperm preparation: Percoll gradient

Catheter used: Makler cannula for IUI and FSP

Maximum number of cycles per couple: 6


OutcomesPregnancy


NotesAdditional details received from authors


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated algorithm

Allocation concealment (selection bias)Low riskAfter additional information from the author

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo blinding reported

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskData reported per cycle only—number of couples not reported

Selective reporting (reporting bias)Unclear riskAdverse events not reported

Other biasHigh riskNo pre-cross-over data reported. Limited information, as study available only as abstract

Furuya 2010

MethodsRandomisation: not stated

Power analysis: not stated

Trial design: parallel

Concealment of allocation: not stated


ParticipantsParticipants: 158 women, 322 cycles

Age of women: not stated

Duration of subfertility: not stated

Type of subfertility: non-tubal infertility


InterventionsStimulation method: not stated

Intervention: IUI or FSP

Sperm preparation: not stated

Catheter used: not stated

Maximum number of cycles per couple: 3


OutcomesPregnancy


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskStates "they were randomised" ... no further details

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo blinding reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskResults reported for all randomised women (n = 158)

Selective reporting (reporting bias)Unclear riskLive birth and adverse effects not reported.

Other biasUnclear riskLimited reporting—abstract available only

Gregoriou 1995

MethodsRandomisation: list of random numbers

Trial design: parallel

Concealment of allocation: adequate


ParticipantsParticipants: 60 women; 150 cycles

Age of women: IUI 30.4 ± 3.5 years; FSP 30.3 ± 3.6 years

Duration of subfertility: IUI 6.5 ± 2.1 years; FSP 6.3 ± 2.5 years

Type of subfertility: unexplained subfertility

Mean duration of unexplained infertility 6.5 years (range 2 to 12 years)


InterventionsStimulation method: hMG 75 IU from CD 3

Intervention: IUI or FSP 36 hours after hCG with husband's semen

Sperm preparation: two-layer Percoll gradient

Catheter used: Makler device for IUI and Frydman catheter (with Allis clamp) for FSP

Maximum number of cycles per couple: 3


OutcomesPregnancy


NotesAdditional details received from authors


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskList of random numbers

Allocation concealment (selection bias)Low riskAdequate

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo blinding reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcomes reported for all women randomised (n = 60)

Selective reporting (reporting bias)Unclear riskLive birth not reported, adverse effects not reported

Other biasUnclear riskNumber of motile sperm inseminated was significantly higher in the FSP group

Kahn 1993

MethodsRandomisation method: not stated

Trial design: parallel

Concealment of allocation: sealed envelopes

Power analysis: not stated


ParticipantsParticipants: 60 women; 103 cycles

Age of women: IUI 31.8 ± 0.8 years; FSP 31.7 ± 0.6 years

Duration of subfertility: > 3 years

Type of subfertility: unexplained infertility

Minimum duration of unexplained infertility 3 years (range 3 to 6 years)


InterventionsStimulation method: CC + hMG + hCG

Intervention: IUI or FSP 34 to 37 hours after hCG with husband's semen

Semen preparation: swim-up

Catheter used: Frydman catheter (with Allis clamp for FSP)

Maximum number of cycles per couple: 3


OutcomesClinical pregnancy per woman
Multiple pregnancy
Treatment complications
Miscarriage


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"The women were randomized for treatment with IUI or FSP on the day of HCG administration, by drawing a sealed envelope". No further details provided

Allocation concealment (selection bias)Unclear riskAs above

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo blinding reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskResults reported for 58/60 women randomised (97%). Two women dropped out in IUI group—reasons explained

Selective reporting (reporting bias)Unclear riskLive birth not reported

Other biasLow riskNo other potential source of bias noted

Kamel 1999

MethodsRandomisation method: not stated

Trial design: cross-over

Concealment of allocation: not reported


Participants120 couples, moderate male factor infertility (not further defined)


InterventionsStimulation method: CC 100 mg from day 3 to 8 when one follicle reached 18 mm

Intervention: IUI with 0.5 mL of the sample or FSP 4 mL injected intrauterine under pressure after closure of the cervix with husband's semen

Semen preparation: swim-up

Catheter used: Frydman catheter (with Allis clamp for FSP)

Maximum number of cycles per couple: 3 (on one treatment)


OutcomesPregnancy for pre-cross-over and post-cross-over data


NotesCrossover: if no pregnancy occurred, method of insemination changed to that of the other group 3 months later


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskStates "random cross-over study"—no further details

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo blinding reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskResults reported for all women randomised (n = 120)

Selective reporting (reporting bias)Unclear riskLive birth and adverse effects not reported

Other biasUnclear riskLimited reporting—abstract available only

Ng 2003

MethodsRandomisation method: computer-generated randomisation list

Trial design: parallel

Concealment of allocation: not stated

Follow-up: 3 cycles

Power analysis: yes

Intention-to-treat analysis: not performed


ParticipantsParticipants: 90 women; 204 cycles
(1) IUI 30 women, 68 cycles; (2) IUI 30 women, 76 cycles; and (3) FSP 30 women, 59 cycles

Age of women: (1) IUI 32.7 ± 2.4 years; (2) IUI 32.9 ± 2.7 years

Duration of subfertility: (1) IUI 4.4 ± 1.7; (2) IUI 4.2 ± 2.1 years

22/90 women had secondary infertility

Type of subfertility: male factor (37%), unexplained subfertility and endometriosis

Male subfertility not defined. All participants had > 10 million sperm in ejaculate during workup


InterventionsStimulation method: 150 IU hMG from CD 3, dosage titrated later according to ovarian response; 10.000 IU hCG (1) IUI 38 hours after hCG; (2) FSP 38 hours after hCG; (3) IUI 18 and 38 hours after hCG with partner's semen (Group 3 data not included in this review)

Sperm preparation: density gradient centrifugation method

IUI procedure: 0.3 to 0.5 mL
Tomcat catheter for IUI and intrauterine injectors (ZUOI-2) for FSP

Maximum number of cycles per couple: 3


OutcomesClinical pregnancy per couple

Miscarriage

Multiple pregnancy


NotesLuteal support with 1500 IU hCG on day 5 and day 10 after hCG


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated randomisation list

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo blinding reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcomes reported for all randomised women (n = 90)

Selective reporting (reporting bias)Unclear riskLive birth not reported

Other biasUnclear riskTotal motile sperm count in first insemination significantly different between IUI group and FSP group

Noci 2007

MethodsRandomisation method: randomisation tables

Trial design: three parallel arms—FSP, IUI and intraperitoneal insemination (IPI)—three cycles

Concealment of allocation: not stated

Power analysis: not stated

Intention-to-treat analysis: not performed


ParticipantsParticipants: 71 couples; 101 cycles
(1) IUI 23 women, 34 cycles; (2) FSP 24 women, 33 cycles; and (3) IPI 24 women, 34 cycles (Group 3 data not included in this review)

Age of women: (1) IUI 33.7 ± 1.6 2 years; (2) FSP 35.3 ± 3 years; and (3) IPI 35.3 ± 4.4 years

Duration of subfertility: (1) IUI 3.4 ± 1.6 years; (2) FSP 3.3 ± 1.9 years; and (3) IPI 3.3 ± 1.4 years

Type of subfertility: male (not further defined), unexplained subfertility; and endometriosis, mixed


InterventionsStimulation method: recombinant or urinary FSH, dosage titrated later according to the ovarian response; 10,000 UI of hCG administered when 1 follicle > 18 mm and 2 others > 16 mm

Sperm preparation: discontinuous density gradient centrifugation method (PureSperm)

IUI procedure: Frydman catheter 0.3 to 0.5 mL

FSP using a hysterosalpingography (Cervix Adaptor) catheter

IPI: direct 2 mL sperm preparation injected into posterior vaginal fornix by a 19-gauge 2.2-cm needle

Maximum number of cycles per couple: 3


OutcomesClinical pregnancy

Multiple pregnancy


NotesAll pregnancies occurred on first cycle


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Couples were randomized by predefined tables of randomization"

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo blinding reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcomes reported for all randomised participants (n = 71)

Selective reporting (reporting bias)Unclear riskLive birth not reported. Miscarriage not reported

Other biasLow riskNo other potential source of bias noted

Nuojua-Huttunen 1997

MethodsRandomisation: computer-generated random numbers

Trial design: parallel

Concealment of allocation: not stated

Power analysis: yes


ParticipantsParticipants: 100 women; 100 cycles

Age of women: IUI 31.1 ± 4.0 years; FSP 30.2 ± 4.4 years

Duration of subfertility: IUI 3.8 ± 2.2 years; FSP 2.9 ± 1.7 years

Type of subfertility: male subfertility, unexplained subfertility, mild endometriosis, ovarian dysfunction

Duration of unexplained infertility not reported

Male subfertility defined as sperm quality before treatment normal or slightly abnormal (> 10 × 106 sperm per mL, > 40% progressive motility [grade A + B], > 30% normal forms and after a Percoll preparation > 1 × 106 progressively motile sperm per mL)


InterventionsStimulation method: CC + hMG + hCG

Intervention: FSP or IUI 36 hours after hCG, type of semen not stated

Semen preparation: Percoll gradient

Catheter used: Kremer de la Fontaine for IUI; Foley catheter for FSP

Maximum number of cycles per couple: 1


OutcomesClinical pregnancy per woman
Multiple pregnancy
Miscarriage
OHSS


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random numbers

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo blinding reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcomes reported for all randomised participants (n = 100)

Selective reporting (reporting bias)Unclear riskLive birth not reported

Other biasLow riskNo other potential source of bias noted

Papier 1998

MethodsRandomisation: computer-generated random numbers

Trial design: parallel

Concealment of allocation: adequate

Power analysis: no


ParticipantsParticipants: 100 women; 87 cycles

Age of women: not stated

Duration of subfertility: at least one year

Type of subfertility: mild male subfertility, unexplained subfertility


InterventionsStimulation method: hMG from CD 5 + hCG

Intervention: FSP 34 hours after hCG and IUI 38 hours after hCG; type of semen not stated

Semen preparation: Percoll gradient

Catheter used: Frydman for IUI; Makler cannula for FSP

Maximum number of cycles per couple: 1


OutcomesPregnancy


NotesLuteal support with 400 mg progesterone. Additional details received from authors


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated random numbers

Allocation concealment (selection bias)Low riskAdequate

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo blinding reported

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk16 participants did not undergo intervention (reasons given), but intention to treat analysis possible (assuming no pregnancy in those 16 women)

Selective reporting (reporting bias)Unclear riskNot stated

Other biasLow riskNo other potential source of bias noted

Ricci 2001

MethodsRandomisation: random number generator on computer

Trial design: parallel

Concealment of allocation: not stated

Power analysis: yes


ParticipantsParticipants: 65 women; 132 cycles

Age of women: IUI 34.8 ± 4.6 years; FSP 35.5 ± 3.5 years

Duration of subfertility: IUI 3.5 ± 1.4 years; FSP 3.4 ± 1.3 years

Type of subfertility: unexplained infertility for 2 years


InterventionsStimulation method: u-hFSH + hCG

Intervention: IUI and FSP 36 hours after hCG with husband's semen

Semen preparation: swim-up

Catheter used: Frydman catheter for IUI; FAST system for FSP

Maximum number of cycles per couple: 3


OutcomesOngoing pregnancy
Multiple pregnancy


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number generator on computer

Allocation concealment (selection bias)Unclear riskNo details reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo blinding reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo losses to follow-up

Selective reporting (reporting bias)Unclear riskNot stated

Other biasLow riskNo other potential source of bias noted

Trout 1999

MethodsRandomisation: random number generator

Trial design: parallel

Concealment of allocation: third party

Power analysis: yes


ParticipantsParticipants: 268 women; 268 cycles

Age of women: IUI 33.0 ± 2.7 years; FSP 33.0 ± 2.5 years

Duration of subfertility: not stated

Type of subfertility: ovulation dysfunction, unexplained infertility, male factor, endometriosis, cervical mucus factor, multiple diagnosis


InterventionsStimulation method: CC + gonadotropins or gonadotropins alone + hCG

Intervention: IUI or FSP 36 hours after hCG with husband's semen

Semen preparation: Percoll gradient

Catheter used: IUI catheter for IUI; ZUI II catheter for FSP

Maximum number of cycles per couple: not stated


OutcomesClinical pregnancy
Ectopic pregnancy


NotesDuration of infertility unknown


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom number generator

Allocation concealment (selection bias)Low riskStates, "Neither the physicians enrolling the patients nor the physicians performing the inseminations had access to the randomization schedule"

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo blinding reported

Incomplete outcome data (attrition bias)
All outcomes
Low riskData reported for all women who received interventions, but does not clearly state how many women randomised, so unclear whether any dropped out

Selective reporting (reporting bias)Unclear riskDoes not report live birth, miscarriage or OHSS

Other biasLow riskNo other potential source of bias noted

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Allahbadia 1998Randomisation method was not stated, and the groups were not equal (369 in IUI group and 20 in FSP group), which makes adequate randomisation impossible. The author did not reply to our request for further information. Duration of subfertility was not stated

Arroyo Vieyra 1995Randomisation method was not stated, and the groups were not equal (95 cycles with IUI and 36 cycles with FSP), which makes adequate randomisation improbable. The author did not reply to our request for further information

Ciftci 1998The trial was quasi-randomised. The duration of subfertility was not stated. The author gave additional information regarding data after the first cycle. However, these data consisted of only pregnancies per cycle. Moreover, no data were available on the duration of subfertility

Desai 1998Randomisation method was not stated, but the groups were not equal (369 in IUI group and 20 in FSP group), which makes adequate randomisation improbable. The author did not reply to our request for further information. The duration of subfertility was not stated

Dodson 1998The trial did not perform the comparison of interest

Elhelw 2000Letter
Publication did not perform the comparison of interest

Fanchin 1996Letter
Publication did not perform the comparison of interest

Fanchin 1997Letter
Publication did not perform the comparison of interest

Kahn 1992Cohort study

Kahn 1992aCohort study

Kahn 1993aThis study did not perform the comparison of interest

Karande 1995Both IUI and FSP were performed on two consecutive days after hCG administration. A substantial number of women with tubal subfertility were included. The duration of subfertility was not stated

Levitas 1999This study did not perform the comparison of interest

Li 1993Case report that described a simple non-invasive method of fallopian tube sperm perfusion. This study did not perform the comparison of interest

Maheshwari 1998The trial was quasi-randomised

Mamas 1996The trial was quasi-randomised

Mamas 2006The trial did not perform the comparison of interest. Intrauterine tuboperitoneal insemination is not the same as fallopian tube sperm perfusion

Posada 2005The trial did not perform the comparison of interest

Prietl 1999This study compared conventional IUI with intra-tubal insemination, which is different from perfusion of the fallopian tubes (FSP)

Shekhawat 2012The method of allocation was not random and used odd and even numbers of the ART register to assign FSP and IUI. Confirmed in writing by author

Soliman 1999The trial was a non-controlled randomised trial

Soliman 2005The trial did not perform the comparison of interest

 
Characteristics of studies awaiting assessment [ordered by study ID]
Ricci 2008

MethodsRCT

Participants400 couples with unexplained or mild male factor infertility

InterventionsIUI versus FSP in natural cycles

OutcomesClinical pregnancy, ectopic pregnancy, miscarriage

NotesStudy completed December 2009. Emailed lead investigator March 2013—no response to date

 
Comparison 1. IUI versus FSP

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

 1 Live birth per couple3633Odds Ratio (M-H, Fixed, 95% CI)0.94 [0.59, 1.49]

 2 Clinical pregnancy per couple14Odds Ratio (M-H, Random, 95% CI)Subtotals only

 3 Multiple pregnancy8Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 Multiple pregnancy per couple
7908Odds Ratio (M-H, Fixed, 95% CI)0.62 [0.29, 1.32]

    3.2 Sensitivity analysis: multiple pregnancy per pregnancy
8197Odds Ratio (M-H, Fixed, 95% CI)0.96 [0.44, 2.07]

 4 Miscarriage rate7Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    4.1 Miscarriage per couple
7884Odds Ratio (M-H, Fixed, 95% CI)1.07 [0.56, 2.05]

    4.2 Miscarriage per pregnancy
7180Odds Ratio (M-H, Fixed, 95% CI)1.32 [0.63, 2.78]

 5 Ectopic pregnancy4Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    5.1 Ectopic pregnancy per couple
4643Odds Ratio (M-H, Fixed, 95% CI)0.88 [0.24, 3.19]

    5.2 Ectopic pregnancy per pregnancy
4111Odds Ratio (M-H, Fixed, 95% CI)1.71 [0.42, 6.88]

 
Comparison 2. IUI versus FSP subgroups by indication

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

 1 Unexplained subfertility7378Odds Ratio (M-H, Fixed, 95% CI)0.63 [0.39, 1.02]

    1.1 Clinical pregnancy
7378Odds Ratio (M-H, Fixed, 95% CI)0.63 [0.39, 1.02]

 2 Mild to moderate male factor subfertility5Odds Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Live birth
1120Odds Ratio (M-H, Fixed, 95% CI)0.40 [0.14, 1.14]

    2.2 Clinical pregnancy
5303Odds Ratio (M-H, Fixed, 95% CI)0.53 [0.28, 1.01]

 
Summary of findings for the main comparison. IUI compared with FSP for non-tubal infertility

IUI compared with FSP for non-tubal infertility

Patient or population: women with non-tubal infertility
Settings: subfertility clinic
Intervention: intrauterine insemination
Comparison: fallopian tube sperm perfusion

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

Assumed riskCorresponding risk

FSPIUI

Live birth per couple133 per 1000126 per 1000
(83 to 186)
OR 0.94
(0.59 to 1.49)
633
(3 studies)
⊕⊕⊝⊝
low1,2

Clinical pregnancy per couple185 per 1000145 per 1000
(100 to 202)
OR 0.75
(0.49 to 1.12)
1745
(14 studies)
⊕⊕⊝⊝
low3,4

Multiple pregnancy per couple70 per 100055 per 1000
(33 to 91)
OR 0.62
(0.29 to 1.32)
908
(7 studies)
⊕⊕⊝⊝
low2,3

Miscarriage per couple43 per 100046 per 1000
(24 to 84)
OR 1.07
(0.56 to 2.05)
884
(7 studies)
⊕⊕⊝⊝
low2,3

Ectopic pregnancy per couple10 per 10008 per 1000
(2 to 30)
OR 0.88
(0.24 to 3.19)
643
(4 studies)
⊕⊝⊝⊝
very low2,3,5

*The basis for the assumed risk (the median control group risk across studies) is provided in footnotes. 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.

 1One of the three studies did not describe method of allocation concealment and 19% of women in this study had mild tubal damage.
2Imprecision: Confidence intervals cross the line of no effect and do not exclude an appreciable benefit or harm.
3Most studies failed to provide adequate details of methods of sequence generation and allocation concealment.
4Unexplained statistical heterogeneity (I2 = 52%).
5Very serious imprecision.
 
Table 1. Per cycle data

StudyClinical pregnancy per cycle


IUIFSPP value

Fanchin 199510/50 (20%)20/50 (40%)P < 0.04

Filer 199612/59 (20%)5/47 (11%)P > 0.05