10Intrauterine insemination in unexplained infertility: gonadotrophins

StudyPopulationInterventionOutcomesResultsCommentsStudy typeEL
Hughes 199769122 RCTs (5214 cycles)

Women with unexplained infertility
FSH/IUI versus FSH/timed intercourse (8 RCTs)Pregnancy rateSignificant improvement with FSH/IUI: OR 2.37 (CI 1.43 to 3.90) FSH: OR 2.35 (CI 1.87 to 2.94) IUI: OR 2.82 (CI 2.18 TO 3.66) Male factor: OR 0.48 (CI 0.37 to 0.61)
Endometriosis: OR 0.45 (CI 0.27 to 0.76)
Clinical heterogeneitySR1a
Zeyneloglu et al. 19986907 RCTs (431 cycles)

Women with unexplained infertility
Gonadotrophins/IUI versus gonadotrophins onlyPregnancy rateSignificant improvement with gonadotrophins/IUI: OR 1.84 (CI 1.30 to 2.62)SR1a
Ford et al. 19976847 RCTs (934 cycles)

Women with unexplained infertility
IUI versus timed intercourse versus ICI +gonadotrophins (4 trials) +CC (2 trials) + no stimulation (3 trials)Pregnancy rateNo significant differences overall: OR 1.5 (CI 1.0 to 2.2)

Significant improvement with gonadotrophins in IUI/Ttimed intercourse/ICI: RR 2.17 (CI 1.10 to 4.28; NTT 11 CI 7 to 58)
Guzick et al. 1999688932 couples with unexplained infertility (4676 cycles)

Similar baseline characteristics
IUI + FSH (n = 231) versus IUI (n = 234) versus ICI + FSH (n = 234) versus ICI (n = 233)Pregnancy rate/cycle

Live births


Ectopic pregnancy

Multiple pregnancies:
quadruplets, triplets, twins


Cycle cancellation
Significant differences:

Pregnancy rate/cycle:
IUI + FSH: 56/618 (33%)
IUI: 35/717 (18%)
ICI + FSH: 26/637 (19%)
ICI: 14/706 (10%)
OR 3.2 (CI 2.0 to 5.3) (IUI+FSH versus ICI)

Live births:
OR 1.7 (CI 1.2 to 2.6) (IUI+FSH versus IUI)

IUI: 28; IUI+FSH: 41
ICI: 17; ICI+FSH: 31

Ectopic pregnancy:
IUI: 6; IUI+FSH: 22
ICI: 4; ICI+FSH: 5

Multiple pregnancies:
IUI: 2; IUI+FSH: 4
ICI: 0; ICI+FSH: 1





Cycle cancellation:
IUI: 98; ICI: 119
IUI+FSH: 32;
Randomisation using a permuted-block procedure, stratified according to centre

Pregnancy confirmed by hCG levels

Follow-up for 4 cycles
Sengoku et al. 199969497 couples with unexplained infertilityIUI + Conventional FSH (n = 48) versus IUI + low dose, step- up FSH (n = 49)Pregnancy rate/woman

Miscarriage rate

Multiple pregnancy

No significant difference:

Pregnancy rate/woman: RR 1.02 (CI 0.39 to 2.69)

Miscarriage rate: RR 1.0 (CI 0.08 to 13.02)

Multiple pregnancy: RR 2.0 (CI 0.23 to 17.34)

Significant difference in conventional FSH+IUI:

OHSS/woman: RR 3.32 (CI 1.16 to 9.56)
Randomisation by random numbers in sealed opaque envelopes

Pregnancy confirmed by gestational sac on ultrasound

Evaluation of first cycle
Sengoku et al. 199469691 couples with unexplained infertilityIUI + hMG (n = 45; 62 cycles) versus IUI + hMG/GnRHa (n = 46; 69 cycles)Pregnancy rate/cycle

Miscarriage rate

Multiple pregnancy


Cycle cancellation
No significant difference:

Pregnancy rate/cycle:
IUI + hMG: 11.3%
IUI + hMG/GnRHa: 13%
RR 0.87 (CI 0.34 to 2.19)

Miscarriage rate, multiple pregnancy, OHSS/woman not reported

Cycle cancellation: none
Method of randomisation unclear

Pregnancy confirmed by gestational sac on ultrasound

Evaluation of first cycle
Hughes et al. 199869563 women with unexplained infertility (89%), endometriosis (6%), tubal factors (5%)3 low-dose FSH: FSH 2 ampoules versus FSH 4 ampoules versus FSH 6 ampoulesOvulation rate/cycle

Pregnancy rate/cycle


Cycle cancellation

Overall fecundity rate
No significant difference:

Ovulation rate/cycle:
FSH x 2 ampoules: 82%
FSH x 4 ampoules: 81%

FSH x 6 ampoules: 79%

Pregnancy rate/cycle:
FSH x 2 ampoules: 5.4%
FSH x 4 ampoules: 0%
FSH x 6 ampoules: 0%

OHSS/woman: none

Cycle cancellation: none

Overall fecundity rate 1.8%
Computer-generated randomisation via numbered opaque envelopes

Ovulation confirmed by serum progesterone levels 7 days post-hCG
Cantineau et al. 20037013 RCTs (386 participants, 580 cycles)Single IUI versus double IUI (following ovarian stimulation)Pregnancy rate/cycleNo significant difference:

OR 1.45 (CI 0.78 to 2.70)
Patients with different diagnosis of infertility including unexplained infertilitySR1a

From: Evidence tables

Cover of Fertility
Fertility: Assessment and Treatment for People with Fertility Problems.
NICE Clinical Guidelines, No. 11.
National Collaborating Centre for Women's and Children's Health (UK).
London (UK): RCOG Press; 2004 Feb.
Copyright © 2004, National Collaborating Centre for Women’s and Children’s Health.

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