Clinical trial NCT02461173: Stimulated Intrauterine Insemination Cycles and Unstimulated Intrauterine Insemination Cycles in Couples With Unexplained Infertility
Official title: Comparison Between Stimulated Intrauterine Insemination Cycles and Unstimulated Intrauterine Insemination Cycles in Couples With Unexplained Infertility
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Infertility
Lead sponsor: Cairo University
Sponsor class: OTHER
First posted: 2015-06-03
Enrollment: 450
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Four hundred and fifty women with unexplained infertility will be divided into 3 equal groups using computer generated random numbers: Group 1 will have up to 4 stimulated IUI cycles, group 2 will have up to 4 unstimulated cycles, women who do not become pregnant after the 4 cycles in groups 1 and 2 will be advised to have regular intercourse at the expected time of ovulation. Group 3 will be the control group will be advised to have regular sexual intercourse at the time of ovulation for 6 months

Detailed description: Unexplained infertility is a common diagnosis encountered in the subfertility clinic; about 15-30% of infertile couples will be diagnosed as having unexplained infertility. Couples are usually diagnosed as having unexplained infertility if the woman has ovulatory cycles, patent tubes and the spouse has a normal semen analysis according to the world health organisation criteria.

In the absence of an organic abnormality or a clear functional defect, couples with unexplained infertility have been subjected to several empirical treatments including intra-uterine insemination (IUI). The application of ovarian stimulation in IUI is advocated, even if the woman has ovulatory cycles, to improve the pregnancy rates with IUI. However, the application of ovarian stimulation has two main drawbacks: The increased chances of a multiple pregnancy and ovarian hyperstimulation syndrome. To avoid these complications unstimulated IUI cycles have been investigated. The objective of the study is to evaluate the role of stimulated and unstimulated IUI cycles in the management of unexplained infertility.

The study will be conducted in Cairo university hospitals and BeniSuef University hospitals All patients with unexplained infertility attending both sites will be invited to participate in the study. The study will be explained and only couples who sign written consents will be included in the study.

Four hundred and fifty women with unexplained infertility will be divided into 3 equal groups using computer generated random numbers: Group 1 will have up to 4 stimulated IUI cycles, group 2 will have up to 4 unstimulated cycles, women who do not become pregnant after the 4 cycles in groups 1 and 2 will be advised to have regular intercourse at the expected time of ovulation. Group 3 will be the control group will be advised to have regular sexual intercourse at the time of ovulation for 6 months On the 3rd day of menstruation group 1 will have a vaginal ultrasound and will receive daily intramuscular 150 IU of human menopausal gonadotropins (hMG, Merional ®, IBSA, Lugano, Switzerland) starting from the 3nd day of menstruation. On day 8 the ultrasound will be repeated and serum E2 will be measured, hMG dose will be adjusted and continued and the frequency of ultrasound scans will be individualized. HMG will be stopped when at least 2 follicles measuring 18 mm are associated with serum E2 of 500-3000 Pg/mL, this was followed by the administration of 10000 IU of human chorionic gonadotropin (hCG; Choriomon®, IBSA) Women in group 2 will be asked to test their morning urine specimen for luteinizing hormone daily starting 4 days before the expected day of ovulation. This will be done using a qualitative kit. Intrauterine insemination will be performed on the day after the surge in urinary excretion of luteinizing hormone.

Women in group 3 will be asked to test their urine for luteinizing hormone by the same method as group 2. They will be asked to have an intercourse on the day after the surge in urinary excretion of luteinizing hormone and this will be repeated for 12 months.

Semen specimens for groups 1 and 2 will be evaluated and prepared for IUI within one hour after collection. Semen will be diluted 1:2 (vol/vol) with HEPES-buffered Ham's F10 medium containing 1.5 percent serum albumin. After centrifugation for 10 minutes, the pellets will be resuspended and combined in 3 ml of the medium.

The sperm suspension will be centrifuged for 10 minutes, and the pellet was resuspended in 0.35 ml of medium. Approximately 0.05 ml will be used to determine the concentration and motility of sperms. The remaining sample will be drawn into a shepherd catheter attached to a 1 mL syringe and injected into the uterus.

The procedure will be repeated for up to 4 months in groups 1 and 2, if pregnancy does not occur. Women who do not conceive after the 4 trials will be asked to check their urine for luteinizing hormone using the ovulation detection kits and have an intercourse on the day following the luteinizing hormone surge. This will be repeated for 8 months.

The pregnancy rates of the 3 groups will be compared after the 4 months and after one year.

Eligibility criteria: Inclusion Criteria:

* Unexplained infertility

Exclusion Criteria:

* Known allergy to FSH
* Diabetes, hypertension, known cardiac, renal or liver disease.

Primary outcomes:
measure: Number of participants with ongoing pregnancy
timeFrame: 12 weeks after IUI or timed sexual intercourse
Secondary outcomes:
Other outcomes:
Locations:
city: BeniSuef
country: Egypt
facility: BeniSuef University hospitals
city: Cairo
country: Egypt
facility: Cairo university hospitals
Study officials:
References:
citation: Brandes M, Hamilton CJ, van der Steen JO, de Bruin JP, Bots RS, Nelen WL, Kremer JA. Unexplained infertility: overall ongoing pregnancy rate and mode of conception. Hum Reprod. 2011 Feb;26(2):360-8. doi: 10.1093/humrep/deq349. Epub 2010 Dec 16.
citation: Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, Haugen TB, Kruger T, Wang C, Mbizvo MT, Vogelsong KM. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010 May-Jun;16(3):231-45. doi: 10.1093/humupd/dmp048. Epub 2009 Nov 24.
citation: Quintero RB, Urban R, Lathi RB, Westphal LM, Dahan MH. A comparison of letrozole to gonadotropins for ovulation induction, in subjects who failed to conceive with clomiphene citrate. Fertil Steril. 2007 Oct;88(4):879-85. doi: 10.1016/j.fertnstert.2006.11.166.