Dual FSH/HCG Trigger in Letrozole Stimulated Intrauterine Insemination Cycles in Women With Unexplained Infertility

Study Overview
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Brief Summary
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The objective of this study was to evaluate the outcome of follicle stimulating hormone (FSH) co-administration with human chorionic gonadotrophins trigger for women with unexplained infertility (UEI) and assigned for letrozole (LTZ) stimulated intrauterine insemination (IUI) cycles .

Detailed Description
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This prospective randomized controlled study included 108 women with unexplained infertility recruited among those attending the Gynecology Outpatient Clinics of, Benha University Hospital, and private settings, Alkalubia, Egypt from Jun 2013 to Aug 2015. The study protocol was approved by the Local Ethics Committee and written informed consents were taken from both partners before starting of the study. All women received the same regimen of ovarian stimulation using Letrozole (Femara; Novartis pharma AG, Basle, Switzerland) 2.5 mg tab twice daily for 5 days starting from cycle day 3. Transvaginal ultrasound scan (TVS) was performed daily from cycle day 9 and a total of 10,000 IU of hCG (Epifasi, EPICO) was administered to those in whom at least one ovarian follicle was ≥18 mm in size. On the day of hCG administration women were randomly categorized into two groups according to a computer generated random numerical table. Envelopes containing the allocation information were chosen sequentially by patient herself in presence of her husband. Group A received FSH (urofollitropin; Fostimon, IBSA, Bazel, Swiz; 75 IU amp) 150 IU injected once on day of hCG injection and group B received no FSH on day of hCG injection. Intrauterine insemination was performed 36 hours after HCG injection. Women in both groups received luteal phase support in the form of vaginal progesterone, (Prontogest 400 mg Vaginal Pessaries, IBSA) twice a day, starting from the day after IUI and continued till the eighth week, if the pregnancy test was positive.Two weeks later, quantitative ßhCG was estimated to diagnose chemical pregnancy. However, TVS was performed 4 weeks after positive pregnancy test to confirm clinical pregnancy by the presence of gestational sac with fetal echoes and pulsation and to exclude ectopic pregnancy. All women enrolled in the study underwent the study protocol for three consecutive cycles unless got pregnant.

Official Title
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Concomitant Administration of Follicle-stimulating Hormone at the Time of Human Chorionic Gonadotropin Trigger in Letrozole Stimulated Intrauterine Insemination Cycles in Women With Unexplained Infertility

Conditions
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Unexplained Infertility

Intervention / Treatment
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* Drug: Human chorionic gonadotropin
* Drug: FSH co-trigger
* Drug: Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unexplained infertility for more than 2 years Normal ovulation proved by midluteal serum progesterone level >5 ng/ml, Patent fallopian tubes confirmed by hysterosalpingography or laparoscopy Normal semen analysis according to the modified World Health Organization (WHO) criteria Normal hormonal profile (FSH, LH, prolactin and TSH) in the early follicular phase. Exclusion Criteria: Other causes of infertility ( tubal factors, polycystic ovary syndrome (PCOS), endometriosis) Ovarian cysts, FSH >10 mIU/ml. Previous intrauterine insemination (IUI )cycles, Liver or kidney diseases, Hypersensitivity to the used medications.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>In letrozole stimulated cycle: On the day of ovulation trigger the patient received standard dose of Human chorionic gonadotropin (10,000 IU). | Drug: Human chorionic gonadotropin<br>* In letrozole stimulated cycle; Human chorionic gonadotropin ( hCG) 10000 IU was given intramuscular when the mean ovarian follicle diameter was ≥18 mm.<br>Drug: Letrozole<br>* Letrozole oral tablets (Femara 2.5 mg tablet; Novartis Pharma Services, Switzerland) 2.5 mg tab twice daily for 5 days from cycle day 3.<br>|
| Experimental: Study<br>In letrozole stimulated cycle: On the day of ovulation trigger the patient received hCG 10000 IU plus FSH co-trigger (urofollitropin; Fostimon, IBSA, Bazel, Swiz; 75 IU amp) 150 IU injected once . | Drug: Human chorionic gonadotropin<br>* In letrozole stimulated cycle; Human chorionic gonadotropin ( hCG) 10000 IU was given intramuscular when the mean ovarian follicle diameter was ≥18 mm.<br>Drug: FSH co-trigger<br>* In letrozole stimulated cycle; FSH (urofollitropin; Fostimon, IBSA, Bazel, Swiz; 75 IU amp) 150 IU injected once intramuscular when the mean ovarian follicle diameter was ≥18 mm.<br>Drug: Letrozole<br>* Letrozole oral tablets (Femara 2.5 mg tablet; Novartis Pharma Services, Switzerland) 2.5 mg tab twice daily for 5 days from cycle day 3.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate per cycle (PR/C) and per woman (PP/W) | Achievement of clinical pregnancy defined as the presence of an intrauterine gestational sac with a pulsating fetal heart beat on ultrasound | Throughout the study completion; up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of ovarian hyperstimulation syndrome (OHSS) | Number of participants developed ovarian hyperstimulation syndrome (OHSS) per all women received intervention | Throughout the study completion; up to 3 months | 
| Multiple pregnancies | Number of participants had multiple pregnancy per women achieved pregnancy . | Throughout the study completion; up to 3 months | 
| The live birth rate per woman (LB/W). | Number of live birth per women receiving intervention. | Throughout the study completion; up to 2 year |