FSH Followed by HMG vs FSH Plus HMG in IVF

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to compare the clinical outcomes of sequential administration of FSH and HP-hMG FSH alone versus concomitant administration of FSH and HP-hMG during controlled ovarian stimulation in IVF cycles.

Detailed Description
-----------------
Women who are planned to be subjected to IVF/ICSI through COS by long GnRHa protocol will be assessed for possibility of participation in our study. Eligible participants in our study will be those with regular menstrual cycle (21-35 days) and normal uterine anatomy (confirmed by transvaginal ultrasound examination and in some cases hysteronsalpingography and hysteroscopy). Women with any of the following criteria will be excluded from the study: 1) age < 20 or > 37 years; 2) body mass index (BMI) < 18 or > 25 kg/m2; 3) low ovarian reserve (AFC < 7 and/or AMH < 1.1 ng/ml); 4) presence of polycystic ovarian syndrome (PCOS), endometrioma or hydrosalpinx; 5) history of chemotherapy, radiotherapy or ovarian surgery; 6) the husband needs testicular biopsy to obtain sperm; or 7) previous implantation failure. A written informed consent will be taken from each women selected to participate before inclusion in the study. All women participating in the study will start GnRHa on day 21 of the preceding cycle and when down regulation occurs each woman will be randomly allocated into one of the two groups; group 1 and group 2. Women in group 1 will receive 225 IU FSH alone from day one of ovarian stimulation and when the follicular diameters reaches 10-12 mm, the 150 IU HP-hMG will substitute FSH and continued to the day of triggering. Women in group 2 will receive 150 IU FSH plus 75 IU HP-hMG from day one of ovarian stimulation and 150IU HP-HMG when the follicular diameters reaches 10-12 mm till day of triggering. The randomization will be simple and balanced (1:1) and will be carried out by a nurse through sealed, unlabeled, opaque envelopes containing computer-generated random numbers. The data assesor will be blinded to group assignment. In both groups, estradiol and LH will be measured on the third day of menstruation before start of stimulation and on day 6 of stimulation TVS will be performed. Progesterone and E2 will be measured and on day of triggering. The primary outcome measure of this study will be the ongoing pregnancy rate. The secondary outcomes measures will be cancellation rate, the number of oocytes retrieved, the number of embryos, the number of vitrified embryos, the clinical pregnancy rate, the implantation rate, OHSS rate, multiple pregnancy rate, and the miscarriage rate.

Official Title
-----------------
Follicle Stimulating Hormone (FSH) Followed by Human Menopausal Gonadotropin (HMG) Versus FSH Plus HMG During Controlled Ovarian Stimulation for in Vitro Fertilization

Conditions
-----------------
IVF

Intervention / Treatment
-----------------
* Drug: FSH
* Drug: HP-hMG


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Women who are planned to be subjected to IVF/ICSI through COS by long GnRHa protocol. Women with regular menstrual cycle (21-35 days) and normal uterine anatomy (confirmed by transvaginal ultrasound examination and in some cases hysteronsalpingography and hysteroscopy). Exclusion Criteria: Age < 20 or > 37 years. Body mass index (BMI) < 18 or > 30 kg/m2. Low ovarian reserve (AFC < 7 and/or AMH < 1.1 ng/ml). Presence of polycystic ovarian syndrome (PCOS). Endometrioma or hydrosalpinx. History of chemotherapy, radiotherapy or ovarian surgery. The husband needs testicular biopsy to obtain sperm. Previous implantation failure.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 37 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FSH then HP-hMG<br>Women will receive 225 IU FSH alone from day one of ovarian stimulation and when the follicular diameters reaches 10-12 mm, the 150 IU HP-hMG will substitute FSH and continued to the day of triggering | Drug: FSH<br>* Controlled ovarian stimulation by FSH followed by HMG versus FSH plus HMG<br>* Other names: Fostimon, Gonal-F, Puragon;Drug: HP-hMG<br>* Controlled ovarian stimulation by FSH followed by HMG versus FSH plus HMG<br>* Other names: Meriofert, Menopure;|
| Active Comparator: FSH + HP-hMG<br>Women will receive 150 IU FSH plus 75IU HP-hMG from day one of ovarian stimulation and when the follicular diameters reaches 10-12 mm 150 IU HP-HMG till day of triggering | Drug: FSH<br>* Controlled ovarian stimulation by FSH followed by HMG versus FSH plus HMG<br>* Other names: Fostimon, Gonal-F, Puragon;Drug: HP-hMG<br>* Controlled ovarian stimulation by FSH followed by HMG versus FSH plus HMG<br>* Other names: Meriofert, Menopure;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy rate | Number of ongoing pregnancies (defined as pregnancies passed beyond 12 weeks gestational age) divided by the number of women randomized | 12 weeks gestational age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | Number of clinical pregnancies (defined as presence of at least one intrauterine gestational sac with fetal pole and cardiac activity on TVS scan at 4-6 weeks after the ET) divided by the number of women randomized | 6 weeks after embryo transfer | 
| Implantation rate | Number of gestational sacs on TVS scan at 4-6 weeks after ET divided by the number of transferred embryos | 6 weeks after embryo transfer | 
| Miscarriage rate | Number of first trimester miscarriages (before 12 weeks gestational age) divided by the number of clinical pregnancies | 12 weeks gestational age | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ovarian stimulation, subfertility, FSH, HMG