Gonapure® in Multifollicular Stimulation in Egyptian Women Undergoing IVF/ICSI

Study Overview
=================
Brief Summary
-----------------
This study aims to record Efficacy, Safety and tolerability of Gonapure® prescribed for female subjects with infertility Undergoing IVF/ICSI

Detailed Description
-----------------
Gonapure® is a human follicle stimulating hormone (FSH) preparation of recombinant DNA origin and contains no luteinizing hormone (LH) activity. FSH stimulates ovarian follicular growth in women who do not have primary ovarian failure. FSH, the active component of Gonapure® is the primary hormone responsible for follicular recruitment and development. In order to affect final maturation of the follicle and ovulation in the absence of an endogenous LH surge, human chorionic gonadotropin (hCG) must be given following the administration of FSH, when monitoring of the patient indicates that sufficient follicular development has occurred. There is inter-patient variability in response to FSH administration. The dosage and schedule of treatment for female infertility must be determined according to the needs of each patient; it is usual to monitor response by studying the patient's serum oestrogen level and/or by ultrasonic visualization of follicles. Treatment should be started within the first 7 days of the menstrual cycle. Treatment is usually begun with 75 to 450 International units daily by intramuscular injection for 7 to 10 days; followed by individual adjustments according to the patient's follicular response i.e. until an adequate, but not excessive, response is achieved. The investigator will decide the starting dose according to the standard clinical practice (and within the approved label). Treatment is then stopped and followed after 1 or 2 days by a single dose of human chorionic Gonadotropin 10000 International units to induce oocyte maturation.

Official Title
-----------------
An Interventional Study to Assess the Efficacy and Safety of Gonapure® in Multifollicular Stimulation in Egyptian Women Undergoing IVF/ICSI

Conditions
-----------------
Female Infertility

Intervention / Treatment
-----------------
* Drug: Follitropin Alfa


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female subjects aged between 18 and 38 years. Female subjects with body mass index (BMI) ≥ 18 and ≤ 40 kilogram per square meter (kg/m^2) Female subjects with basal FSH less than 10 IU/L and PRL serum values within the normal range in the early follicular phase. Female subjects having both ovaries. Female subjects with normal uterine cavity, which in the investigator's opinion is compatible with pregnancy. Female subjects who have at least 1 wash-out cycle (defined as greater than or equal to 30 days since the last dose of clomiphene citrate or gonadotrophin treatment) since the last ART cycle and/or clomiphene citrate or gonadotrophin treatment prior to starting gonadotropin releasing hormone (GnRH) agonist therapy. Female subjects who are willing and able to comply with the protocol for the duration of the trial Female subjects who have given written informed consent, prior to any trial-related procedure, with the understanding that consent may be withdrawn by the subject at any time without prejudice to her future medical care. Exclusion Criteria: Female subjects with any medical condition, which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of the drug. Female subjects with uterine myoma requiring treatment. Female subjects with any contraindication of being pregnant and/or carrying a pregnancy to term. Female subjects with history of tumors of the hypothalamus and pituitary gland. Female subjects with history of ovarian, uterine or mammary cancer. Female subjects with history of hypersensitivity to the active substance follitropin alpha, FSH, or to any of the excipients of Gonapure ®. Female subjects with untreated hydrosalpinx diagnosed by U/S. Female subjects with abnormal gynecological bleeding of unknown etiology. Female subjects with any medical condition which, in the opinion of the investigator, would prevent an effective response, such as primary ovarian failure, or malformations of the reproductive organs incompatible with pregnancy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 38 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Follitropin Alfa (Gonapure) | Drug: Follitropin Alfa<br>* Patients must be prescribed Follitropin Alfa (Gonapure®)<br>* Other names: Gonapure ®;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of oocytes retrieved on the day of Ovum Pick-Up |  | 50 days after baseline visit (EOS) | 
| Number of Mature Oocytes (MII) Retrieved Per Participant | Metaphase II (MII): The oocyte is in the second phase of meiosis and is mature. Oocytes at this stage of maturity are ready for fertilization. Mean number of Mature oocytes (MII) retrieved on the day of ovum pick up (OPU) will be calculated. Oocyte retrieval is a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. | 50 days after baseline visit (EOS) | 
| Quality of Oocytes Retrieved per participant | It is graded on a good-fair-poor scale: Good Clear cytoplasm/normal shape Single distinct polar body Clear/thin zona pellucida Fair Slightly grainy cytoplasm/misshapen Fragmented/abnormal polar body Slightly pigmented/amorphous zona Cytoplasmic bodies PV (vitelline platelets) debris Poor Dark/grainy cytoplasm/misshapen >1 polar body structure Pigmented/thickened zona Vacuoles PV (vitelline platelets) debris Good Quality embryos per participant. Those embryos that have reached the most advanced developmental stage and have the least cellular fragmentation (Grades A and/or B) will be considered Good Quality embryos and will be selected for transfer. Number of transferred embryos per participant. Percentage of Participants with Clinical Pregnancy. Clinical pregnancy is defined by the number of sacs and hearts with activity per ultrasound scan. | 50 days after baseline visit (EOS) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eventual AE/SAEs related to the administration of Gonapure® |  | 50 days after baseline visit (EOS) | 
| Total & Mean Gonapure ® Daily Dose | Time Frame: Start of treatment until end of stimulation cycle | 14 days | 
| Number of follicles ≥ 18 mm on day of administration of hCG |  | 50 days after baseline visit (EOS) | 
| Number of Participants with Multiple Pregnancies | Multiple pregnancies were defined as 2 or more fetal hearts with activity. | 50 days after baseline visit (EOS) | 
| Number of Participants with Ovarian Hyperstimulation Syndrome | OHSS is a syndrome which can manifest with enlarged ovaries, advanced ascites with increased vascular permeability, pleural fluid Accumulation, hemoconcentration, and increased blood clotting. | 50 days after baseline visit (EOS) |