Clinical trial NCT04071574: Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
Official title: Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Women With Infertility Problems
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Female Infertility
Female Infertility Due to Ovulatory Disorder
Premature Ovarian Failure
Polycystic Ovary Syndrome
Female Infertility of Tubal Origin
Ectopic Pregnancy
Salpingitis
Female Infertility Due to Tubal Block
Female Infertility Due to Tubal Occlusion
Hydrosalpinx
Female Infertility - Cervical/Vaginal
Female Infertility Endocrine
Endometriosis
Fibroids
Congenital Uterine Anomaly
Infections Uterine
Female Infertility of Other Origin
Keywords: Infertility; Ovarian; Ovulation; IVF; ICSI; Gonadotropin
Lead sponsor: Lebanese University
Sponsor class: OTHER
First posted: 2019-08-28
Enrollment: 200
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 44
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: comparative protocols
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The study will describe the effectiveness of ovarian stimulation in correlation with female infertility causes in a Lebanese population: a comparative study using 5 protocols of ovulation induction (treatment with "A" gonadotropins alone, "B" short GnRH agonist, "C" multiple-dose GnRH antagonist, "D" long GnRH agonist and "E" combined protocol of GnRH antagonist and agonist) and the outcomes of ICSI. This comparative study will help clinicians to select the relevant protocol of ovarian stimulation related to the female infertility disorders.

Detailed description: One in six couples worldwide is affected by infertility, which defined as the inability to conceive after one year or more of regular and unprotected intercourse. It has been stated that 48.5 million couples in the world, with unprotected coitus, suffer from infertility. In about 50% of them, the infertility is due to female factors and diseases associated with the female reproductive system. Epidemiological studies show that 10 to 15% of all married couples are estimated to have infertility problems in the Middle East. Lebanon, in particular, is characterized with traditional and westernized lifestyles; It has high rates of smoking and caffeine intake, pollution and high rates of consanguinity marriage (11 to 17%), which affect considerably the conception rate.

The desire to procreate is naturally present in women all over the world. Due to various advances in medical procreation techniques, it has become possible for many women to realize their hope. Women were more likely to be psychologically distressed to infertility and suffer from poor quality of life more than men once they are diagnosed as infertile.

The causes of female infertility can have a genetic, anatomical or physiological origin. Among the most common genetic causes of female infertility are the chromosomes abnormalities: the numbers of X chromosomes, homogeneous or mosaic; other abnormalities are reciprocal translocations, Robertsonian translocations, inversions, supernumerary markers or abnormalities of the X chromosome structure. In such cases, no treatment and procreation require an egg donation. But the main causes of female infertility are physiological and anatomical, such as ovulatory disorders (25%), endometriosis (15%), pelvic adhesions (12%), tubal blockage (11%), other tubal abnormalities (11%), hyperprolactinemia (7%) and some minor causes. In addition, leiomyomas, fibroma, polyps, and tubal disease, may reduce fertility. In addition came the environmental factors (drugs, pesticides, food, tobacco ...) and there is an increase in the percentage of infertile women with advancing female age. A French national survey on lifestyles and toxic factors in infertile couples showed that in women, tobacco generates a risk twice as high as being infertile, a decrease in the ovarian reserve where the level of anti-Mullerian hormone (AMH) decreases, irregular short cycles and dysmenorrhea are also found in smokers. In addition, products contained in tobacco such as cotinine, cadmium and hydrogen peroxide are found in the follicular fluid and would be responsible for an alteration of the recovery of oocyte meiosis.

Couples who have problems with conception are referred to a medically assisted procreation (MAP) for fertility treatments. These treatments can be very stressful both psychologically and physically. Indeed, the numerous medical appointments and examinations, as well as the many bereavements and failures, experienced following repeated attempts at conception can to consume the married, social and professional life of couples. In addition, fertility issues require significant financial resources to cover the costs of fertility treatments, but also those related to the maternal and fetal complications of pregnancy, which are more frequent in the case of MAP pregnancies than in spontaneous conception.

Control of the ovarian stimulation is the key component of assisted reproductive technologies (ART) that have shifted the clinical practice of natural mono-follicular cycles into multi-follicular stimulated cycles. The increase in the number of follicles, and consequently the number of oocytes recovered, improved pregnancy rates in women undergoing In Vitro Fertilization (IVF) / Intra-Cytoplasmic Sperm Injection (ICSI), not only by increasing the number of available embryos but also by allowing embryo culture extended and allowing the selection of higher quality embryos to be transferred. However, several studies have addressed the issue of the optimal number of oocytes recovered following controlled ovarian stimulation (COS) for IVF / ICSI and demonstrated that the ovarian response is independently related to Live Birth Rate (LBR) after IVF / ICSI.

Many new treatment modalities for ovarian stimulation have been introduced over the years - often with insufficient evidence of safety and efficacy - using different compounds and regimens for ovarian stimulation, triggering oocyte maturation, interventions preceding stimulation supplementation phase. The most important clinical challenge is to find the right balance between improving the chances of success (birth of a healthy child), a reasonable cost, acceptable discomfort for the patient, and a minimal complication rate. New developments make ovarian stimulation less intense and more individualized. The choice of the ovarian stimulation protocol is one of the most important steps in IVF/ICSI treatment.

This study aims to identify and evaluate ovarian stimulation protocols applied to different patients with different causes of female infertility prior to medically assisted procreation techniques in order to know if there is a relationship between a given protocol and the result obtained for each class of infertility. Therefore, 360 ICSI in 200-300 couples will be studied in order to evaluate the link between ovarian stimulation protocols and outcomes of ICSI.

The population will be divided into 3 groups:

1. Group "OD" for ovulation disorders caused by endocrine disorders such as the polycystic ovarian syndrome (PCOS) and/or premature ovarian failure (POF)
2. Group "TD" for tubal disorders caused by previous ectopic pregnancy, salpingectomy, tubal obstruction and/or hydrosalpinx
3. Group "UCD" for uterine and cervical disorders caused by fibroids, endometriosis, infection and/or congenital uterine anomaly (CUA)

Eligibility criteria: Inclusion Criteria:

* must not show any of the excluded criteria
* Patients affected by female infertility due to particularly Ovulatory Disorder, Premature Ovarian Failure, Polycystic Ovary Syndrome, Tubal Origin, Ectopic Pregnancy, Salpingitis, Tubal Block/Occlusion, Hydrosalpinx, Cervical/Vaginal, Endocrine, Endometriosis, Fibroids, Congenital Uterine Anomaly, Infections Uterine, and Female Infertility of Other Origin
* The selection of subjects' age must be group matched between protocols of treatment. Premature ovarian failure is defined as AMH (Anti Mullerian Hormone) ≤ 2 ng/mL.
* Willing to collaborate and to attend to the clinical follow-ups for the next three years
* Patients willing to sign informed consent
* Able and willing to comply with all study requirements
* Absence of genetic causes
* Medically suitable to undergo ovarian stimulation
* Normal serum chemistry and hematology screening tests
* Negative human immunodeficiency virus (HIV), hepatitis B (HBV), hepatitis C (HCV) serology
* No history of malignancy
* Complete history \& physical examination

Exclusion Criteria:

* Subjects to be excluded from the study if the male (husband) had any male infertility problem(s)
* Patients with any genetic abnormalities
* Patients with histories of neurologic conditions including moderate or severe head injury, stroke, cerebral or bone damage or malignancies, brain abnormalities, learning disability, major medical or psychiatric illness, and metabolic/cardiovascular disease or evidence of cardiac/renal damage or malignancies, alcohol, loss of weight during the last 2 years, chemotherapy or immunosuppressive therapy.
* Women aged 45 years and older, under 21 years

Primary outcomes:
measure: Ovulation Induction
timeFrame: 36 hours
Secondary outcomes:
measure: fertilization rate
timeFrame: 12 months
measure: embryo quality
timeFrame: 12 months
measure: pregnancy rate
timeFrame: 12 months
measure: live birth rate
timeFrame: 12 months
Other outcomes:
Locations:
city: Tripoli
country: Lebanon
facility: Lebanese University, faculty of sciences III
state: North Lebanon
Study officials:
affiliation: Lebanese University
name: Nehman Makdissy, Professor
role: STUDY_CHAIR
affiliation: Lebanese University
name: Samar El Hamoui, Dr
role: STUDY_DIRECTOR
References: