Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
Condition: 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
MeSH terms: Polycystic Ovary Syndrome; Infertility; Endometriosis; Primary Ovarian Insufficiency; Menopause, Premature; Pregnancy, Ectopic; Infertility, Female; Salpingitis
Study type: Interventional
Phase: Phase 1/Phase 2

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)
    

Intervention name(s): Human Chorionic Gonadotropin (hCG); Gonadotropins; GNRH-A Triptorelin; GnRH antagonist
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Administration of hCG (10.000IU) for ovulation triggering; Administration of Menotropin (hMG / FSH and LH at a 1:1 ratio) (150-225IU/day); Administration of Triptorelin (0.1mg/day); Administration of cetrorelix (cetrotide) or ganirelix (orgulatron) (0.25mg/day)
Other intervention name(s): OVITRELLE / PREGNYL; MENOPUR; DECAPEPTYL; CETROTIDE / ORGULATRON
Intervention MeSH terms: Triptorelin Pamoate; Chorionic Gonadotropin; Cetrorelix; Prolactin Release-Inhibiting Factors
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: comparative protocols
Masking: None (Open Label)
Primary purpose: Health Services Research
Keywords: Infertility; Ovarian; Ovulation; IVF; ICSI; Gonadotropin