Brief Title
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
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)
Study Type
Interventional
Primary Outcome
Ovulation Induction
Secondary Outcome
fertilization rate
Condition
Female Infertility
Intervention
Human Chorionic Gonadotropin (hCG)
Study Arms / Comparison Groups
Protocol "A"
Description: Protocol with gonadotropins alone without agonist or antagonist: Gonadotropin treatment begins after spontaneous menses. The gonadotropins (e.g. Menopur, 150-225IU) are injected daily from D2/3 of the cycle (Gonadotropin dose varies based on the follicular response). The moment to trigger ovulation by administration of HCG (e.g. Ovitrelle or Pregnyl, 10.000IU) is determined by monitoring ovulation (folliculogenesis) approximately 14 days after gonadotropins regimen and the presence of at least 3 follicles with 18 mm sizes and at least the levels of E2 reaches 250-300 pg/ml. 36 h after HCG triggering, the mature oocytes are retrieved.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
200
Start Date
February 1, 2018
Completion Date
December 30, 2021
Primary Completion Date
August 22, 2019
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
Gender
Female
Ages
21 Years - 44 Years
Accepts Healthy Volunteers
No
Contacts
Nehman Makdissy, Professor, ,
Location Countries
Lebanon
Location Countries
Lebanon
Administrative Informations
NCT ID
NCT04071574
Organization ID
LU-MC-001/18
Responsible Party
Principal Investigator
Study Sponsor
Lebanese University
Study Sponsor
Nehman Makdissy, Professor, Study Chair, Lebanese University
Verification Date
February 2021