Clinical trial NCT03876145: The Four Methods of Ovarian Stimulation in Patients With Polycystic Ovarian Syndrome
Official title: A Comparison of Four Methods of Ovarian Stimulation With GnRH Antagonist in Patients With Polycystic Ovarian Syndrome in Royan Institute; A Randomized Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Polycystic Ovary Syndrome
Ovarian Hyperstimulation Syndrome
Lead sponsor: Royan Institute
Sponsor class: OTHER_GOV
First posted: 2019-03-15
Enrollment: 120
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a randomized controlled clinical trial to compare the pregnancy outcomes of mild and minimal stimulation in infertile women with polycystic ovarian syndrome. The study population consisted of all infertile women with polycystic ovary syndrome based on Rotterdam criteria who have not succeed to achieve fertility despite multiple treatments such as drug therapy, laparoscopic surgery, and the frequent failure of induction therapy using gonadotropins and are now candidate for in vitro fertilization (IVF) or intra cytoplasmic sperm injection (ICSI) in Reproductive Biomedicine Research Center, Royan institute, Tehran Iran.

Detailed description: An overview of the history of assisted reproductive technologies such as IVF and ICSI that are based on the process of ovulation stimulation, suggests that although this process was initially welcomed with the aim of achieving a large number of oocytes and embryos, consequences such as low quality of obtained oocytes and embryos, failure in achieving the desired results in fertility of treated patients, and the incidence of adverse effects such as ovarian hyper stimulation syndrome have made researchers re-examine the process of ovulation stimulation. Hence, mild ovulation stimulation method has been introduced to the field of assisted reproductive techniques (ART) in recent years. This method includes the prescription of low doses of gonadotropins or shorter duration of its administration in the ovulation stimulation cycle. Mild ovulation method has advantages such as reduction of the physical, mental, and financial risks of treatment which can improve the quality assisted reproductive services provided for infertile couples.

Several studies have confirmed the efficiency of this method of ovulation stimulation as a way for improving the quality of the ovulation process and achieving desirable results in fertility. However, the important and interesting point in studies conducted in this area, particularly on IVF and ICSI cycles, is that the application of this method has been mostly investigated in normal populations and, after the approval of its efficiency, it has been recommended to be used in patients with poor or high ovarian response. It should be also mentioned that efficiency of this method in patients with poor ovarian response has been evaluated in a few studies, while in patients with high ovarian response such as those suffering from polycystic ovary syndrome, only few studies have been conducted in patients with a history of ovarian hyper stimulation syndrome. On the other hand, in many cases, the efficiency of mild ovulation stimulation, in which lower doses or shorter durations of gonadotropin administration are desired, has been investigated, and the application of minimal ovulation stimulation method, in which the use of clomiphene citrate is also included besides lower doses or shorter durations of gonadotropin administration, has been studied in a few cases.

In addition to the dose and duration of gonadotropin administration, another important point in achieving the desired results of treatment using the ovulation stimulation cycles is the type of gonadotropin. The studies conducted on the comparison of recombinant-FSH (rec-FSH) and Human Menopausal Gonadotropin (HMG) types of gonadotropin indicate the superiority of HMG gonadotropins, as the results show that the administration of HMG gonadotropins will lead to achieving fewer but high quality oocytes and embryos. By contrast, rec-FSH application puts the patients at increased risk of ovarian hyper stimulation syndrome. However, the interesting and important point in most of these studies is that this comparison has been drawn in long-term treatment cycles, while few studies have been conducted on antagonist treatment cycles which do not fully corroborate the results obtained from long-term cycles.

According to what mentioned above, the present research aims to study the efficiency of minimal ovulation stimulation method in the treatment of infertile patients with poly cystic ovarian syndrome (PCOS) and also the effect of gonadotropin type on treatment cycles with antagonist gonadotropin-releasing hormone (GnRH). It is hoped that the findings of the present research provide solutions for improving the quality of infertility treatment in PCOS patients, who currently undergo IVF or ICSI as a last resort.

Eligibility criteria: Inclusion Criteria:

1. Infertile women with polycystic ovary syndrome based on Rotterdam criterion
2. 20\<Age\<38
3. BMI\<30
4. Non recurrent miscarriage
5. Non endocrine, hematologic and autoimmune disorders
6. Non chromosomal and genetic abnormalities
7. Non uterine anomalies, surgical history, endometriosis, adenomyosis, hydrosalpinx, uterine fibroids
8. Non azoospermia

Exclusion Criteria:

1. Patient's tendency for withdrawal

Primary outcomes:
measure: Fertilization rate
timeFrame: 16-18 hours after start of IVF or ICSI, which occurs on day of oocyte pick-up (34-36 hours after hCG administration [approximately Stimulation Day 10]).
measure: Implantation rate
timeFrame: 4 weeks after embryo transfer
measure: Clinical pregnancy rate
timeFrame: 4 weeks after embryo transfer
Secondary outcomes:
measure: ovarian hyper stimulation syndrome (OHSS) rate
timeFrame: Up to approximately 2 month after oocyte pick-up (34-36 hours after hCG administration [approximately Stimulation Day 10]).
measure: Total number of retrieved oocytes
timeFrame: Day of oocyte pick-up, 34-36 hours after human curionic gonadotropin (hCG) administration (approximately Stimulation Day 10).
measure: Quality of retrieved oocytes
timeFrame: Day of oocyte pick-up, 34-36 hours after hCG administration (approximately Stimulation Day 10).
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Royan Institute
Study officials:
affiliation: Department of Endocrinology and Female Infertility, ACECR, Tehran, Iran.
name: Firoozeh Ghaffari, M.D.
role: STUDY_DIRECTOR
affiliation: Department of Endocrinology and Female Infertility, ACECR, Tehran, Iran.
name: Azar Yahyaei, M.Sc.
role: PRINCIPAL_INVESTIGATOR
References: