Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05143723 |
| Other study ID # |
04081990 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
January 20, 2020 |
| Est. completion date |
June 10, 2022 |
Study information
| Verified date |
November 2021 |
| Source |
Kuban State Medical University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Purpose: To determine the efficacy and safety of daily injections of gonadotropin-releasing
hormone agonist in comparison with the standard strategy of supporting the luteal phase in
protocols with gonadotropin-releasing hormone antagonists, in patients at risk of developing
ovarian hyperstimulation syndrome and changing the trigger to a gonadotropin-releasing
hormone agonist.
Materials and Methods: This prospective, controlled, randomized study, conducted at the
Clinic of the Federal State Budgetary Educational Institution of Higher Education of the
KubSMU of the Ministry of Health of Russia, included 102 patients at risk of developing
ovarian hyperstimulation syndrome, who were on protocols with gonadotropin-releasing hormone
antagonists and changing the ovulation trigger to a gonadotropin-releasing hormone agonist.
All patients underwent blastocyst transfer on day 5. Patients of the first group (n = 51)
received as support for the luteal phase gonadotropin-releasing hormone agonist daily 0.2 mg,
subdermally, patients of the second group (n = 51) progesterone 10 mg 3 times a day, orally
and estradiol 1 mg 3 times a day, transdermal. The level of progesterone on the day of
transfer, the incidence of clinical pregnancy, and the incidence of ovarian hyperstimulation
syndrome in both groups were compared.
Description:
This prospective randomized study was conducted at the Clinic of the Federal State Budgetary
Educational Institution of Higher Education of the Kuban State Medical University of the
Ministry of Health of Russia from January 2020 till April 2021 and was approved by the
ethical committee of the FSBEI HE KubSMU of the Ministry of Health of Russia Protocol No. 83
dated 07.11.2019. It included 102 patients at risk of developing OHSS, all of whom gave
written informed voluntary consent. Inclusion criteria were: age - from 20 to 40; AMH - more
than 2.5 ng/ml; the number of antral follicles (AFC) - more than 15 (menstrual cycle days
1-5); stimulation of ovarian function in the protocol with GnRH-antagonist in IVF/ICSI
cycles, with the change of the ovulation trigger to GnRH-a; tubal, unspecified and
anovulatory infertility; body mass index (BMI) from 18 to 29 (inclusive); 15 or more
follicles per day of ovulation trigger injection.
Exclusion criteria: presence of external genital endometriosis; male factor of infertility;
hydrosalpinx and/or tubo-ovarian formation (on one or both sides) according to
hysterosalpingography and/or ultrasound investigation; malformations of internal genital
organs, including conditions after surgical correction of malformations of internal genital
organs; acquired deformities of the uterine cavity, in which embryo implantation or pregnancy
is impossible; contraindications to the IVF/ICSI program; severe systemic diseases; cycles
with cryopreserved sperm or oocytes; oocyte donation. The patients were divided into two
groups using the envelope method. On days 2-5 of the menstrual cycle, a study of the level of
blood hormones was carried out: follicle-stimulating hormone (FSH), luteinizing hormone (LH),
progesterone, and estradiol, as well as transvaginal ultrasonography of the pelvic organs to
determine the number of antral follicles (AFC) and exclusion of contraindications for the
start of COS. Then СOS was carried out using gonadotropins, menotropins. The standard daily
starting dose of stimulant drugs was determined according to age, BMI, original FSH, AFC, and
ovarian response in women undergoing previous IVF/ICSI cycles. The ovarian response was
assessed using folliculometry, starting from 5-6 days of COS, when two follicles with an
average diameter of more than 14 mm or one more than 16 mm were reached, GnRH-ant was
prescribed at a dose of 0.25 mg daily. Ovulation trigger (GnRH-a) was introduced on condition
that two or more follicles with a diameter of 17-18 mm were reached; after 36 hours,
transvaginal ovarian puncture (TVOP) was performed under ultrasound control. All mature eggs
(ova) were fertilized using IVF or ICSI methods. Fertilization was assessed after about 20
hours, and the embryos were transferred into the uterine cavity on day 3 or 5. LPS in all
patients started the day after oocyte retrieval and continued until 8 weeks of gestation in
case of positive result.
Patients of the first group (n=51) received GNRH-a for LPS at a dose of 0.2 mg, subdermally,
daily from the second day after TVOP. The second group of patients (n=51) received
progesterone as LPS at a dosage of 30 mg per day, per os, and estradiol at a dosage of 3 mg
per day, transdermally starting from the second day after TVOP till 8 weeks of pregnancy. The
embryo transfer was carried out 3-5 days after TVOP, one or two embryos were transferred,
depending on the morphological assessment of the embryo. On the day of transfer, a study of
the level of progesterone in the peripheral blood was carried out. Pregnancy testing was
performed by determining the level of β-hCG in the peripheral blood 14 days after the embryo
transfer. Data were collected on participant characteristics, COS, and embryology.
Characteristics included: patient's age, characteristics of ovarian reserve (AMH, FSH), type,
duration and cause of infertility, duration of COS, the total dose of gonadotropin treatment,
endometrial thickness on the day of ovulation trigger administration, number of oocytes and
embryos retrieved. The outcomes were positive dynamics of β-hCG growth and clinical
indicators of pregnancy. Clinical pregnancy was defined as an ongoing pregnancy with
ultrasound imaging of the ovum and fetal heart rate.
Statistical analysis of data was carried out using STATISCA 10 package (Tibco, USA).
Spearman's rank correlation coefficient, Mann-Whitney U test, Pearson's Chi-square test,
Maximum likelihood Chi-square tests were used. p <0.05 was considered statistically
significant.
