Lutckiy A. Optimization of luteal phase support during the in vitro fertilization

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0821U100143

Applicant for

Specialization

  • 14.01.01 - Акушерство та гінекологія

25-01-2021

Specialized Academic Board

ДФ 64.600.010

Kharkiv National Medical University

Essay

The purpose of the study is to optimize the support of the luteal phase to increase the efficiency of infertility treatment with the help of in vitro fertilization. To achieve the purpose of the study we examined 310 patients, who were divided into 3 clinical groups. The first group consisted of fully examined, somatically and gynecologically healthy 50 women who were donors of oocytes. The control group included 10 donors who were in the natural menstrual cycle, whose luteal phases were not supported. To determine the optimal scheme of luteal phase support, all examined donors were divided into 5 subgroups, each included 10 women. After receiving oocytes, all patients of the first group used various progesterone drugs to support luteal phase. To analyze the efficiency of the in vitro fertilization when transferring euploid vitrified blastocysts, we examined 100 women with tubal-peritoneal form of infertility, who made up the third group. Depending on the ultrasound results, the patients were divided into two subgroups 3-a and 3-b, 50 women each. Women of the 3-a subgroup, after ovulation stimulation, were aspirated oocytes, and then fertilized. The obtained blastocysts were subjected to preimplantation genetic diagnosis and cryopreservation on the 5th day of cultivation. After thawing, in the case of ultrasound detection of the corpus luteum in another natural menstrual cycle, we carried out the transfer of vitrified euploid blastocysts. On the basis of Doppler blood flow of uterine vessels, we studied the dynamics of changes in the echo-structure of the endometrium and its functional features before embryo implantation, depending on the scheme of luteal phase preparation. We also studied blood flow in the right and left uterine arteries and a subjective assessment of the degree of vascularization in the myometrium and subendometrial area. Ultrasound and Doppler criteria for blood flow in the uterine, arcuate and radial arteries before treatment were statistically reduced. After luteal phase support in all subgroups there was a significant increase not only in the maximum blood flow velocity, but also the blood flow velocity in diastole, which was close to the control group of women. A significant difference in the reduction of pulsation index (1,6±0,05) and systolic-diastolic relationship (2,6±0,04) was observed in patients who has luteal phase support with highly purified subcutaneous progesterone at a dose of 25 mg and progesterone in the form of vaginal gel 90 mg. When analyzing the features of collagen and fibronectin-synthesizing function of the endometrium in different schemes of luteal phase support, it was found that the optimal conditions for blastocyst implantation during the "implantation window" corresponded to a combination of highly purified subcutaneous progesterone at a dose of 25 mg and 90 mg of progesterone gel. The process of pinopods formation is of great importance for the success of assisted reproductive technologies. On the 5th after oocyte aspiration in patients of the subgroup where luteal phase support was with highly purified subcutaneous progesterone administration 25 mg (1 ml) once daily and 90 mg of intravaginal progesterone gel, there occurred normal development of mature pinopods in 60.0% of cases which was significantly higher than in other observation groups (20-30%) and approached the indicators of the control group (50%). The in vitro fertilization efficiency when using native embryos in various modifications of luteal phase support showed that the best luteal phase support was to use highly purified progesterone for subcutaneous administration in combination with the vaginal form of progesterone gel (90 mg) once a day. Using this method, women in subgroup 2-b significantly increased rates of clinical pregnancy (52%) and the number of live births (46%). The high efficiency of this method of luteal phase support was in the optimal ratio of progesterone metabolites, which had certain advantages for pregnancy. There were no significant differences in the effectiveness of treatment cycles (in natural, or with the protocol of hormone replacement therapy and luteal phase support) in the transfer of vitrified euploid blastocysts in the studied subgroups, but the incidence of pregnancy was higher in natural cycles with the addition of progesterone than in artificial cycles with agonists. Thus, the scientific novelty of the thesis is in the analysis of the in vitro fertilization efficiency depending on the method of luteal phase support using native embryos.

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