RU2449274C1 - Method of determining readiness of hemostasis system in women included in programme of extracorporal fertilisation and transfer of embryo - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: on 20-24 day of menstrual cycle additional analysis of vascular-endothelial growth-factor (VEGF), homocysteine, endothelin, plasminogen activation inhibitor of first type (PAI-1), tissue plasminogen activator (t-PA) is carried out and if they correspond to the norm of vascular-endothelial growth factor (VEGF) within 30-600 pg/ml, homocysteine 5-12 mcmol/l, endothelin 8-14 fmol/ml, plasminogen activation inhibitor of first type (PAI-1) 7-40 ng/ml, tissue plasminogen activator (t-PA) 5-12 ng/ml, conclusion about readiness of woman's hemostasis system for inclusion into programme of extracorporal fertilisation and transfer of embryo is made.

EFFECT: method makes it possible to increase efficiency of programme of extracorporal fertilisation and transfer of embryo due to correcting therapy of hemostasis parameters in case of necessity.

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Description

The invention relates to medicine, namely to reproductive gynecology, and may find application in the program of in vitro fertilization (IVF) and embryo transfer (PE).

The final stage of all in vitro fertilization (IVF) procedures is blastocyst implantation after the woman has transferred her embryo.

Today it is well known that the success of implantation depends on the temporal correspondence between the stage of embryo development and the period of endometrial receptivity. The endometrium undergoes constant changes during the menstrual cycle under the influence of estrogen and progesterone in accordance with changes in their concentration. For the successful onset of implantation, the development of the endometrium must be synchronous with the development of the embryo. It can be assumed that the embryo, in turn, also somehow contributes to the maturation of the endometrium. Violations of this balance can alter the susceptibility of the endometrium and thus disrupt the implantation process. As you know, implantation occurs only when the endometrium, which is under a certain hormonal effect, enters the phase of susceptibility to blastocyst implantation. This phase is quite short and should coincide with the development of the embryo to the blastocyst stage, thus determining a short time interval when implantation is possible. The period during which the endometrium remains receptive for embryo nidation is called the “implantation window”. The proposed window for human implantation theoretically coincides with the 20-22nd day of an ideal 28-day menstrual cycle.

The program for preparing for IVF and PE includes women with an undisturbed menstrual cycle, having, according to hysterosalpingography, passable fallopian tubes and uterus without any pathologies, normal values of sex hormones and thyroid hormones, hemostasis indicators (coagulogram, antiphospholipid syndrome) investigated by infectious and immune statuses (“Treatment of female and male infertility. Assisted reproductive technologies” under the editorship of V.I. Kulakov, MIA, M., 2005). The readiness of the endocrine system (normal values of the active fraction of growth hormone (patent No. 2316771, 2008).

The objective of the invention is to increase the efficiency of the IVF and PE program.

The problem is solved by the method, which additionally determines the markers of local hemostasis on days 20-24 of the menstrual cycle, vascular endothelial growth factor (VEGF), homocysteine, endothelin, type I plasminogen activation inhibitor (PAI-1), tissue plasminogen activator (t-PA) and when the value of VEGF in the range of 30-600 pg / ml, homocysteine 5-12 μmol / l, endothelin 8-14 fmol / ml, PAI-1 7-40 ng / ml, t-PA 5-12 ng / ml conclude that the woman’s hemostasis system is ready for inclusion in the in vitro fertilization program and embryo renos.

As we have established, in some cases, despite the correspondence of the clinical and laboratory picture, IVF and PE attempts were also unsuccessful. To clarify the causes of unsuccessful IVF attempts, we conducted an additional study of hemostasis for vascular endothelial growth factor (VEGF), homocysteine, endothelium, tissue plasminogen activator (t-PA), and type I plasminogen activation inhibitor (PAI-1).

Studies of these hemostasis indicators in a group of 36 women with successful implantation of a fetal egg showed that for a successful attempt to implant a fetal egg, the value of vascular endothelial growth factor should be in the range of 30-600 pg / ml, homocysteine 5-12 μmol / l, endothelin 8 14 fmol / ml, an inhibitor of plasminogen activation of the first type 7-40 ng / ml, tissue plasminogen activator 5-12 ng / ml, with values lower or higher than the indicated parameters, implantation attempts are usually unsuccessful.

The following examples illustrate the method of the invention.

Example 1

Patient D., 34 years old, turned to the ART department (assisted reproductive technologies) at the Obstetrics and Gynecology Clinic named after V.F.Snegireva with a diagnosis of Primary infertility for 12 years. A history of 5 unsuccessful attempts to stimulate ovulation under the IVF and PE program.

A complete standard clinical laboratory examination was carried out, the indicators correspond to the norm. Additional studies of markers of local hemostasis on day 22 of the menstrual cycle were prescribed. With the detected values of VEGF indicators 640 pg / ml, homocysteine 22 μmol / l, endothelin 5 fmol / ml, PAI-1 61 ng / ml, t-PA-2 ng / ml, a conclusion was made about the possible failure of implantation of the fetal egg in the IVF program and PE. A stimulation cycle was carried out, however, as expected from these indicators of local hemostasis, pregnancy did not occur.

Example 2

Patient M., 42 years old, turned to the ART department with a diagnosis of Primary Infertility for 16 years. A history of 8 unsuccessful attempts to stimulate ovulation under the IVF and PE program. A complete standard clinical laboratory examination was carried out. Additional studies of markers of local hemostasis on day 22 of the menstrual cycle were prescribed. The study showed a VEGF score of 800 pg / ml, homocysteine 16 μmol / L, endothelin 3 fmol / ml, PAI-1 70 ng / ml, t-PA 3 ng / ml. With these indicators, it was also concluded that the implantation of the ovum was unsuccessful in the IVF and PE program. A stimulation cycle was carried out, but pregnancy did not occur.

In another group of 30 women, who also studied these indicators with the timely prevention of various complications, corrective therapy of hemostasis was performed with preparations of B vitamins, folates and anticoagulants, the onset of implantation of the ovum was observed in 55-75%.

Example 3

Patient M., 29 years old, turned to the ART department with a diagnosis of Primary Infertility for 7 years. In the history of 3 unsuccessful attempts to stimulate ovulation according to the IVF and PE program. A complete standard clinical laboratory examination was carried out, the indicators correspond to the norm. Additional studies of markers of local hemostasis on day 22 of the menstrual cycle were prescribed. With the detected VEGF indices of 712 pg / ml, homocysteine 14 μmol / l, endothelin 2 fmol / ml, PAI-1 54 ng / ml, t-PA 4 ng / ml, corrective therapy with vitamin B preparations, folates and anticoagulants was performed. After the therapy, markers of local hemostasis, VEGF 615 pg / ml, homocysteine 11 μmol / l, endothelin 4 fmol / ml, PAI-1 42 ng / ml, t-PA 6 ng / ml were re-taken, pregnancy was confirmed after stimulation Ultrasound

Example 4

Patient G., 37 years old, turned to the ART department with a diagnosis of Primary Infertility for 14 years. A history of 5 unsuccessful attempts to stimulate ovulation under the IVF and PE program. A complete standard clinical laboratory examination was carried out, the indicators correspond to the norm. Additional studies of markers of local hemostasis on day 22 of the menstrual cycle were prescribed. The values of VEGF were 626 pg / ml, homocysteine 18 μmol / l, endothelin 5 fmol / ml, PAI1 40 ng / ml, t-PA 2 ng / ml. Corrective therapy was carried out with preparations of B vitamins, folates and anticoagulants. After the therapy, local hemostasis markers, VEGF 540 pg / ml, Homocysteine 11 μmol / L, Endothelin 8 fmol / ml, PAI-1 34 ng / ml, t-PA 8 ng / ml were also taken again, pregnancy was stimulated after ultrasound confirmed and ended in childbirth.

Thus, the method according to the invention improves the efficiency of the in vitro fertilization and embryo transfer program by 5-7%.

Claims (1)

A method for determining the readiness of the hemostasis system in women included in the program of in vitro fertilization and embryo transfer, which consists in the fact that additional studies are carried out on days 20-24 of the menstrual cycle of the vascular endothelial growth factor, homocysteine, endothelin, type I plasminogen activation inhibitor, tissue activator plasminogen and with a value of vascular endothelial growth factor in the range of 30-600 pg / ml, homocysteine 5-12 μmol / l, endothelin 8-14 fmol / ml, plasmin activation inhibitor the first type of gene 7-40 ng / ml, tissue plasminogen activator 5-12 ng / ml conclude that the woman’s hemostasis system is ready for inclusion in the program of in vitro fertilization and embryo transfer.