The method of in vitro fertilization has long moved from the world of fiction to modern reality. After all, a huge number of men and women were able to realize their dream of becoming parents with its help.
All stages of such a pregnancy are essentially the same as during natural fertilization. However, there is one significant difference between them: IVF creates optimal conditions for successful conception. One of these artificially created conditions is stimulation before IVF. Thanks to stimulation, reproductive specialists have the opportunity to obtain the maximum possible number of mature, viable eggs, which increases the chances of pregnancy significantly.
What is an in vitro fertilization program?
Thanks to the revolutionary development of assisted reproductive technologies, a method of treating infertility has emerged that has given great hope to infertile couples. This is a method of in vitro fertilization, embryo transfer, which today is the most effective method of treating infertility, helping even in the most seemingly hopeless situations. IVF, embryo implantation is used for absolute female infertility (in the absence or complete obstruction of both fallopian tubes), for male infertility, for infertility of unknown cause, as well as for ineffective conservative or surgical treatment of other forms of infertility. Therefore, doctors believe that it is impossible to continue treating infertility with other methods for more than 1.5–2 years if their ineffectiveness is obvious. The sooner a couple contacts an in vitro fertilization clinic, the higher their chances of success. During in vitro fertilization, after stimulation of the woman's ovaries, several follicles with eggs mature. Directly in vitro fertilization is carried out in this way: the doctor punctures the ovary, extracting eggs, which are then fertilized with the sperm of the husband or donor outside the mother’s body. If the quality of the spouse's sperm is reduced, a single sperm is injected using a microneedle (ICSI method). After a few days, embryo transfer takes place: the embryos obtained through IVF fertilization are transferred into the woman’s uterine cavity. Next, the embryo attaches and the embryo in the uterus continues to develop. After embryo transfer, one attempt at IVF fertilization, embryo implantation gives a chance of conception from 20% to 30%, which is even slightly higher than the average rate of pregnancy naturally. The likelihood of conception and successful development of the embryo during the procedure after embryo transfer depends on the age of the spouses, their state of health, the quality of the drugs used, the quality of the resulting embryos, as well as some other factors. The correct day for embryo implantation is determined by a specialist doctor. After embryo transfer, the days after embryo transfer should be supervised by a specialist. The failure of one attempt at IVF fertilization does not mean that this method - embryo transfer - was ineffective. Each subsequent IVF attempt and embryo implantation significantly increases the total chances of a successful pregnancy after embryo transfer. Within a year of treatment, in vitro fertilization after embryo transfer gives an almost ninety percent chance of getting pregnant. In the three decades since the birth of Englishwoman Louise Brown, the first child born from an egg fertilized in vitro (1978), more than three million children have been born using this method. Modern assisted reproductive technologies and embryo transfer have already helped millions of infertile couples around the world. We hope that they will help you too. If you do not have the funds to transfer embryos, then you can try to perform in vitro fertilization for free, or transfer embryos using a special state program. However, it should be remembered that free in vitro fertilization is much more difficult than a paid procedure - since if you fail, you will wait a long time for the next chance to get free in vitro fertilization. Good luck!
The effectiveness of a short IVF protocol
When comparing the effectiveness of the short and long protocols, the following pattern emerges:
The short protocol is more indicated for male infertility, while in women, disturbances in the reproductive system are minimal. In this case, after stimulation, full-fledged oocytes suitable for fertilization mature in the ovaries.
Gentle schemes of a short protocol with a low hormonal load do not guarantee uniform maturation of all follicles, and often after puncture it is difficult for the doctor to select mature and viable eggs for IVF.
Important. According to statistics, with a long protocol the chances of successful conception are higher than with a short one.
Program outline. Embryo implantation. Before and after embryo transfer
The IVF program consists of several stages. Each stage is important in its own way, so you need to treat it very responsibly, strictly following all the doctor’s recommendations.
Stage I Determination of the in vitro fertilization program, including treatment tactics after a preliminary examination.
Stage II Preparing spouses for such an important procedure as IVF fertilization: correction of hormonal abnormalities, including spermatogenesis disorders, treatment of infections
Stage III Stimulation of superovulation, ultrasound monitoring (10–30 days).
Stage IV Introduction of human chorionic gonadotropin (hCG) for the final maturation of eggs before in vitro fertilization (1 day).
Stage V Follicle puncture, egg collection, sperm donation. Fertilization of an egg with the sperm of a spouse or donor (1 day). Stage VI Cultivation of embryos, observation of embryo fragmentation (2–5 days).
Stage VII On the selected day of embryo transfer - transfer of embryos into the uterine cavity, after embryo transfer - freezing of the remaining embryos as necessary (1 day).
Stage VIII Days after embryo transfer - hormonal support for early pregnancy after embryo transfer. It is important that the implantation of the embryo is successful. (up to 10-14 weeks).
Stage IX Pregnancy test associated with the detection of the blood hormone hCG (2 weeks after embryo transfer, IVF fertilization).
Stage X ultrasound – diagnosis of pregnancy (3 weeks after embryo transfer, in vitro fertilization procedure).
Stage XI Pregnancy management.
XII stage of Childbirth (maternity hospital).
Preparation for the procedure
Lifestyle for both spouses
In order for the body to be ready for such a procedure as embryo transfer and the upcoming pregnancy, it is necessary to maintain a healthy lifestyle. The diet should be varied, rich in vitamins, proteins, containing a moderate amount of fats, as well as carbohydrates. No strict diets. When you need to donate blood for biochemical or hormonal studies, you can have breakfast only after drawing blood. It is recommended to take vitamin and mineral complexes intended for pregnant women. An alternative is to take folic acid, potassium iodide, and vitamin E in small doses a month before the start of the program. Avoid taking medications that are contraindicated during pregnancy. Smoking, even passive smoking, should be avoided. You should not drink more than two cups of coffee per day, and alcohol consumption should be kept to a minimum. Avoid hot baths, steam baths, saunas. Try to lead an active, mobile lifestyle. Try to ensure that the treatment has as little impact on your mood as possible. Avoid significant stress, as well as physical or psychological stress. After embryo transfer, the importance of a healthy lifestyle increases even more
Sexual contacts
The general nature of sexual activity during the in vitro fertilization procedure should not change. You can have sex with the same frequency as always. But you need to abstain from sexual intercourse for 3-4 days so that your husband can accumulate a sufficient amount of sperm. Also, the spouse should refrain from masturbation. Abstinence should continue for about seven days until the day of embryo transfer arrives. Sexual intercourse after embryo transfer should be avoided until pregnancy tests show that the embryo has been successfully implanted and the embryo is developing properly. Both spouses should try to avoid casual sex. Detected genital infections must be treated, so subsequent sexual intercourse should be carried out with a condom. When in vitro fertilization is performed, after embryo transfer, pain during sexual intercourse is possible due to enlarged ovaries.
Minimum preliminary examination
When you are indicated for an IVF procedure or embryo transfer, a number of studies can be done at your place of residence. Find out the required minimum examinations. Usually this is a spermogram of the spouse, a hormonal analysis, an image of the uterus, fallopian tubes, a blood test, and a vaginal smear analysis for the presence of infectious diseases. When you come to your initial appointment with a doctor, do not forget to take with you all the available results of previous examinations, extracts from medical records, etc. All this will be needed for the embryo implantation to be successful. Infections Before the procedure, it may be necessary to be examined for some infections that, after embryo transfer, pose a danger to the embryo and have a negative impact on its development, as well as on the pregnancy. These include, for example, herpes, cytomegalovirus, rubella, toxoplasmosis. These infections are widespread, but often occur hidden. The scope of diagnosis is determined by the attending physician.
Hormonal examination Often, infertility is accompanied by hormonal abnormalities. Their timely detection, as well as correction, can increase not only the likelihood of pregnancy after embryo transfer, but also the chances of its favorable course. Most hormones are tested from days 1 to 5 of the menstrual cycle. Therefore, the first visit should occur during this period. Blood is donated from a vein, usually in the morning, on an empty stomach.
Visit to an andrologist, sperm examination
Treatment of infertility with IVF involves a mandatory examination by an andrologist, including sperm testing. Before a sperm analysis, the spouse must follow some rules: abstain from sexual activity for 3 to 7 days (optimally 5), do not drink alcohol, do not take steam, no hot baths, do not urinate for two hours before visiting the doctor, eat only low-fat, non-spicy foods.
Planning visits to the doctor Treatment with IVF and embryo transfer takes place on an outpatient basis, but requires discipline and punctuality from patients. Before starting the program, plan your activities so that you do not have night shifts so that you can undergo ovulation stimulation (for 2-4 weeks), and then come for puncture and embryo transfer on the day of embryo implantation. The presence of the husband is required for a preliminary examination and sperm donation during follicle puncture. After the embryo transfer, you will be issued a sick leave certificate.
Agreements If you are planning to start treatment with IVF or other methods of assisted reproduction, which include ICSI, artificial insemination, fertilization with donor sperm, egg donation, surrogacy, then first decide with your doctor all the ethical and legal issues that concern you. For each type of treatment, a legal agreement is concluded with the clinic, which must be signed by both spouses.
Possibilities for improving the effectiveness of IVF and PE in patients of advanced reproductive age
The prevalence of infertile marriage in Russia is more than 15%, and this figure is growing from year to year. That is why this problem is receiving increasing attention at the state level as part of the support of modern medical technologies, including programs aimed at overcoming infertility, from which fairly high final results are expected: the percentage of pregnancy and an increase in the number of “take baby homes” for funded cycles. In recent years, there has been a tendency towards an increase among married couples in the proportion of patients of late reproductive age who seek pregnancy and childbirth (according to the American Society of Reproductive Medicine (ASRM) - up to 12.3%). According to the Register of the Russian Association of Human Reproduction (RAHR) from 2014, the percentage of patients over 40 years of age who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) programs was 15.05%, embryo cryotransfer (E) - 11 .3% of programs performed using donor oocytes (DO) in the age group over 40 years old was 49.7% [1]. Demographic studies in a number of countries show that, for various socio-economic reasons, an increasing number of women are postponing pregnancy until the end of their reproductive years. Women strive to obtain higher education, have an intensive work schedule outside the home, get married late and are in no hurry to have children (Boyarsky K. Yu., 2009) [2]. In addition, the treatment of a number of patients at a later reproductive age is due to such social aspects as the death of a child (children) and remarriage. The main reason for patients of late reproductive age seeking treatment for infertility, according to T. A. Nazarenko and N. G. Mishieva (2014), is remarriage - 42%. 40% of women sought treatment for infertility at an early reproductive age, but long-term ineffective treatment for 10 years or more with a change in a number of medical institutions led to the fact that these patients sought specialized help already at a late reproductive age. Delayed childbearing at the request of a woman accounted for only 13%; the death of an only child was a motivation for 5% of women. The identified reasons for referral are presented in Fig. 13].
The effectiveness of IVF programs is largely determined by age and ovarian reserve. Ovarian reserve in patients of the older age group is usually reduced. Ovarian reserve is understood as the functional reserve of the ovary, which determines the ability of the latter to develop a healthy follicle with a full-fledged egg (Boyarsky K. Yu., 2005). Indicators of low ovarian reserve (Nazarenko T. A., Krasnopolskaya K. V., 2012) - a predictor of poor ovarian response to stimulation of superovulation are the following parameters: age over 35 years; duration of the menstrual cycle is 24–26 days; follicle-stimulating hormone (FSH) level more than 10 IU; the number of basal follicles is less than 10 mm on days 2–3 of the cycle, less than 5 in each ovary; ovarian volume is less than 8 cm3 [4]. Today, it is customary to predict a poor ovarian response based on the recommendations of the European Society of Human Reproduction and Embryology (ESHRE, Bologna criteria), which include:
- previous episode of poor ovarian response (≤ 3 oocytes) with standard dosages of gonadotropins;
- abnormal ovarian reserve with antral follicle count < 5–7 or anti-Mullerian hormone (AMH) < 0.5–1.1 ng/ml;
- women over 40 years of age or the presence of other risk factors for poor response, such as ovarian surgery, genetic defects, chemotherapy, radiation therapy and autoimmune diseases.
Patients who have at least two of the following criteria are classified as having low ovarian reserve and, as a result, poor response.
The average effectiveness of using assisted reproduction methods per treatment cycle is 30–35% (Kulakov V.I. et al., 2000), according to the RAHR register (2014) - 40%. However, these indicators do not apply to the group of patients over 35 years of age (senior reproductive age), who have generally reduced ovarian reserve rates and low efficiency of IVF programs - less than 10–20% (Nazarenko T. A., Krasnopolskaya K. V., 2012; Nikitin S. V. et al., 2015; Rudakova E. B. et al., 2015, etc.). In the work carried out in the Department of Assisted Reproductive Technologies of the Moscow Medical Center, Balashikha, comparing the biological indicators of IVF cycles for 2014 in the age groups up to 38 years (1st group) and over 38 years (2nd group), the following indicators are reflected: one treatment cycle (Table 1). The number of eggs obtained was (p < 0.05): 10.6 ± 5.8 in group 1 and 4.7 ± 1.1 in group 2, respectively; number of mature eggs (p < 0.05) - 7.3 ± 4.6 and 3 ± 2.6, respectively; number of embryos obtained (p < 0.05): 7.4 ± 4.4 and 3.7 ± 1.1, respectively; the number of obtained embryos of the highest quality (p < 0.05) was 2.4 ± 2.4 and 1.1 ± 0.3, respectively. Clinical pregnancy occurred in 39.8% in the 1st age group and 21.4% in the 2nd age group [5].
Improving the results of IVF programs with a “poor response” is a task that attracts the attention of all specialists who use methods of assisted reproductive technologies to treat infertility. Researchers offer different treatment options and regimens both as preliminary preparation and during ovarian stimulation [6]. Various measures may be possible ways to solve this problem. The use of increased doses of gonadotropins in superovulation stimulation protocols. The dose of an ovulation inducer is typically 400–450 IU, a combination of recombinant follicle-stimulating hormone (rFSH) and human menopausal gonadotropin (hMG) or, conversely, low-dose superovulation stimulation protocols, so-called “soft” protocols. Improving protocols for stimulating superovulation (long protocol with a reduced dose of agonists-releasing hormones (AG-RG); modified protocol with antagonists of gonadotropin-releasing hormone (antGn-RG), combination of AG-RG and antGn-RG in the protocol), IVF in natural cycle. Using modern protocols with cryopreservation of obtained eggs followed by transfer of thawed embryos in a cycle of hormone replacement therapy (double stimulation). Methods of using ovarian response stimulators before superovulation stimulation protocols. Application of the technique of maturation of eggs outside the body (IVM) in patients with IVF failures, including in the absence of mature oocytes.
The combination of rFSH and hMG is based on the presence of luteinizing hormone (LH) in menotropins, which prevents an increase in endogenous LH levels. The argument of supporters of menotropins was the need to use the positive effects of LH in the late follicular phase with a “poor response” [7].
Low-dose (“mild”) stimulation protocols are based on the administration of small doses (100–200 IU) if 2–3 follicles are visualized on days 7–8 of the natural menstrual cycle. When the follicles reach a diameter of 14 mm, additional GnRH antigen is prescribed up to and including the day of introduction of the ovulation trigger. “Soft” stimulation protocols provide a reduction in the course dose of gonadotropins, which helps reduce the cost of the controlled stimulation stage in the implementation of the IVF program. It should be noted that when using these protocols, the frequency of “poor response” increases markedly and it is reasonable to prescribe them to older patients with extremely reduced ovarian reserve indicators and a confirmed poor response (when no more than two oocytes were received) in previous attempts at stimulation using more aggressive protocols .
Long protocol with dose reduction of GnRH: There have been reports that reducing the dose of GnRH by 2-4 times can improve the ovarian response and increase the effectiveness of treatment. However, no convincing evidence has been provided regarding the benefits of such tactics.
Modified protocol with antGn-RH: it is proposed to administer antGn-RH (0.25 mg) once on the 1st day of the menstrual cycle, then continue stimulation as usual and use antGn-RH when the follicle reaches a diameter of 14 mm. The purpose of this regimen is to desensitize the hypothalamic-pituitary system in order to form a pool of follicles for stimulation by gonadotropins. The effectiveness of this technique has not been reliably assessed.
Combination of AG-RH and antGn-RH in the protocol: when ovarian stimulation is performed, antGN-RH is prescribed from 19–21 days of the previous menstrual cycle until the 2nd day of the next one, then gonadotropins are added. From the moment the growing follicles reach a diameter of 14 mm, GnRH antigen is prescribed, which is used until the ovulation trigger is introduced. This protocol has not gained popularity due to high cost and lack of benefits compared to other drug administration regimens. On the contrary, when using the described scheme, many specialists have established the fact of frequent cancellation of cycles.
Double stimulation: when studying the mechanisms leading to the recruitment of follicles, it was found that their maturation is wave-like, and there are only 3-4 such waves per cycle, the first of which begins in the luteal phase. Therefore, it was decided to try to continue stimulation with small doses of gonadotropic hormones after oocyte puncture (small doses give a uniform growth of a larger number of follicles, while large doses give a sharp growth of just a few follicles). This yielded results and made it possible to obtain oocytes twice in one cycle. The embryos are frozen and transferred in subsequent cycles. The effectiveness is debatable. The rationality of using this protocol is due to the receipt of a larger number of oocytes due to two stimulations in one menstrual cycle and, accordingly, embryos. However, this technique is very expensive.
It should be noted that IVF in a natural cycle is characterized by a low pregnancy rate even in young patients with a completely normal ovarian reserve, since up to a third of the follicles may not contain a full-fledged egg. In addition, oocytes obtained in natural cycles are characterized by a relatively low frequency of fertilization (no more than 70%), and embryos obtained from such oocytes have a low frequency of cleavage (no more than 50%) and implantation (no more than 15%). All this leads to the fact that the effectiveness of such cycles in terms of pregnancy rates is at the level of 3–4%. The recommendation on the advisability of using IVF in a natural cycle in women of older reproductive age has the same reasoning as “soft” protocols - saving on gonadotropic hormone preparations [8].
When using the IVM proposed by the authors, oocytes are obtained by puncturing follicles with a diameter of 10–12 mm. Next, they are provided with ripening in special media, their subsequent fertilization (using ICSI), and then the resulting embryos or blastocysts are transferred [9].
However, there is no clear evidence base for the effectiveness of the methods described above. There are some encouraging studies by foreign and domestic specialists (A. A. Smirnova et al., 2016; Baikoshkarova S. B. et al., 2015; Nikitin S. V. et al., 2016, S. Yu. Kalinchenko et al. , 2016; Kuang Y. et al., 2014; Moffat R. et al, 2014; Ubaldi FM, 2016) specifically in patients with low ovarian reserve in the older age group with a “poor response” prognosis.
A number of authors describe methods of using ovarian response stimulants before superovulation stimulation protocols: androgen and estrogen priming, the use of growth hormone (GH), oral contraceptives, hormone replacement therapy, gestagens, dietary supplements.
According to reports by E. V. Krstic (2010) and K. V. Krasnopolskaya et al. (2010), “androgen priming” is useful specifically for those “age-related” patients who have a decrease in the androgen-secreting function of the ovaries, manifested in abnormally low values of total testosterone (less than 1 nmol/l). According to the observation of these authors, the hypoandrogenic state is an independent risk factor for “poor response”, which does not correlate with a decrease in ovarian reserve. For such patients, these authors recommend prescribing the testosterone-containing drug Androgel (in a daily dose of 2.5 g of gel containing 25 mg of testosterone) for 15–20 days before the start of gonadotropin stimulation, which reduces the incidence of “poor response.” The authors associate the mechanism of the positive effect of “androgen priming” in such patients with the ability of androgens to activate the early recruitment of follicles into the maturing cohort, increase the expression of FSH receptors on granulosa cells of small antral follicles and maintain adequate sensitivity of FSH receptors at all hormonal-dependent stages of folliculogenesis.
The authors who proposed the method of estrogen priming (estrogens in the luteal phase of the previous cycle) proceeded from the fact that the cohort of follicles that will enter active folliculogenesis in the next menstrual cycle is formed in the middle of the luteal phase of the previous one. The administration of estrogens during this period, according to the developers of this technique, can prolong the stimulating effect of FSH in the luteal phase of the cycle, as well as increase the level of estrogen production by growing follicles, ensuring their faster growth.
There are very few reports on the possible effect of growth hormones (GH) on ovarian function. There are isolated publications by a number of authors (Anshina M. B., 1998; Kucuk T. et al., 2008; Kolibianakis E.M. et al., 2009).
The point of prescribing oral contraceptives in a monophasic mode is to temporarily inhibit the hypothalamic-pituitary-ovarian system, after which in the subsequent cycle the so-called rebound effect is likely, i.e. activation of the activity of this system. The presented technique is often effective in young patients who experience oligomenorrhea and anovulation against the background of sufficient or high concentrations of estrogen. At the same time, the prescription of oral contraceptives to women with reduced ovarian reserve and concomitant hypoestrogenism is unlikely to be a promising method for reliably preventing a “poor response.”
The administration of hormones in a cyclic mode (hormone replacement therapy) - estrogens in increasing doses in the follicular phase, progesterone preparations together with estrogens in the luteal phase - simulates physiological fluctuations in the levels of sex steroids during the menstrual cycle. This may be useful in promoting endometrial transformation, but is unlikely to have a positive effect on the subsequent ovarian response to stimulation of ovarian function.
Progestogens as a pretreatment are likely to have no bearing on the subsequent ability of the ovaries to respond to stimulation with gonadotropins. Indications for prescribing these drugs are the presence of follicular cysts in the ovaries, the need to fix a menstrual-like reaction and ensure adequate transformation of the endometrium.
Nonspecific remedies - dietary supplements, phytoestrogens, homeopathic drugs - are now quite widely used not only by doctors, but also by patients who self-medicate. With a “poor response” from the ovaries and/or multiple failed attempts, IVF is a “remedy of desperation.”
We have to admit that to date, the results of various meta-analyses have not confirmed the reliable effectiveness of any specific drugs [10].
Other possible ways to address the effectiveness of programs in patients of the older age group with a poor response prognosis may be the use of complex IVF programs with the parallel use of donor oocytes (native or vitrified) or donor embryos. Such IVF programs, carried out at the expense of the Compulsory Medical Insurance Fund, are possible with the parallel use of donor oocytes (native or vitrified) or donor embryos in this program at the expense of the patient herself after the married couple has signed all the necessary legal documents. At the same time, at the embryo transfer stage, at least two embryos are always transferred. One embryo is obtained by fertilizing the patient's oocytes (usually of poor quality) with the husband's sperm, the other is either obtained by fertilizing donor oocytes with the husband's sperm (usually of good quality), or a donor embryo. If there are no embryos obtained from fertilization of the patient's oocytes with the husband's sperm, two embryos obtained by fertilizing donor oocytes with the husband's sperm or two donor embryos are transferred.
The purpose of this study was to give a comparative description of the effectiveness of basic IVF and ET programs carried out in conditions of state support at the expense of funds from the Compulsory Medical Insurance Fund and complex programs with combined financing (along with funds from the Compulsory Medical Insurance Fund, parallel payment for pre-treatment, prenatal treatment or a donor program from one’s own funds) for patients older reproductive age with low ovarian reserve and a poor response prognosis.
Materials and research methods
We analyzed the outcomes of programs carried out at the expense of the Compulsory Medical Insurance Fund on the basis of the Department of Assisted Reproductive Technologies of the Moscow Medical Center for 2015 and 2021. in patients of advanced reproductive age with a prognosis of “poor response”, who were divided into two groups. The 1st group consisted of 69 patients who underwent a basic IVF and PE program in 2015, the 2nd group included 60 patients who underwent both a basic and a comprehensive IVF and PE program in 2021. A 2a subgroup was also identified — 26 patients out of 60 who underwent a comprehensive IVF and PE program. All married couples were examined according to a single standard (Order No. 107n of the Ministry of Health of the Russian Federation), and during the period of the program - in accordance with Order No. 556 of October 30, 2012.
The selection of patients for assisted reproductive technology programs at the expense of the Compulsory Medical Insurance Fund was carried out according to the criteria recommended and set out in the Information and Methodological Letter of the Ministry of Health of the Russian Federation and the Federal Compulsory Medical Insurance Fund No. 15-4/10/2-1777 and No. 1359/30-4 dated March 18. 2014 “On the referral of citizens of the Russian Federation for the IVF procedure in 2014”, as well as in accordance with Order of the Ministry of Health of the Russian Federation No. 916n dated December 10, 2013 “On the list of types of high-tech assistance.” The criteria for selecting patients for complex programs with parallel use of donor oocytes was a decrease in ovarian reserve, determined by the Bologna ESHRE criteria. The main regulatory documentation that makes it possible to carry out complex programs was Order of the Ministry of Health of the Russian Federation No. 107n dated August 30, 2012, Order of the Ministry of Health of the Russian Federation No. 556 dated October 30, 2012, information and methodological letter of the Ministry of Health of the Russian Federation dated March 29, 2016. In Order No. 107n dated 08/30/2012 “On the procedure for using assisted reproductive technologies, contraindications and restrictions on their use”, paragraph 22a: “The restrictions for the use of the basic IVF program are a decrease in the ovarian reserve (according to ultrasound data and the level of AMH in the blood)” ; in paragraph 22b o. Order No. 556 of October 30, 2012 “On approval of the standard of medical care for infertility using assisted reproductive technologies” outlines the procedures and medications of the basic IVF program, paid for from the funds of the Compulsory Medical Insurance Fund. The information and methodological letter of the Ministry of Health of the Russian Federation and the Compulsory Medical Insurance Fund dated March 22, 2021 “On the referral of citizens of the Russian Federation for the IVF procedure” indicates the possibility, within the framework of the basic IVF program financed by the Compulsory Medical Insurance Fund, to use additional medical services, payment for which is made at the expense of other means. “Payment for medical services during the IVF procedure within the framework of the basic compulsory medical insurance program, not provided for by the standard of medical care for infertility using assisted reproductive technologies ... (use of donor oocytes, donor sperm, donor sperm, donor embryos, surrogacy, cryopreservation and storage of one’s germ cells , tissues of reproductive organs and embryos) is produced additionally at the expense of personal funds and other funds provided for by the legislation of the Russian Federation.”
Stimulation of superovulation was carried out according to a long protocol with mini-doses of AG-RG (Diferelin daily form 0.1 mg was administered 0.05–0.025 mg). The choice of the drug was determined by its safety, effectiveness and simple storage conditions). Ovarian stimulation was carried out with recombinant human follicle-stimulating hormone Gonal-F. The choice of the drug was determined by its quality, effectiveness and a variety of convenient forms and doses of administration (75 IU bottles, 300 IU syringe pens with a decreasing minimum dosage and step of drug administration). Along with recombinant follicle-stimulating hormone, urinary gonadotropins (Menopur) were used to optimize follicle maturation. The daily dose of GT is 300 IU. rHCG was used as an ovulation trigger - Ovitrel 250 mcg. Luteal phase support was provided with micronized progesterone (Utrozhestan). The preparation of the endometrium in the programs was carried out with transdermal forms of estrogens. The criteria for prescribing estrogen drugs were endometrial thickness according to ultrasound and hormonal profile. The choice of drug was determined by ease of administration.
Research results
All patients before the program were examined in accordance with Order of the Ministry of Health of the Russian Federation No. 107n dated August 30, 2012, and during the program - in accordance with Order No. 556 dated October 30, 2012. According to the main indicators of ovarian reserve, average age, and anamnestic data, the groups were comparable. The average age of patients in the first group was 39.8 years, in the second group - 40.1 years (Fig. 2). The indicators of ovarian reserve in the first group were: FSH level - 11.2 IU/l, AMH - 0.3 ng/ml, number of antral follicles determined by ultrasound - 4.8. In the second group, these indicators were: FSH - 10.8 IU/l, AMH - 0.32 ng/ml, number of antral follicles - 5.1 (Fig. 3).
In patients of groups 1 and 2, female infertility was combined with a male factor - asthenoteratozoospermia in various combinations of moderate severity in 42%.
The embryos were cultivated for up to 5 days, and their quality was assessed using the Gardner scale. The number of obtained oocytes/mature oocytes per patient was (p < 0.05): in group 1 3.7 ± 1.1/2.7 ± 1.8, in group 2 — 4.7 ± 2.2/4.1 ± 1.2, in group 2a - 7.7 ± 3.4/5.7 ± 2.4.
The number of embryos obtained per patient/among them embryos of the highest quality (p < 0.05): in group 1 - 2.1 ± 1.1/1.1 ± 0.4, in group 2 - 2, 9 ± 1.4/1.8 ± 0.8; in group 2a - 4.4 ± 1.8/2.7 ± 1.2. In all patients, embryo transfer was carried out on the 5th day of cultivation.
During complex programs, two embryos were transferred. One embryo is obtained by fertilizing the patient’s oocytes with her husband’s sperm (of medium or low quality), the second is a donor embryo, obtained by fertilizing donor oocytes with her husband’s sperm (high quality). In programs using donor embryos, high quality embryos were transferred. In the absence of “own” embryos, two donor embryos or embryos obtained by fertilizing donor oocytes with the husband’s sperm were transferred. The effectiveness of the IVF program (pregnancy rate) was: in group 1 - 11.6% per cycle; in group 2 - 21.6% per cycle (13), in group 2a - 38.4% per cycle (10) (Fig. 4).
conclusions
A comparative description of the effectiveness of basic IVF and ET programs carried out in conditions of state support at the expense of funds from the Compulsory Medical Insurance Fund and complex programs with combined financing (along with funds from the Compulsory Medical Insurance Fund, parallel payment for pre-treatment, prenatal care or a donor program from one’s own funds) was carried out in patients of older reproductive age with low ovarian reserve and poor response prognosis. In general, during the reporting period, the effectiveness of programs completed in 2021 amounted to 11.6%, and in 2021 - 21.6%, that is, an increase of 10%. Moreover, the effectiveness of only comprehensive programs is comparable to the effectiveness of programs for patients under 35 years of age and is equal to 38.4%. This suggests that age is an important factor in the effectiveness of IVF and ET programs, determining the number of oocytes obtained through stimulation of superovulation, the quality of transferred embryos, and the incidence of induced pregnancy. The use of comprehensive IVF and ET programs with government support in patients over 38 years of age significantly improves their effectiveness, and also allows patients to try to fully use their ovarian reserve. In some cases, donor embryos and embryos obtained by fertilizing donor oocytes with the husband's sperm contribute to the implantation of their own embryos of low quality. The data obtained require further research and analysis.
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E. B. Rudakova1, Doctor of Medical Sciences, Professor E. A. Fedorova I. V. Sergeeva
GBUZ MO MOPC, Balashikha
1 Contact information
Possibilities for improving the effectiveness of IVF and PE in patients of advanced reproductive age / E. B. Rudakova, E. A. Fedorova, I. V. Sergeeva
For citation: Attending physician No. 12/2017; Issue page numbers: 11-16
Tags: infertility, pregnancy, late reproductive age
Stimulation of superovulation
In order for the likelihood of pregnancy to be higher after one IVF attempt, after embryo transfer, it is necessary to obtain several eggs suitable for fertilization. For this purpose, before the procedure, the so-called stimulation of superovulation is carried out, when the woman is prescribed medications that cause the simultaneous maturation of several follicles. Various drugs can be used to stimulate superovulation. Before stimulation begins, the doctor discusses with you the most appropriate treatment option, selects medications, and determines the sequence of their use, which is called the “stimulation protocol.”
Drugs to stimulate superovulation
Preparations containing follicle-stimulating hormone Follicle-stimulating hormone (FSH) is responsible for the maturation of follicles, therefore, when stimulating superovulation, drugs containing FSH are used. Recombinant drugs are now considered the most effective. They increase the pregnancy rate and reduce treatment costs. One such recombinant FSH is the drug Puregon, created through genetic engineering. Nowadays, for maximum convenience of women, the Puregon Pen injector pen is used. The Puregon Pen injector pen is intended for self-administration of Puregon subcutaneously by patients. The pen is designed for reusable use using a cartridge with a ready-made Puregon solution.
Puregon-Pen reduces the pain of manipulation thanks to microneedling - this is a new method of administering FSH - Puregon, which provides the following advantages:
- maximum accuracy of administration of the dose of Puregon prescribed by the doctor,
- maximum possibilities for dose adjustment based on the individual characteristics of the patient,
- maximum ease of use,
- reduce additional stress associated with the treatment process itself, and therefore your confidence increases.
Drugs that suppress the production of the pituitary gland's own hormones (hormone agonists, antagonists) To prevent a woman's own pituitary gland hormones from interfering with the stimulation of superovulation, their production is blocked by antagonists. Orgalutran is a new antagonist that allows you to instantly block the pituitary gland and then quickly restore its function, which reduces the duration of treatment by almost half compared to traditional drugs (agonists). Agonists (triptorelin, goserelin, leuprorelin, buserelin) require fairly long-term administration. They need to be administered daily for 20–30 days, or once, but in a large dose, which dissolves in about a month.
Preparations containing human chorionic gonadotropin (hCG) Follicular puncture is carried out 36 hours after the injection of hCG, which initiates ovulation of mature follicles. The use of hCG allows you to obtain a mature egg ready for fertilization. One of the drugs containing hCG is Pregnil.
Possible negative consequences
Despite all their effectiveness, IVF and ovarian stimulation, as one of the stages of in vitro fertilization, can have negative consequences.
Considering that hormonal medications are used for stimulation, a woman may develop the following negative factors:
- Overweight and Obesity
- Bloating, abdominal pain, diarrhea and nausea
- Soreness and enlargement of the mammary glands
- Fluid accumulation in the chest and abdomen
- Formation of cysts in the ovaries
All these factors can be attributed to the manifestation of ovarian hyperstimulation syndrome (OHSS), without which it is impossible to obtain several eggs ready for fertilization. Before undergoing the procedure, a woman needs to understand that almost any intervention in the body’s hormonal metabolism does not go away without a trace and can be fraught with serious consequences.
OHSS begins to develop when the activity of the ovaries becomes too pronounced, which harms almost all internal systems and organs.
First of all, hyperstimulation affects the ovaries themselves: they increase in size and swelling appears. During a laboratory blood test, you may notice signs of blood thickening. For this reason, it becomes difficult for the kidneys to remove accumulated fluid from the body, which begins to accumulate in various cavities of the body. The functioning of the entire urinary system malfunctions, the functioning of the gastrointestinal tract and respiratory organs is disrupted.
To reduce ovarian hyperstimulation, doctors most often use outpatient treatment, which involves taking medications to thin the blood, a special diet, plenty of fluids, and rest.
Superovulation stimulation protocols
During in vitro fertilization, different types of protocols are used. It should be remembered that there are no strict treatment regimens; individual variations are possible for each of the protocols below.
"Clean Protocol"
Some women use stimulation regimens without blocking the pituitary gland. For this purpose, only drugs containing FSH are used, for example Puregon Pan. This scheme is called “pure”. Its disadvantage is the likelihood of premature ovulation (rupture) of the follicle even before puncture, which makes it impossible to obtain eggs. With this protocol, the administration of stimulant drugs begins on the 2nd–3rd day of menstruation and continues for 9–14 days. The daily dose is adjusted by the doctor depending on the ultrasound data, which is usually performed 4-5 times during the entire stimulation period. For the final maturation of the follicles, hCG, for example Pregnil, is injected, and after 35–36 hours the follicles are punctured.
"Long Protocol"
The protocol is called “long” because, as a rule, it begins on the 21st–23rd (rarely from the 2nd–3rd) day of the menstrual cycle preceding stimulation. To block the pituitary gland, only an agonist is taken for the first 5 days from the start of treatment. After blockade of the pituitary gland is achieved, menstruation begins, and from the second to third day from its onset, stimulation is carried out with drugs containing FSH, in the same way as with the “pure” regimen, but together with the continued administration of the agonist.
"Optimal Protocol"
When using the new antagonist Orgalutran, the stimulation protocol is significantly shortened, although a pronounced, easily reversible blockade of the pituitary gland remains. Stimulation begins, as with the “pure” regimen, from 2–3 days of the menstrual cycle by daily administration of a drug containing FSH. Then, from the 5th or 6th day of stimulation, daily injections of Orgalutran are given, but stimulation continues. Thus, the “Optimal Protocol” becomes short and therefore effective. The combination of the new generation drug Puregon with Orgalutran (antagonist) is: - reduction of treatment time; - better tolerance of injections; - proven effectiveness. Thanks to this, the combined use of Puregon with Orgalutran can be called “Two components of hope in the treatment of infertility.”
Treatment in Reproductive
Reproductologists approach each case individually. To select the most suitable stimulation scheme, at the first stage a detailed examination of the woman is carried out. First of all, the ovarian reserve is assessed and a forecast of the ovarian response to stimulation is made. Depending on this, a specific protocol, drug and its starting dose are selected. At the same time, possible complications are prevented. In order to create the best conditions for the development of pregnancy, the optimal number of embryos is implanted. If a couple has genetic diseases, preimplantation diagnostics is performed. All this allows us to provide treatment as effectively and safely as possible.
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We do the injections ourselves
Before you start injections, carefully read the storage conditions of the drugs. Some of them require storage at temperatures close to 0°C. Others can be stored at room temperature. Puregon Pen, Orgalutran, Pregnil are stored at temperatures from 3°C to 25–30°C. Freezing of drugs, as well as direct sunlight, can change their activity.
How to give injections?
Using the Puregon Pen injector pen, patients inject themselves themselves, without additional assistance from medical personnel. It's simple, and most importantly, convenient. If a woman uses drugs that are administered with a syringe, you can seek help either in the treatment room of the clinic, or in the clinic at your place of residence, or involve someone familiar with injection skills. Puregon or Orgalutran are administered subcutaneously, Pregnil - intramuscularly. Injections should be done at one time, for example, in the afternoon, and the environment should be as calm as possible. Drugs must be administered slowly. Each administered dose is of great importance, so errors during administration can significantly affect the outcome of the entire treatment. If you forget to administer the drug, do not administer a double dose to make up for the missed injection, but consult your doctor immediately. Some drugs, for example Pregnil, are available in powder form, with solvent ampoules attached separately. Read the instructions carefully. Drugs can only be dissolved using a sterile syringe. The substance dissolves instantly, without foreign impurities.
Monitoring
During stimulation of superovulation, ultrasound monitoring of the growth of ovarian follicles, as well as the maturation of the endometrium, is carried out. This is necessary to adjust the dose of administered drugs, which can be increased or decreased. It all depends on the condition of these organs. On the one hand, it is necessary to obtain a sufficient number of mature eggs, but on the other hand, excessive stimulation can lead to complications. A follicle with a diameter of 17–20 mm is considered mature, with a thickness of the uterine mucosa (endometrium) greater than 8 mm.
Ultrasound monitoring
Monitoring is done by your healthcare provider, usually on days 2–3 of your menstrual cycle. At the same time, stimulant drugs are prescribed. The next follicular growth study is repeated after approximately 5 days. Further studies are carried out more often, almost daily, until the follicles reach sizes close to ovulatory. The study is carried out with an ultrasound sensor, which is inserted into the vagina. This procedure is painless. Do it safely. To ensure sterility, a disposable condom is placed on the sensor. The thickness of the endometrium is assessed, as well as the number and diameter of follicles, and the doctor decides whether to change the dose of drugs. When certain criteria are reached, usually on the 10th–14th day of the cycle, a decision is made to end stimulation. After this, hCG drugs are prescribed, the exact time of their administration is reported, as well as the date of the upcoming puncture.
What should you do?
If you are scheduled for an ultrasound monitoring day, you should not do any injections in the morning without your doctor's advice. An ultrasound through the vagina is performed with an empty bladder, otherwise the doctor will not be able to see the ovaries on the monitor. You will have to undress as if for a gynecological examination.
Administration of hCG
hCG drugs (Pregnil) are administered for the final maturation of the egg. The doctor will tell you the exact time of administration of the drug, which usually occurs in the evening hours. It is very important to strictly observe the time of drug administration. The route of administration is intramuscular. The rules of administration are the same as those described earlier for intramuscular agents. Check the dose of the drug carefully, as the ampoule may contain 1,500, 5,000 IU (International Units). Sexual intercourse should be stopped. It is very important not to be late, to arrive at the puncture on time, 35–36 hours after the hCG injection. It is advisable to take a robe, slippers, nightgown or long T-shirt with you to the puncture, and bring socks. When you have a puncture, your spouse will need to be present.
How many days does stimulation last for IVF?
The time period is determined by the doctor, based on the woman’s health condition. Therefore, stimulation of ovulation during IVF lasts differently for each patient.
Thus, a short protocol lasting one month provides for stimulation of the ovaries for 10 days. And for women who have been diagnosed with endometriosis, cystic changes on the ovaries, or fibroids, hormonal treatment is indicated for 30-40 days, which involves the use of a long protocol. In some cases, super-long ovarian stimulation is indicated, the duration of which can reach up to six months.
The duration of the protocol and the intensity of taking hormonal drugs directly depends on the health status, age and reproductive characteristics of the woman.
When stimulated, copious clear discharge may appear. There is no need to be afraid of this: usually this indicates good growth of the endometrium. You should be wary if there is itching, pain, a strong unpleasant odor, or if the color of the discharge is greenish. All these symptoms may indicate inflammation, which is completely inappropriate for you right now.
Puncture
Puncture of the ovarian follicles is performed to obtain eggs. During the puncture, the doctor, under ultrasound guidance, empties the follicles through the vagina using a needle connected to a vacuum device. As a rule, the puncture is performed in the morning, strictly on an empty stomach, under intravenous anesthesia. There is no reason to be afraid, this procedure is painless, quick, and the thin needle will not cause any serious damage.
Before puncture
You can’t eat anything the night before, or even drink anything after midnight. You can shave the hair around the vaginal opening. You cannot use decorative cosmetics. Immediately before the puncture, already at the IVF clinic, you need to empty your bladder and put on a clean shirt. If you are allergic to any medications, be sure to notify the anesthesiologist about this.
After the puncture
You will wake up in 5-10 minutes, and 40-60 minutes after the puncture you will be able to get up. The doctor will tell you about the results of the puncture, how many eggs were obtained, and then determine the date of the next visit for embryo transfer. The next procedure is embryo implantation; your doctor will tell you on what day to schedule it. The doctor will also give you prescriptions for the next two weeks aimed at maintaining sufficient levels of pregnancy hormones after embryo transfer (hCG injections or progesterone preparations). It is better to have someone accompany you after the puncture. After the puncture, it is strictly forbidden to drive. If you feel pain in the lower abdomen, you can take a painkiller tablet after consulting your doctor. You can only obtain information about the quality of eggs, sperm, success of fertilization, fragmentation, and number of embryos from your attending physician.
Follicle-stimulating hormone: norm and significance
FSH is produced by the pituitary gland, and its release into the blood has a pulse pattern. Large quantities are periodically released throughout the day. They are approximately 1.5-2 times higher than normal. The main role of follitropin is to prepare the follicle for ovulation. After it, FSH helps the formation of progesterone.
For IVF, hormone levels are needed for:
- determining the dose of drugs that contain its synthetic analogues;
- choosing a protocol (long or short);
- assessing the risk of overstimulation.
For the first phase of the cycle, the FSH norm is 1.37-9.91 mIU/ml.
Artificial insemination
When the day of the puncture arrives, the spouse must donate sperm to the laboratory assistant. The sperm is cleaned of excess plasma and prepared for fertilization, checking the quantity, quality, and motility of sperm. The follicular fluid filled with eggs obtained after puncture of the ovaries is examined under a microscope, the eggs are found, they are selected and washed. Each egg is carefully placed in a separate well in a special cup filled with a nutrient medium. Cups containing sperm are always signed immediately. Then, if there are enough sperm and they are motile, some of the sperm is added to the eggs, after which the incubator is left for approximately 12 hours. The sperm themselves must swim to the eggs and fertilize them. Then they check whether fertilization has occurred. Fertilized eggs, or rather embryos, continue to be cultivated for 2 to 5 days.
ICSI
If there are too few sperm, then the ICSI procedure is performed, that is, the injection of a single sperm using a microneedle. Under the control of a microscope, using micromanipulators, the embryologist selects only high-quality sperm and injects them into the egg.
Embryo transfer
When the embryo will be implanted and on what day to schedule the embryo transfer procedure is determined by the doctor. As a rule, this occurs 2–5 days after the puncture. Embryos can be transferred both at the stage of several cells - blastomeres, and at a later stage - blastocysts. The embryo transfer procedure is painless, although slight discomfort is sometimes possible. Speculums are inserted into the vagina, and a flexible catheter is inserted into the cervical canal. Embryos are transferred through this catheter, the number of which is determined by the doctor. It is usually recommended to transfer two embryos, since transferring a larger number is undesirable due to the risk of developing multiple pregnancies. After embryo transfer, the remaining high-quality embryos can be frozen so that they can be used in subsequent attempts.
What should you do when transferring embryos?
During insertion of the catheter, try to relax as much as possible without straining your lower abdomen. Try to be positive. After embryo transfer, you can remain horizontal for some time. It is better to return home with an escort. At home you should also relax and try to distract yourself from obsessive worries.
What to do next?
At this stage - after embryo transfer - the program ends. If there are no complications, the embryo has settled in the uterus and is developing successfully, then you will not be hospitalized. But if you wish, after embryo transfer, you can apply for a hospital stay. The doctor gives clear recommendations on further supportive hormonal treatment, which must be strictly followed. You may be prescribed drugs for hormonal support of pregnancy - progesterone or hCG. Try to spare yourself physically and psychologically in the first weeks after embryo transfer. Try to drink more. After embryo transfer, it is advisable to measure body weight, monitor urination, abdominal volume, and pulse rate. If you have any concerns, please contact the clinic immediately. There you will be issued a sick leave certificate for 10–14 days. If pregnancy occurs after embryo transfer, sick leave can be issued by the antenatal clinic at the place of residence.
Pregnancy - yes or no?
Whether pregnancy has occurred or not will be known no earlier than the 14th day after embryo transfer. Do not try to independently determine pregnancy using tests until this moment, since at this stage the embryo cannot yet produce sufficient amounts of the hCG hormone. The answer may also be incorrect due to the use of certain hormonal medications. In addition, rapid test strips often give false results. Two weeks after embryo transfer, go for a blood test for the beta subunit of hCG, which is an indicator of pregnancy. If the test result is positive, it means pregnancy has occurred. Almost every one and a half to two days the amount of hCG will double. Pregnancy after embryo transfer, determined by hCG, is called “biochemical pregnancy”. She still needs ultrasound confirmation, which allows you to see the fertilized egg only starting from the 3rd week after embryo transfer. Therefore, after embryo transfer, you will need to come for an ultrasound diagnosis of pregnancy. If pregnancy occurs, you should be under constant supervision of obstetricians and gynecologists, since after embryo transfer you still have to carry a pregnancy that was achieved in such a difficult way. If you experience pain, bleeding or other worrying symptoms, contact your doctor immediately. The appearance of menstruation, a negative test result, and the absence of a fertilized egg according to ultrasound data indicate that pregnancy did not occur after embryo transfer. However, a negative result does not mean that the IVF method was ineffective. Subsequent attempts may be successful. As already mentioned, the probability of pregnancy after embryo transfer per attempt ranges from 20 to 30%, and with each subsequent attempt, the total chances of becoming pregnant increase over the course of a year of treatment to 90%. You can leave an interval of about 2 months between attempts. If you are unable to visit the center to diagnose pregnancy, then determination of hCG in the blood after embryo transfer and ultrasound can be carried out in clinics at your place of residence. But in any case, please inform your doctor at the IVF center about the diagnostic results and discuss further actions.
How to prepare
Both women and men need to undergo tests before IVF (if donor sperm is used in the protocol, then only for the woman). The patient is prescribed urine, blood tests (for group and Rh, general, biochemistry, coagulogram, TORCH infections, thyroid and sex hormones), gynecological smears, culture, colposcopy, ultrasound of the thyroid and mammary glands, pelvic organs, according to indications the doctor may refer for hysteroscopy, laparoscopy. You need to have a fluorogram, an ECG, and a therapist’s conclusion about admission to the procedure.
A month or two before entering the protocol, hormonal medications may be prescribed. This will allow the ovaries to rest before stimulation and give a good response to the medications. Recommended diet: more protein foods and clean water, less fast food, legumes, bread (to prevent gas formation). It is important to give up cigarettes and alcohol; bad habits negatively affect the quality and quantity of oocytes.
The patient undergoes a less extensive list of tests for IVF: general blood, urine, biochemistry, TORCH infections. You also need the results of urological smears, and most importantly, a spermogram (if indicated, MAR test). A couple of months before the protocol, it is recommended to give up smoking, alcohol, visiting the sauna and steam bath, wearing tight underwear and using heated seats in the car. All this can significantly deteriorate the quality of sperm.
Possible complications
Ovarian hyperstimulation
As a result of stimulation of the ovaries after puncture, many so-called corpora lutea are formed at the site of the follicles. Some women do not tolerate excess hormones produced by the corpus luteum. In approximately 10% of cases, a mild form of hyperstimulation syndrome develops. This is indicated by pain in the lower abdomen, nausea, and abdominal enlargement. In more serious cases, weakness, decreased urine output, and severe bloating are observed. In rare, severe forms, breathing may become difficult and blood pressure may drop. Treatment for hyperstimulation syndrome usually involves drinking plenty of fluids and taking special medications, which can sometimes be administered intravenously. For mild forms of hyperstimulation, you can stay at home, but be sure to keep your doctor informed of your condition. More severe disease requires hospitalization.
Multiple pregnancy
To increase the likelihood of pregnancy using the IVF method, several embryos (no more than three) are usually transferred into a woman's uterus. Sometimes, after embryo transfer, this can lead to the development of multiple pregnancies. If more than two fetuses develop in the uterus, then carrying such a pregnancy can be quite difficult. There are methods to stop the development of one embryo without affecting the others. This operation is called fetal reduction and is performed under ultrasound guidance. Usually, after embryo transfer, two embryos are left. The likelihood of successfully carrying a pregnancy to term after embryo reduction is higher than if you leave triplets.
Ectopic pregnancy
If, after embryo transfer, weakness, dizziness, early signs of pregnancy, vague or sharp pain appear, then perhaps this is an ectopic pregnancy, in which the fetus develops not in the uterus, but outside it. Seek immediate medical attention as this condition is life-threatening as a ruptured pipe can cause severe bleeding. Ectopic pregnancy is usually treated with gentle laparoscopic surgery. If you experience any of the symptoms listed above, contact your doctor immediately. Write down the clinic's phone number, as well as the doctor's name. Also find out emergency phone numbers. By following all the doctor’s recommendations, you will reduce the risk of complications and at the same time the chances of a happy conception.
Old methods of progesterone support after embryo transfer
Maintenance therapy in the recent past has been quite aggressive despite the fact that the first IVFs were carried out for a long period of time without any hormonal support.
Since follicles are harvested during IVF, the development of corpora lutea is not observed. But the maturation of too many follicles and luteinization of those that were not taken for IVF leads to too high levels of steroid hormones, in particular progesterone, which automatically suppresses the production of luteinizing hormone by the pituitary gland. This, on the one hand, leads to premature luteinization of the follicles, on the other hand, it suppresses the production of progesterone.
However, in the 1990s, women after IVF began to be given oil solutions of progesterone for up to 16 weeks. These were painful injections, and they required women to patiently go to medical institutions to receive hormones, sometimes twice a day. Tablet forms of progesterone turned out to be completely ineffective.
When there was a greater understanding of the role of progesterone in the corpus luteum, maintenance therapy began to be used for no more than 8 weeks, switching to vaginal forms of progesterone administration. The combination of injections with vaginal forms of progesterone has been used very rarely.
Then hormonal therapy was recommended until a stable increase in hCG, which was observed in the 5th week of pregnancy, or an embryo with a heartbeat appeared on ultrasound, which could be seen in the 6th week.
