IMPACT OF ENDOMETRIOSIS ON IN VITRO FERTILIZATION OUTCOME

Niš : [S. Z. Pop-Trajković-Dinić]

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Umnoženo za odbranu. Univerzitet u Nišu, Medicinski fakultet, 2013. Bibliografija: listovi 92-110. Biografija: list 111.

Endometriosis is a frequent gynecological disease most often diagnosed in women during the reproductive years. It has been estimated that endometriosis occurs in roughly 10–15% of general population,and in women with infertility up to 40%. Endometriosis is one of the biggest challenges for gynecologists who deal with the problem of infertility. Mechanism of infertility occurence due to endometriosis is still unknown. Many factors can demonstrate the connection between infertility and endometriosis. Using the method of in-vitro fertilization (IVF), it is possible to influence some of these factors in order to improve reproductive function. However, what still is the issue of in-vitro fertilization program is a response to ovarian stimulation of patients with endometriosis. A number of controversial conclusions can be made when going through the literature on this topic. In the modern treatment of endometriosis, laparoscopic surgery is the first line treatment and is considered the "gold standard" method of treating female infertility. The fact is that a large number of younger patients (40-50%) conceive in the first two years after a laparoscopic procedure done correctly by an experienced gynecologist. So there is still more than 50% of patients to become candidates for in-vitro fertilization, as a complementary, rather than competing method of treating marital infertility. Endometriosis in IVF treatment is a serious problem, both for gynecologists in order to obtain a greater number of egg cells, and for embryologists in order to obtain a greater number of high-quality embryos. Modern literature is facing a problem of reduced ovarian response in women operated on for endometriosis, especially in those where there is a recurrence. There is a divergence in the opinion of the authors, and various studies attempt to point out the best route. Literature reports different approaches to patients with endometriosis who enter the IVF program, in relation to age, size of the endometrioma, endometriosis stages and approach to recurrence of endometriosis. The data are controversial, and so far there are no major randomized trials that clearly indicate the impact of endometriosis on the outcome of the IVF and which would form protocols approach to patients with endometriosis who concieve through IVF program. Therefore, the aim of our study was: 1. To examine ovarian reserve in patients operated on for endometriosis, prior to entering the IVF program. 2. Assessment of ovarian response to stimulation in the IVF procedure in patients operated on for endometriosis. 3. Evaluation of IVF outcome (rates of clinical pregnancy, abortion and childbirth) in patients operated on for endometriosis. 4. The impact of (I-IV) endometriosis stage on the IVF course and outcome. 5. The impact of endometriosis recurrence on ovarian reserve, ovarian response, as well as on the course and outcome of the IVF. 6. Examine what gives higher success rate of IVF: a re-operation of endometriosis before entering the IVF program or entering into the IVF program with recurrence of endometriosis. 7. Establishment of protocols for assessment of the patients with endometriosis who are in the process of IVF. The study was conducted as a prospective-retrospective study at the Department of Gynecology and Obstetrics, Clinical Center Nish, and the Institute of Human Reproduction, Department of Gynecology and Obstetrics, Clinical Center Vojvodina, in the period from 2009. to 2012. Prospective part of the study included monitoring of the patients in the process of in-vitro fertilization (IVF), and the retrospective section applies to diagnostic procedures and surgeries before entering patients in IVF process. The study included 235 patients who had undergone the IVF program. The study group included 78 patients with endometriosis as a cause of marital infertility, and the control group of 157 patients with tubal cause of marital infertility. Certain patients underwent more than one cycle at the same clinic. For other patients, the data of previous IVF attempts, were obtained from the discharge lists from other IVF centers. After satisfying the criteria for inclusion and exclusion from the study, in all patients was observed 21defined parameter in the IVF procedure: Basal FSH, patient age, body mass index, smoking, previous pregnancy, length of infertility in age, stimulation protocol, number of ampoules used for stimulation, length of stimulation, number of follicles larger than 15 mm, number of aspirated egg cells, number of obtained embryos, number of transferred embryos, overall pregnancy rate per embryo transfer (ET), biochemical pregnancy rate per embryo transfer, clinical pregnancy rate per embryo transfer, the rate of abortion, multiple pregnancy rate, birth rate per ET, the rate of interrupted IVF cycle and the rate of hyperstimulation. All the parameters in the study group were monitored and compared to the stage and recurrence of endometriosis. In relation to the stage, patients were divided into two subgroups – I group included patients with I and II stage of endometriosis, II group included patients with III and IV stage of endometriosis. All these parameters used in research were compared between the two groups and compared with the control group. In relation to recurrence of endometriosis, the examined group of patients was divided into three subgroups: the first group consisted of patients who had undergone one surgical procedure and showed no signs of endometriosis at the moment of involvement in IVF process; the second group consisted of patients who had undergone one surgical procedure but had recurrence of endometriosis at the moment of involvement in IVF process, and the third group consisted of patients who had undergone two or more surgical procedures and showed no signs of endometriosis at the moment of involvement in IVF process. All parameters were compared among the groups and with the control group. After the results had been examined and compared to current literature data and past studies in the field, the following conclusions were made:  Presence of endometriosis in the IVF procedure does not affect the quality of embryo, or the rate of fertilization, implantation, clinical pregnancies and labors. However, presence of endometriosis affects the number of oocytes, so these patients need more ampoules of gonadotropins in the process of stimulation, which increases the cost of treatment to achieve pregnancy. The benefit of IVF procedure for patients with endometriosis lies partly in controlled ovarian hyperstimulation and achieving greater number of oocytes, which enables better choice of quality oocytes and thus a better fertilization. Likewise, the choice of sufficient number of quality embryos for transfer compensates for the disrupted implantation. The results add to benefit of using GnRH analogues. Ideal model for this research would be IVF procedure with donation of oocytes, where the quality of oocytes and receptiveness of endometrium before and after GnRH analogues treatment would be examined.  Patients with III and IV stage of endometriosis have a reduced ovarian reserve, weaker response of ovarium to stimulation, a high percentage of cancelled cycles and low rate of clinical pregnancies and deliveries, compared to patients with I and II stage of endometriosis. Despite a worse outcome of IVF, compared to patients with minimum and mild endometriosis and patients with tubal factor infertility, 31% of clinical pregnancies and almost 21% of deliveries of these patients is an excellent rate, making IVF still the most effective type of treatment that should be suggested to infertile patients with this problem, considering their very low rate of spontaneous pregnancies.  Surgical treatment of patients with endometriosis before entering IVF procedure still remains controversial. Results of the study show that laparoscopic excision of endometrium, is associated with permanent quantitative damage of ovarian reserve. This damage is, however, at least partly present even before surgery and caused by the very disease. Likewise, contrary to patients with decreased ovarian reserve due to age or early declining of ovarian function, patients with endometriosis who have undergone a surgical treatment, the quality of embryos and the rate of fertilization and implantation are not undermined. They even have the same rate of clinical pregnancies and deliveries as the patients with tubal infertility. Correlation of surgery and lower ovarian response in the process of gonadotropine stimulation should always be considered when patients with endometriosis enter the IVF procedure. Surgical expertise, extension of disease (especially when it comes to bilateral endometrioma), previous ovarian interventions; determine the effect of the surgery on the ovarian reserve.  In case of recurrent endometriosis, new operation worsens the IVF outcome and should be avoided. Except in case of excruciating pain and suspected ovarian masses, when a patient with recurrent endometriosis should immediately be involved in IVF procedure without new surgery.  An algorithm of approach to patients with endometriosis and infertility problem has been suggested. Patients with infertility problem and suspected endometriosis should immediately be sent to diagnostic and therapeutic laparoscopy. If after the surgery endometriosis is qualified as histopathological, patient should undergo GnRH analogue therapy and should be offered IVF as an optional treatment. Patients with infertility problem, who have undergone a surgical procedure for endometriosis and have recurrent endometriosis, should immediately be offered IVF with a possible treatment with GnRH analogues for a period of three months

Materica, endometrioza, infertilitet, vantelesna oplodnja, laparoskopija

endometriosis, infertility, in vitro fertilization, laparoscopic surgery

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