Uticaj endometrioze na ishod vantelesne oplodnje

Endometriosis is a frequent gynecological disease most often diagnosed in women during\nthe reproductive years. It has been estimated that endometriosis occurs in roughly 10–15% of\ngeneral population,and in women with infertility up to 40%.\nEndometriosis is one of the biggest challenges for gynecologists who deal with the\nproblem of infertility. Mechanism of infertility occurence due to endometriosis is still\nunknown. Many factors can demonstrate the connection between infertility and\nendometriosis. Using the method of in-vitro fertilization (IVF), it is possible to influence\nsome of these factors in order to improve reproductive function. However, what still is the\nissue of in-vitro fertilization program is a response to ovarian stimulation of patients with\nendometriosis. A number of controversial conclusions can be made when going through the\nliterature on this topic. In the modern treatment of endometriosis, laparoscopic surgery is the\nfirst line treatment and is considered the "gold standard" method of treating female infertility.\nThe fact is that a large number of younger patients (40-50%) conceive in the first two years\nafter a laparoscopic procedure done correctly by an experienced gynecologist. So there is still\nmore than 50% of patients to become candidates for in-vitro fertilization, as a\ncomplementary, rather than competing method of treating marital infertility.\nEndometriosis in IVF treatment is a serious problem, both for gynecologists in order to\nobtain a greater number of egg cells, and for embryologists in order to obtain a greater\nnumber of high-quality embryos. Modern literature is facing a problem of reduced ovarian\nresponse in women operated on for endometriosis, especially in those where there is a\nrecurrence. There is a divergence in the opinion of the authors, and various studies attempt to\npoint out the best route. Literature reports different approaches to patients with endometriosis\nwho enter the IVF program, in relation to age, size of the endometrioma, endometriosis\nstages and approach to recurrence of endometriosis. The data are controversial, and so far\nthere are no major randomized trials that clearly indicate the impact of endometriosis on the\noutcome of the IVF and which would form protocols approach to patients with endometriosis\nwho concieve through IVF program.\nTherefore, the aim of our study was:\n1. To examine ovarian reserve in patients operated on for endometriosis, prior to\nentering the IVF program.\n2. Assessment of ovarian response to stimulation in the IVF procedure in patients\noperated on for endometriosis.\n3. Evaluation of IVF outcome (rates of clinical pregnancy, abortion and childbirth) in\npatients operated on for endometriosis.\n4. The impact of (I-IV) endometriosis stage on the IVF course and outcome.\n5. The impact of endometriosis recurrence on ovarian reserve, ovarian response, as well\nas on the course and outcome of the IVF.\n6. Examine what gives higher success rate of IVF: a re-operation of endometriosis\nbefore entering the IVF program or entering into the IVF program with recurrence of\nendometriosis.\n7. Establishment of protocols for assessment of the patients with endometriosis who are\nin the process of IVF.\nThe study was conducted as a prospective-retrospective study at the Department of\nGynecology and Obstetrics, Clinical Center Nish, and the Institute of Human Reproduction,\nDepartment of Gynecology and Obstetrics, Clinical Center Vojvodina, in the period from\n2009. to 2012. Prospective part of the study included monitoring of the patients in the\nprocess of in-vitro fertilization (IVF), and the retrospective section applies to diagnostic\nprocedures and surgeries before entering patients in IVF process. The study included 235\npatients who had undergone the IVF program. The study group included 78 patients with\nendometriosis as a cause of marital infertility, and the control group of 157 patients with tubal\ncause of marital infertility. Certain patients underwent more than one cycle at the same clinic.\nFor other patients, the data of previous IVF attempts, were obtained from the discharge lists\nfrom other IVF centers. After satisfying the criteria for inclusion and exclusion from the\nstudy, in all patients was observed 21defined parameter in the IVF procedure: Basal FSH,\npatient age, body mass index, smoking, previous pregnancy, length of infertility in age,\nstimulation protocol, number of ampoules used for stimulation, length of stimulation, number\nof follicles larger than 15 mm, number of aspirated egg cells, number of obtained embryos,\nnumber of transferred embryos, overall pregnancy rate per embryo transfer (ET), biochemical\npregnancy rate per embryo transfer, clinical pregnancy rate per embryo transfer, the rate of\nabortion, multiple pregnancy rate, birth rate per ET, the rate of interrupted IVF cycle and the\nrate of hyperstimulation. All the parameters in the study group were monitored and compared\nto the stage and recurrence of endometriosis. In relation to the stage, patients were divided\ninto two subgroups – I group included patients with I and II stage of endometriosis, II group\nincluded patients with III and IV stage of endometriosis. All these parameters used in\nresearch were compared between the two groups and compared with the control group. In\nrelation to recurrence of endometriosis, the examined group of patients was divided into three\nsubgroups: the first group consisted of patients who had undergone one surgical procedure\nand showed no signs of endometriosis at the moment of involvement in IVF process; the\nsecond group consisted of patients who had undergone one surgical procedure but had\nrecurrence of endometriosis at the moment of involvement in IVF process, and the third\ngroup consisted of patients who had undergone two or more surgical procedures and showed\nno signs of endometriosis at the moment of involvement in IVF process. All parameters were\ncompared among the groups and with the control group.\nAfter the results had been examined and compared to current literature data and past studies\nin the field, the following conclusions were made:\n Presence of endometriosis in the IVF procedure does not affect the quality of embryo,\nor the rate of fertilization, implantation, clinical pregnancies and labors. However,\npresence of endometriosis affects the number of oocytes, so these patients need more\nampoules of gonadotropins in the process of stimulation, which increases the cost of\ntreatment to achieve pregnancy. The benefit of IVF procedure for patients with\nendometriosis lies partly in controlled ovarian hyperstimulation and achieving greater\nnumber of oocytes, which enables better choice of quality oocytes and thus a better\nfertilization. Likewise, the choice of sufficient number of quality embryos for transfer\ncompensates for the disrupted implantation. The results add to benefit of using GnRH\nanalogues. Ideal model for this research would be IVF procedure with donation of\noocytes, where the quality of oocytes and receptiveness of endometrium before and\nafter GnRH analogues treatment would be examined.\n Patients with III and IV stage of endometriosis have a reduced ovarian reserve,\nweaker response of ovarium to stimulation, a high percentage of cancelled cycles and\nlow rate of clinical pregnancies and deliveries, compared to patients with I and II\nstage of endometriosis. Despite a worse outcome of IVF, compared to patients with\nminimum and mild endometriosis and patients with tubal factor infertility, 31% of\nclinical pregnancies and almost 21% of deliveries of these patients is an excellent rate,\nmaking IVF still the most effective type of treatment that should be suggested to\ninfertile patients with this problem, considering their very low rate of spontaneous\npregnancies.\n Surgical treatment of patients with endometriosis before entering IVF procedure still\nremains controversial. Results of the study show that laparoscopic excision of\nendometrium, is associated with permanent quantitative damage of ovarian reserve.\nThis damage is, however, at least partly present even before surgery and caused by the\nvery disease. Likewise, contrary to patients with decreased ovarian reserve due to age\nor early declining of ovarian function, patients with endometriosis who have\nundergone a surgical treatment, the quality of embryos and the rate of fertilization and\nimplantation are not undermined. They even have the same rate of clinical\npregnancies and deliveries as the patients with tubal infertility. Correlation of surgery\nand lower ovarian response in the process of gonadotropine stimulation should always\nbe considered when patients with endometriosis enter the IVF procedure. Surgical\nexpertise, extension of disease (especially when it comes to bilateral endometrioma),\nprevious ovarian interventions; determine the effect of the surgery on the ovarian\nreserve.\n In case of recurrent endometriosis, new operation worsens the IVF outcome and\nshould be avoided. Except in case of excruciating pain and suspected ovarian masses,\nwhen a patient with recurrent endometriosis should immediately be involved in IVF\nprocedure without new surgery.\n An algorithm of approach to patients with endometriosis and infertility problem has\nbeen suggested. Patients with infertility problem and suspected endometriosis should\nimmediately be sent to diagnostic and therapeutic laparoscopy. If after the surgery\nendometriosis is qualified as histopathological, patient should undergo GnRH\nanalogue therapy and should be offered IVF as an optional treatment. Patients with\ninfertility problem, who have undergone a surgical procedure for endometriosis and\nhave recurrent endometriosis, should immediately be offered IVF with a possible\ntreatment with GnRH analogues for a period of three months