{"paper_id":"324bdcb7-a44a-4f7f-8ec3-79450ff2f635","body_text":"At present, approximately 20-35% of all patients undergoing  in vitro  fertilization (IVF) are\ndiagnosed with endometriosis ( 1 ,  2 ) among whom\nabout 30-40% suffer from ovarian endometrioma\n( 3 ,  4 ). The impact of ovarian endometrioma on assisted reproductive technologies (ART) results is\na controversial issue. A previous meta-analysis\n( 5 ) has shown reduced pregnancy rates in women\nwith ovarian endometrioma who underwent IVF\ntreatments when compared to patients with other\ninfertility causes. However, other studies have not confirmed this finding ( 6 - 8 ). In addition, some\nstudies have shown that ovarian endometrioma\ncould adversely affect the number of oocytes retrieved ( 7 ,  9 ), oocyte quality, fertilization rate\n( 5 ,  10 ), embryo quality and implantation rate ( 9 ,\n 11 ,  12 ). Kumbak et al. ( 13 ) have also reported\npoor embryo quality in patients with endometriosis; yet, there have been no effect on pregnancy\nrate. Other studies also found no adverse effect\nof ovarian endometrioma on pregnancy success\nrates ( 14 - 16 ).\nDue to these conflicting results, the optimum\nmanagement of ovarian endometrioma in IVF/\nintra cytoplasmic sperm injection (ICSI) cycles is\nnot clear ( 14 ,  17 ). Some authors believe that ovarian endometriomas should be removed before the\nIVF cycle ( 18 ); however, others have shown that\nexcision of an ovarian endometrioma before an\nIVF cycle is likely to lead poor responses to ovarian stimulation and to impact fertility outcomes\n( 19 ,  20 ).\nThe purpose of the present study was to evaluate\nthe effect of ovarian endometriomas on ovarian response and IVF/ ICSI outcomes when compared to\npatients with mild male factor infertility.\n\nThis cohort study was performed at Royan Institute for Reproductive Biomedicine (Tehran, Iran)\nover a 24-months period between March 2005 and\nDecember 2007. We recruited a total of 104 women who were candidates for IVF/ICSI and fresh\nembryo transfers.\nThe study group consisted of 47 infertile women\nwith either unilateral or bilateral ovarian endometrial cysts of less than 3 cm, based upon transvaginal sonographic diagnosis with diffuse low-level\nechoes without neoplastic or acute hemorrhage\nfeatures. Patients had no histories of any ovarian\nsurgeries. All ultrasound tests were performed by\ntwo expert technicians using an EUB 6000 (HI-\nTACHI, Japan) equipped with a 6 MHZ curvilinear color doppler probe. Technicians performed\ntrans-vaginal ultrasounds between days 1 and 8\nof the cycle, before starting ovarian stimulation.\nThe location and dimension of the endometriomas\nwere recorded at this time.\nPatients with endometriomas larger than 3 cm\nunderwent endometriotic cystectomy, via laparoscopic surgery. These patients were not included\nat the study. There was no patient with cystectomies, defined as a laparoscopic surgery applied for\nwomen with small ovarian endometriomas.\nThe control group consisting of 57 patients with\nmild male factor infertility was candidate for ICSI\ntreatment during the same time period as the study\ngroups. Mild male factor infertility was defined as\nthe presence of at least 1 million motile sperm after processing.\nAll patients in both groups had indications for\nIVF/ICSI treatments, without any previous attempts.\nExclusion criteria for both groups were as follows: i. previous history of any systematic disease\nor malignancy, ii. basal follicle-stimulating hormone (FSH) more than 15 mIU/ml, iii. history of\nthree or more unsuccessful IVF attempts, and iv.\novarian endometrioma less than 3 cm.\nThe study was approved by the Ethics Committee of Royan Institute for Reproductive Biomedicine. A written informed consent was obtained\nfrom all individuals before participation.\nStimulation protocol for all patients was according to the standard long protocol. All patients\nunderwent oral contraceptive suppression starting from the 2 nd \nor 3 rd \nday of the menstrual cycle.\nGonadotropin-releasing hormone agonist (GnRH\nagonist) suppression with Busereline (500 µg,\nSuprefact; Aventis Pharma Deutshlan, Frankfurt,\nGermany) was performed via subcutaneous injection starting on the 21 st \nday of the menstrual cycle.\nWe began gonadotropin stimulation 14 days after\nsubcutaneous GnRH agonist injection with daily\ndose of 150 IU of recombinant FSH (Gonal F; Serono, Geneva, Switzerland). The dose and duration\nof FSH treatment were adjusted by monitoring follicular development using ultrasound and estradiol\nlevels. In both groups, gonadotropin stimulation\ncontinued until 2-3 follicles with a mean diameter\nof ≥17 mm were achieved. Then, 10000 IU of human chorionic gonadotropin (hCG; Choriomon;\nIBSA, Lugano, Switzerland) was administered,\nwhile oocyte retrieval was performed 34-36 hours\nlater by a skilled gynecologist. Only normal follicles were punctured at the time of oocyte retrieval.\nDuring the procedure, every effort was made to\navoid puncturing the endometrioma. If endometriomas were accidentally punctured, the procedure was interrupted and resumed after the needled was\nchanged.\nMetaphase II (MII) oocytes were injected using ICSI procedure. Normal fertilization was confirmed when two distinct pronuclei were present\nwithin 16-18 hours following oocyte injection.\nIn our ICSI cycles, cumulus-enclosed oocytes\nwere treated with 0.1% hyaluronidase, and the\ncumulus cells were mechanically removed by\npipetting. Oocyte maturation stage and morphology were assessed under an inverted microscope\n(Olympus, Tokyo, Japan) at ×400 magnification.\nOocytes were classified as MII oocyte (mature oocyte), metaphase I oocyte, or prophase I oocyte.\nGood quality cleaved embryos ( 21 ) were transferred 2-3 days after oocyte retrieval.\nProgesterone supplementation (400 mg twice a\nday; Aburaihan Co., Tehran, Iran) was provided\nat time of oocyte retrieval until the day of β-hCG\nassay. After obtaining a positive pregnancy test result, it was continued until the 10 th \nweek of gesta-\ntion.\nThe initial dose, total dose and days of gonadotropin, endometrium thickness, and concentration\nof estradiol (E 2 ) on the days of hCG injection were\nrecorded. Numbers of retrieved eggs, rate of cleavage, numbers of embryos grades A and B obtained,\nscores of the transferred embryos, as well as rates\nof clinical pregnancy and implantation were calculated.\nPrimary endpoints were ovarian response and\noocyte quality and quantity. The quality of embryos, biochemical, clinical pregnancy and implantation rates were other outcomes of interest.\nWe defined the fertilization rate as the ratio of the\nnumber of embryos formed relative to the number of MII oocytes injected. The maturation rate\nwas the ratio of MII oocytes to the number of total\nretrieved oocytes. Clinical pregnancy was a positive pregnancy test result followed by the presence\nof a gestational sac on trans-vaginal ultrasound, 4\nweeks after transfer. The pregnancy rate in the present study was calculated by dividing the number\nof clinical pregnancies detected by the number of\npatients (clinical pregnancy per patient). The implantation rate was the number of gestational sacs\nvisualized by trans-vaginal pelvic ultrasound per\nembryos transferred. In addition, we compared the\nnormal and involved ovaries in patients with unilateral endometrioma.\nAnalysis was performed using the SPSS (version 13.0; SPSS Inc., Chicago, IL, USA) statistical\nsoftware. Between-group differences of normally\ndistributed continuous variables were assessed\nby student’s t test, whereas the Mann-Whitney U\ntest was used for the abnormal distributed data.\nSignificant differences were evaluated by the chisquare test to compare non-continuous variables.\nIn inter-group comparison, the paired t test analysis and Wilcoxon Signed Ranks test were applied\nfor patients with unilateral endometrioma and for\nnonparametric cases, respectively. Data were expressed as mean ± standard deviation (SD). Statistical significance was considered when p<0.05.\n\nThe baseline characteristics including age, duration of infertility, and basic concentrations of E 2 \nand FSH level were similar between two groups\n( Table 1 ).\nThe mean number of retrieved oocytes in patients\nwith endometrioma and in control group were 6.6\n± 3.74 vs. 10.4 ± 5.25, respectively (p<0.001). As\nseen in table 2, the numbers of MII oocytes were\nsignificantly lower in patients with endometrioma\n(5 ± 3.21) as compared to the control group (8.2\n± 5.4).\nThe thickness of the endometrium, follicle numbers and good quality embryos (grades A or B)\nwere also comparable between the two groups\n(p>0.05). Both groups had similar implantation\nand pregnancy rates ( Table 2 ). However, patients\nwith endometrioma had higher gonadotropin consumption as compared with the control group. We\nhad no severe ovarian hyperstimulation syndrome\n(OHSS) in both groups.\nIn patients with unilateral endometrioma, we\ncompared outcomes between the affected ovary\nand healthy contra lateral ovary. There were no\nsignificant differences in terms of main outcome\nmeasures between the normal and involved ovaries ( Table 3 ).\nComparison of the baseline characteristics between patients with endometrioma and control groups\nData are expressed as mean ± SD, otherwise it is reported.\n*; Median(Min-Max) and Mann-Whitney test is used.\nComparison of ICSI cycles outcomes between the patients with endometrioma and control groups\nData are expressed as mean ± SD. OR; Odds Ratio and *; 95% Confidence Interval for odds ratio.\nComparison of the clinical outcomes between the normal and involved ovaries in the patients with unilateral endometrioma\nData are expressed as mean ± SD, otherwise it is mentioned.\n\nIn the present study, the number of retrieved oocytes and MII oocytes were significantly lower in\nendometrioma patients than the controls; however,\nthe number of good quality embryos (per MII injected oocyte) was comparable in both groups.\nThese results were consistent with previous investigations that found a lower ovarian response to gonadotropin stimulation in patients with endometrioma\n( 13 ,  22 ). Al-Azemi et al. ( 23 ) have reported that ovarian endometrioma led to a decreased response to gonadotropins, as reflected by the smaller number of retrieved oocytes, which was also shown in our study.\nPellicer et al. ( 24 ) have demonstrated that endometriosis caused poor quality oocytes and embryos with decreased ability for implantation. Different mechanisms such as changes in autoimmune\nfactors, cytokines or production of growth factors,\nincreased rate of granulosa cell apoptosis, and decreased steroid levels were considered as negative\nfactors for follicular growth and oocyte maturity in\nthese patients ( 25 ,  26 ).\nAlthough some studies have reported poor\nIVF-embryo transfer (ET) outcomes with endometriosis ( 9 ,  11 ,  12 ), we could not find any negative\nimpact of ovarian endometrioma on clinical pregnancy and implantation rates. Some scholars have also\nshown that the existence of endometrioma did not influence embryo implantation, and have proposed that\nthe detrimental effects were limited to the fertilization\nphase ( 27 ).\nIn patients with unilateral endometrioma, the presence of endometrioma at the time of aspiration did\nnot compromise our ICSI outcomes. This result was\nin accordance with the study of Almog et al. ( 28 ) in\nwhich they found a similar number of antral follicles\nand oocytes retrieved from the affected and healthy\ncontra lateral ovaries. It seems that in women with\nunilateral disease, the contra lateral intact ovary compensated for ovarian function and fertility potential\n( 14 ). In the present study, we did not include patients\nwho had surgery for their endometriosis. Additional\nstudies are required to evaluate the effect of surgery.\n\nDespite the lower response to gonadotropins\nin endometrioma patients, the rates of pregnancy and implantation rates, embryo quality, total\nnumber of embryos transferred per patient and\nfertilization of MII oocytes were not affected\nby the presence of the endometrioma. It seems\nthat endometrial receptivity in two groups was\nsimilar. However, in consideration of the higher\ncancelling rate, the prognosis for patients with\nendometrioma was worse than in patients with\nmale associated infertility.","source_license":"CC0","license_restricted":false}