{"paper_id":"24304c8c-bd80-4c2c-ad39-dedb12a441d2","body_text":"Submit Manuscript | http://medcraveonline.com\nAbbreviations: PCOS, polycystic ovary syndrome; LOD, \nlaparoscopic ovarian drilling; AMH, anti mullerian hormone; LH, \nlutenizing hormone; ESHRE, european society of human reproduction \nand embryology; ASRM, American society for reproductive medicine; \nROC, receiver-operating characteristic; BMI, body mass index\nIntroduction\nPolycystic ovary syndrome (PCOS) is one of the most common \nendocrine disorders and the leading cause of infertility in women of \nreproductive age.1 The first line of infertility treatment is clomiphene \ncitrate, the second line includes gonadotrophins or laparoscopic \novarian drilling (LOD) and the third is IVF.2 The mechanism of action \nof LOD is not fully understood and therefore it is not exactly clear \nwhy some PCOS patients do not respond to this treatment.3 The aim of \nthis study was to assess the correlation between patients’ demographic \ndata and hormonal profile and poor ovarian response to LOD.\nMaterials and methods\nA prospective Observational study was designed taking 145 \nprimary infertility, clomiphene resistant patients, admitted to the \nDepartment of Obstetrics and Gynecology, Menoufia University \nhospital, Menoufia, Egypt in the period between October 2008 to \nMarch 2011.\nThe respective approvals of the review board and the ethics \ncommittee of the Menoufia Faculty of medicine were obtained \nbefore commencing the study. The study protocol and its benefits \nand complications were explained to all participants, and all recruited \npatients completed and signed the ‘informed consent’ form. The \nassumed total sample size of the study was actually calculated \naccording to a proposed type I error of 5% with an expected difference \nbetween rates of spontaneous ovulation of 50-90%. Type II error \nwas proposed to be 20% (β=20%) hence the power was set at (1-β, \n80%). Accordingly, 120 patients were needed after adding a 10% for \npossible drop out of cases. \nIncluded patients with PCOS were diagnosed according to the \nrevised European Society of Human Reproduction and Embryology \n(ESHRE) and American Society for Reproductive Medicine (ASRM) \ncriteria of 2004 which were based on the Rotterdam criteria.4 \nClomiphene citrate resistance was defined as the absence of \ndeveloping follicles after ovarian stimulation with 150 mg clomiphene \ncitrate/day given for five days beginning with the 2nd day of the \nmenstrual cycle. Patients were stimulated with clomiphene for a \nminimum of three and a maximum of six cycles. 5 A normal semen \nanalysis, normal uterine cavity and bilateral tubal patency were the \ncriteria of inclusion.\nPatients with FSH>15mIU/ml, medical disorders such as Diabetes \nMellitus and hypertension, contraindications for laparoscopy, \nEndocrine disorders: hyperprolactinaemia (prolactin≥22ng/dl), \nThyroid disorders, Cushing’s syndrome and Acromegaly, husband \nsemen abnormalities and patients having organic pelvic disease \n(endometriosis, leiomyoma, PID, endometrioma or ovarian cyst) upon \nlaparoscopy were excluded from the study. Patients baseline blood \nsamples were obtained before laparoscopic ovarian drilling (2–3 days \nafter the commencement of spontaneous or progesterone induced \nmenstrual bleeding) to assess serum levels of AMH, LH and prolactin. \nThe second blood sample was obtained in the early follicular phase \n(days 2-3) of the menstrual cycle after 3 months of the operation.\nObstet Gynecol Int J. 2015;3(2):276‒279. 276\n©2015 Abo-Elnasr. This is an open access article distributed under the terms of the Creative Commons Attribution License, which \npermits unrestricted use, distribution, and build upon your work non-commercially.\nCould anti-mullerian hormone be a useful predictor \nof the success of laparoscopic ovarian drilling?\nVolume 3 Issue 2 - 2015\nMohamed Abo-Elnasr1,2 \n1Department of Obstetrics and Gynecology, Menoufia \nUniversity, Egypt\n2Department of Obstetrics and Gynecology, Taibah University, \nSaudi Arabia\nCorrespondence: Mohamed Abo-Elnasr, Department of \nObstetrics and Gynecology, Faculty of Medicine, Menoufia \nUniversity, Menoufia, Egypt, T el 201096999838, \nEmail: \nReceived: October 13, 2015 | Published: November 12, 2015\nAbstract\nAim: to assess the correlation between pre-ovarian drilling patients’ demographic data \nand hormonal profile and subsequent spontaneous ovulation and conception following the \nprocedure.\nMethods: Prospective observational study including 145 primary infertility, clomiphene \nresistant patients with polycystic ovary syndrome, undergoing laparoscopic ovarian drilling \n(LOD). The selected patients were directed to have LOD. Ovulation was diagnosed by serial \nfollow up ultrasonography in the subsequent cycles confirmed by day 21 progesterone. \nAntimullerian hormone (AMH), lutenizing hormone (LH) and prolactin assays were done \nbefore and 3 months after the procedure. Receiver operator curve was used to correlate \nbetween demographic and hormonal data and spontaneous ovulation following the \nprocedure.\nResults: There was a significant reduction of AMH, LH and prolactin after LOD in both \ngroups (P<0.001) but the decrease in post-LOD AMH and prolactin is less pronounced in \nthe non-ovulatory group which is significantly higher than in the ovulatory group (P<0.001). \nThe logistic regression analysis revealed that pre-LOD AMH is highly predictive of non-\novulation at a cut off value of 8.8ng/ml with sensitivity of 77% and specificity of 72% \n(P<0.001). Other demographic and hormonal data was not significant. \nConclusion: AMH could be used as a good predictor of ovarian response to LOD. Larger \ntrials are warranted to confirm or refute this finding.\nKeywords: polycystic ovary syndrome, antimullerian hormone, laparoscopic ovarian \ndrilling\nObstetrics & Gynecology International Journal \nResearch Article\n Open Access\n\n\nCould anti-mullerian hormone be a useful predictor of the success of laparoscopic ovarian drilling?\n277\nCopyright:\n©2015 Abo-Elnasr\nCitation: Abo-Elnasr M. Could anti-mullerian hormone be a useful predictor of the success of laparoscopic ovarian drilling? Obstet Gynecol Int J. \n2015;3(2):276‒279. DOI: 10.15406/ogij.2015.03.00076\nAMH assay was done using a commercial ELISA kits (Immunotech, \nBeckman-coulter UK Ltd, High Wycombe Buckinghamshire UK), \naccording to the manufacturer, the sensitivity of the assay is 0.24ng/\nmL. LH assay was performed using automated microparticles enzyme \nimmunoassay (Abbott Axsyem analyzer, Abbott Diagnostics). Mid-\nluteal serum progesterone was measured via Radioimmunassay \n(Immunotech, Westbrook, ME, USA) and prolactin (Immunotech, \nWestbrook, ME, USA).\nPelvic sonography (Acuson 128XP 10, computed sonography \nsystem, Mountain View, California, USA) was carried out on day \n12-16 for folliculometry before and after the operation. Ovulation is \ndefined as the presence of at least one dominant follicle measuring \n≥18mm. Laparoscopic ovarian drilling (LOD) was performed using \nthree-puncture technique. The laparoscope was introduced through a \nsubumblical incision. After assessment of the pelvic structures and \ntubal patency, an insulated needle connected to a unipolar electro-\ncautery with four to six cautery points 3-4 mm in diameter was created \nin each ovary with a current of 4mA applied through the laparoscopic \ninsulated needle.\nOvulation was diagnosed by serial follow up ultrasonography \nin the subsequent cycle confirmed by day 21 progesterone. If no \nmenses occurred within 6 weeks, withdrawal bleeding was done \nand the patients were followed up for 3 months and considered as \nnon-ovulatory. Patients were categorized into two groups, ovulatory \n(n=98) and non-ovulatory (n=47) groups. Patients in both groups were \nfollowed via regular visits to the outpatient clinic every 2-4 weeks to \nrecord the pregnancy rate.\nOutcome measures\n1. The primary outcome was to assess the utility of patients’ \ndemographic criteria and hormonal profile for the prediction of \npoor ovarian response to LOD. \n2. Secondary outcome was to record the pregnancy rate in the \novulatory group during the subsequent 15 months.\nStatistical analysis \nStatistical analysis was performed using Statistical Package for \nthe Social Sciences Version 16 (IBM Corp., Armonk, NY , USA). \nQuantitative data are expressed as means and standard deviations. Chi-\nsquared test and t-test were used to compare the two groups. p≤0.05 \nwas considered to indicate significance and p≤0.001 was considered \nto indicate strong significance. Receiver-operating characteristic \n(ROC) curve analysis was used to evaluate the prognostic value of \ndemographic and hormonal data. \nResults\nTable 1 displays the patients’ demographic data. No significant \ndifference between the ovulatory and non-ovulatory groups regarding \nage, body mass index (BMI) and duration of infertility. Table 2 reveals \nthe hormonal profile before and three months after LOD. There is a \nsignificant reduction of AMH, LH and prolactin after LOD in both \ngroups (P<0.001). Post-LOD AMH and prolactin are higher in the \nnon-ovulatory group than in the ovulatory group (P<0.001). \nTable 3 shows the logistic regression analysis of patients’ \ncharacteristics and hormonal profile among the participants (total no \n145). Pre-LOD AMH is highly predictive of non-ovulation at a cut \noff value of 8.8ng/ml with sensitivity of 77% and specificity of 72% \n(P<0.001). Table 4 shows the pregnancy rate in the ovulatory group \nover 15 months (82/98). Pregnancy rate within the first 6 months was \n60/82 (74.4%) with 22 women (25.6%) conceived in the subsequent \n6 months. \nT able 1 Patients’ demographic data\n \nOvulatory \ngroup \n(n=98)\nNon-\novulatory \ngroup \n(n=47)\nStudent \nt-test P-value\nAge (in years) 29.7±1.5 29.8±1.4 0.38 >0.05\nBody Mass \nIndex 27.9±2.1 28.4±1.8 1.4 >0.05\nDuration of \nInfertility (in \nyears)\n5.4±0.7 5.2±0.5 1.75 >0.05\nT able 2 Hormonal profile before and after LOD\n Ovulatory \ngroup (n=98)\nNon-ovulatory \ngroup (n=47)\nStudent \nt-test P-value\nAMH\nBefore LOD 14.2±4.7 14.6±4.6 0.48 >0.05\nAfter LOD 8.6±3.2 12.2±3.2 6.43 <0.001\nP<0.001 P<0.05\nLH \nBefore LOD 21.1±4.8 21.7±4.5 0.72 >0.05\nAfter LOD 15.3±3.4 15.8±3.2 0.84 >0.05\nP<0.001 P<0.001\nProlactin \nBefore LOD 28.2±5.1 28.8±4.9 0.67 >0.05\nAfter LOD 8.5±3.7 15.2±6.3 8.04 <0.001\n P<0.001 P<0.001   \nAMH, antimullerian hormone; LH, leutinizing hormone\nT able 3 The logistic regression analysis of patients’ characteristics and \nhormonal profile among the participants (T otal no 145)\n AUC Sensitivity Specificity Cut-off \nvalue P-value\nAge 0.586 63% 69% - >0.05\nBMI 0.658 55% 61% - >0.05\nInfertility \nDuration 0.642 64% 52% - >0.05\nAMH 0.714 77% 72% 8.8ng/ml <0.001\nLH 0.66 61% 69% - >0.05\nProlactin 0.626 58% 62% - >0.05\nBMI, body mass index; AMH, antimullerian hormone; LH, leutinizing hormone\n\nCould anti-mullerian hormone be a useful predictor of the success of laparoscopic ovarian drilling?\n278\nCopyright:\n©2015 Abo-Elnasr\nCitation: Abo-Elnasr M. Could anti-mullerian hormone be a useful predictor of the success of laparoscopic ovarian drilling? Obstet Gynecol Int J. \n2015;3(2):276‒279. DOI: 10.15406/ogij.2015.03.00076\nT able 4 Pregnancy rate (n=82) in the ovulatory group over 15 months (n=98)\n Category\nPregnancy rate \nafter 6 months \n(n=60)\nPregnancy rate \nafter 12 months \n(n=22)\nAge\n<25 years 42 16\n≥25 years 18 6\nBMI\n<25 52 18\n≥25 8 4\nInfertility \nduration\n<5 years 54 20\n≥5 years 6 2\nAMH <8.8 56 21\n≥8.8 4 1\nLH\n<10 19 10\n≥10 41 12\nProlactin\n<10 50 17\n≥10 10 5\nBMI, body mass index; AMH, antimullerian hormone; LH, leutinizing hormone\nDiscussion\nIn this series, 47 patients out of 145 were anovulatory (32.4%) \nwith ovulation reported in 98 patients (77.6%). The reported ovulation \nrate after LOD varies between 50% and 90% in the literature. 6 There \nis some disparity between hormonal improvement and ovulation rate \nfollowing LOD.7\nIn this study, the amount of decrease in post-LOD AMH and \nprolactin is less pronounced in the non-ovulatory group since AMH \nand prolactin levels were significantly higher in the pre-LOD non-\novulatory group than in the ovulatory group. \nGjonness et al. 8 in their study on 17 women showed a transient \nhyperprolactinemia immediately after LOD, they believed that \nthis phenomenon was due to operative stress. Hyperprolactinemia \nas a complication of operation, and/or anesthesia was previously \ndescribed with the peak prolactin levels always occurring during \nsurgery. Prolactin remained elevated in 62.5% when measured 6–10 \nweeks after operation.9–11\nAnother possible explanation of anovulation following LOD is that \nthe amount of ovarian tissue destroyed during LOD is not sufficient \nto produce an effect in some patients. However, others believe that \novarian diathermy works by increasing the sensitivity of the ovaries \nto endogenous FSH, and that only a minimal amount of thermal injury \nis required.3\nIn this study, Pre-LOD AMH is highly predictive of non-ovulation \nat a cut off value of 8.8ng/ml with sensitivity of 77% and specificity of \n72% (P<0.001). On the other hand, other demographic and hormonal \ndata has no significant impact on the ovarian response to LOD.\nA previous smaller study was conducted in UK to measure \ncirculating AMH before laparoscopic ovarian diathermy (LOD) \nto evaluate its prognostic value for an ovulatory response and to \ninvestigate AMH changes after LOD to further explore the effects of \nLOD. This study included anovulatory women with PCOS undergoing \nLOD (n=29) or receiving clomiphene citrate (n=18). Plasma AMH \nconcentrations were measured before and 1 week after treatment. \nFurther measurements of AMH were made at 3-and 6-month follow-\nup. AMH was found to be a useful predictor of no ovulation after \nLOD with area under the curve of 0.804 (P=0.025). Using a cut-off of \n7.7ng/ml, AMH had a sensitivity of 78% and a specificity of 76% in \nthe prediction of no ovulation after LOD.12\nIn our series 82(56.5%) patients get pregnant within 15 months \nin the ovulatory group. Pregnancy rate within the first 6 months was \n60/82 (74.4%) and 22 women (25.6%) conceived in the subsequent 6 \nmonths. Pregnancy rate was higher in women younger than 25 years, \nwith BMI less than 25 and infertility duration less than 5 years. \nMany authors have reported high ovulation (about 80%) and \npregnancy (about 60%) rates following LOD. 13–16 Duleba et al. 17 \nreported that lean PCOS women (BMI <25kg/m 2) achieved higher \nconception rates than overweight women (BMI >25kg/m 2) after \nlaparoscopic wedge resection using a harmonic scalpel in 33 PCOS \npatients.17\nIn our series, ovulatory women with higher LH levels (>10IU/l) \nhave a significantly higher chance of conception than those with \nlower LH levels which is consistent with previous studies. 3,18 Failure \nof LOD in women with relatively high levels of AMH may be due to \nseverity of the PCOS condition in these women. It is possible that the \nextent of follicle destruction by LOD in these women was not enough \nto reduce intra-ovarian AMH to a level consistent with resumption of \novulation.12 Future research should explore the use of dose adjusted \nLOD in relation to the serum levels of AMH and subsequent ovulation \nand pregnancy rates. From the results obtained in this clinical study, \nAMH could be used as a good predictor of ovarian response to LOD. \nLarger trials are warranted to confirm or refute this finding.\nAcknowledgments \nThe author would like to acknowledge the contribution of \nthe residents and nursing staff of the operating room and clinical \npathology department of Menoufia university Hospital. \nConflicts of interest \nThe authors declare there is no conflict of interests.\nReferences\n1. Goldenberg N, Glueck C. Medical therapy in women with polycystic \novarian syndrome before and during pregnancy and lactation. Minerva \nGinecol. 2008;60(1):63–75.\n2. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop \nGroup. Revised 2003 consensus on diagnostic criteria and long- health \nrisks related to polycystic ovary syndrome (PCOS). Hum Reprod . \n2008;23(3):462–477.\n3. Amer SA, Li TC, Ledger WL. Ovulation induction using laparoscopic \novarian drilling in women with polycystic ovarian syndrome: predictors \nof success. Hum Reprod. 2004;19(8):1719–1724.\n4. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop \nGroup. Revised 2003 consensus on diagnostic criteria and long-\nterm health risks related to polycystic ovary syndrome. Fertil Steril . \n2004;81(1):19–25.\n5. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop \nGroup. Consensus on infertility treatment related to polycystic ovary \nsyndrome. Hum Reprod. 2008;23(3):462–477.\n6. Abdel Ghadir A, Khatim MS, Mowafi RS, et al. Ovarian electrocautery \nversus human menopausal gonadotropins and pure follicle stimulatin \n\nCould anti-mullerian hormone be a useful predictor of the success of laparoscopic ovarian drilling?\n279\nCopyright:\n©2015 Abo-Elnasr\nCitation: Abo-Elnasr M. Could anti-mullerian hormone be a useful predictor of the success of laparoscopic ovarian drilling? Obstet Gynecol Int J. \n2015;3(2):276‒279. DOI: 10.15406/ogij.2015.03.00076\nhormone therapy in the treatment of the patients with polycystic ovarian \ndisease. Clin Endocrinol. 1990;33(5):585–592.\n7. Balen AH, Jacobs HS. A prospective study comparing unilateral and \nbilateral laparoscopic ovarian diathermy in women with the polycystic \novary syndrome. Fertil Steril. 1994;62(5):921–925.\n8. Gjonnaess H, Norman. Endocrine effects of ovarian electrocautery \nin patients with polycystic ovarian disease. Br J Obstet Gynaecol . \n1987;94(8):779–783.\n9. Adashi EY , Rebar RW, Ehara Y , et al. 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Long term follow-up of patients with \npolycystic ovarian syndrome after laparoscopic ovarian drilling: clinical \noutcome. Hum Reprod. 2002;17(8):2035–2042.\n15. Mohiuddin S, Bessellink D, Farquhar C. Long-term follow up of women \nwith laparoscopic ovarian diathermy for women with clomiphene-\nresistant polycystic ovarian syndrome. Aust N Z J Obstet Gynaecol . \n2007;47(6):508–511.\n16. Flyckt RL, Goldberg JM. Laparoscopic ovarian drilling for clomiphene-\nresistant polycystic ovary syndrome. Semin Reprod Med. 2011;29(2):138–\n146.\n17. Duleba AJ, Banaszewska B, Spaczynski RZ, et al. Success of laparoscopic \novarian wedge resection is related to obesity, lipid profile, and insulin \nlevels. Fertil Steril. 2003;79(4):1008–1014.\n18. Li TC, Saravelos H, Chow MS, et al. Factors affecting the outcome of \nlaparoscopic ovarian drilling for polycystic ovarian syndrome in women \nwith anovulatory infertility. BJOG. 1998;105(3):338–344.","source_license":"CC0","license_restricted":false}