Wh

                       

                       

hat is the

            

                       

e status o

of pol

      

of surgicp

lycystic

cal intervpatients ovarian

  

ventions

syndrom

s for infe

me?

ertility inn

Apollo Medicine 2012 SeptemberVolume 9, Number 3; pp. 202e205 Review Article

What is the status of surgical interventions for infertility in patientsof polycystic ovarian syndrome?

Geeta Chadha

Senioremail:ReceivCopyrihttp://d

ABSTRACT

Anovulation is a very important component of polycystic ovarian syndrome and it is this that majorly contributes toinfertility in these women.Besides lifestyle changes and medical methods for ovulation induction, one still fails to achieve an ideal scenario attimes and that is a single, good quality follicle.Because of high costs of IVF which uses gonadotropins, and also multifetal pregnancies, it may be advisable to widenthe net and use minor surgical methods like ovarian diathermy.

Copyright © 2012, Indraprastha Medical Corporation Ltd. All rights reserved.

Keywords: Infertility, PCOS, Bariatic surgery, Laparotomy

INTRODUCTION

Surgical treatment in the form of ovarian wedge resectionby laparotomy was first proposed for the treatment of infer-tility in women with polycystic ovary syndrome (PCOS) byStein and Leventhal in 1935.1 However, this procedure waslater largely abandoned, despite promising outcomes ofinitial series, owing to the risk of postoperative adhesionsand substantial loss of ovarian tissue, and was supplantedby the use of medical ovulation induction agents such asclomifene citrate and gonadotropins.2

However, surgical approaches to ovulation inductionhave continued to play a part in the management of infer-tility associated with PCOS both in the form of laparo-scopic ovarian diathermy, essentially a less traumaticmodern version of ovarian wedge resection, and bariatricsurgery. Surgical approaches to infertility are largelyrestricted to cases of anovulation, usually associated withPCOS, and include laparoscopic ovarian drilling/diathermy(LOD) and bariatric surgery for morbid obesity andinfertility.

Consultant, Obstetrics & Gynaecology, Indraprastha Apollo Hospitalgeeta_chadha@hotmail.comed: 22.5.2012; Accepted: 2.7.2012; Available online: 7.7.2012ght � 2012, Indraprastha Medical Corporation Ltd. All rights reservedx.doi.org/10.1016/j.apme.2012.07.004

LAPAROSCOPIC OVARIAN DRILLING

LOD, a less invasivemodification of ovarian wedge resection,was first described in women with PCOS by Gjønæss in 1984who reported ovulation and pregnancy rates as 92 and 58%,respectively.3 Since this time, LOD using both electrocautery(diathermy) and laser vaporization has been performed tocreate multiple (four to ten) puncture holes in the ovariancortex and stroma; the mechanism of action is poorly under-stood but is believed to be similar to that of ovarian wedgeresection with destruction of ovarian androgen-producingthecal cells, leading to local (conversionof androgenic intrafol-licular environment to an estrogenic one) and systemic (reduc-tion in serum levels of androgens and luteinizing hormonetogether with an increase in follicle-stimulating hormonelevels) endocrine changes that are thought topromote follicularrecruitment, maturation and subsequent ovulation.4 In a narra-tive review reporting on the efficacy of LOD based predomi-nately on observational studies, the spontaneous ovulationand pregnancy rates ranged from 54 to 76% and 28 to 56%at 6 months, and 33 to 88% and 54 to 70% at 12 months.

s, New Delhi 110076, India.

.

The status of surgical interventions for infertility in patients of polycystic ovarian syndrome Review Article 203

The most current systematic review and meta-analysis ofrandomized controlled trials (RCTs) examining all RCTs ofinfertile clomiphene citrate-resistant (CCR) women withPCOSundergoingLODdid not identify anyRCTs comparingLOD with placebo/no treatment. However, there were fiveRCTs (338 CCR randomized patients) comparing LOD(6e12 months of follow-up) versus gonadotropin ovulationinduction (three to six treatment cycles), and meta-analysisshowed no difference in live-birth rate per patient, ongoingpregnancy rate per patient, ovulation rate per patient, miscar-riage rate per pregnancy or quality of life between the twointerventions, but there was a reduction inmultiple pregnancyrate per ongoing pregnancy (1vs 17%, respectively; odds ratio[OR]: 0.13; 95% CI: 0.03e0.59) with LOD in CCR PCOSpatients. Therewere also less direct costswith LODcomparedwith gonadotropins.4

Therefore, LOD has been recommended by an expertInternational Consensus Group as second-line therapy inCCR PCOS.5 A subsequent RCT, also supporting thisrecommendation, has therapy in CCR PCOS.5 A subse-quent RCT, also supporting this recommendation, hasdemonstrated no difference between LOD and up to sixcycles of clomifene citrate in terms of live birth, pregnancy,ovulation and miscarriage rates in therapy-naive womenwith PCOS.6

Two RCTs with conflicting results have compared met-formin to LOD in CCR PCOS.7,8 The first of the RCTs tobe published compared metformin to LOD in 120 over-weight (BMI 25e30 kg/m2) CCR women with PCOSwith follow-up over 6 months and found no difference inovulation rate per cycle (55 vs 53%; p > 0.05) or clinicalpregnancy rate per patient (72 vs 56%; relative risk [RR]:1.28 with 95% CI: 0.99e1.70 favoring metformin) buta reduced miscarriage rate per pregnancy (15.4 vs 29%;p < 0.05), higher live-birth rate per patient (59 vs 36%;RR: 1.63 with 95% CI: 1.08e2.46) and lower costs (50vs V1050; p < 0.05) with metformin.8,9

The later RCT to be published compared metformin withLOD in 110 CCR PCOS patients with a mean BMI of36 kg/m2 who were also insulin resistant, with follow-upover 6 months or 30 weeks (whichever occurred first). Inthis study, metformin was less efficacious than LOD witha reduced ovulation rate per cycle (33 vs 51%; RR: 2.05with 95% CI: 1.4e2.9; p ¼ 0.001), pregnancy rate per cycle(4 vs 8%; RR: 2.19 with 95% CI: 1.03e4.63; p ¼ 0.03),and cumulative pregnancy rate per patient (20 vs 38%;RR: 2.47 with 95% CI: 1.05e5.81; p ¼ 0.03) in conjunc-tion with a higher proportion of patients who never ovu-lated (33 vs 14%; RR: 2.85 with 95% CI: 1.11e7.29;p ¼ 0.02) but no difference in first trimester miscarriagerate per pregnancy (18 vs 19%; RR: 1.05 with 95% CI:0.16e6.9; p ¼ 0.09).7

The same group of researchers who published the first ofthe RCTs comparing metformin with LOD subsequentlyconducted an RCT comparing metformin combined withclomifene citrate with LOD, and reported a higher ovula-tion rate per cycle (72 vs 56%, respectively; p ¼ 0.023)and lower cost of treatment (119.6 vs US$316.8, respec-tively; p < 0.001) but no difference in cumulative preg-nancy rate (61 vs 62%, respectively; p ¼ 1.0),miscarriage rate per pregnancy (17 vs 13%, respectively;p ¼ 1.0) or cumulative live-birth rate (52 vs 54%, respec-tively; p ¼ 1.0) in 55 randomized CCR PCOS patientswith a mean BMI of 30 kg/m2 (all had a BMI <35 kg/m2) over 6 months follow-up.10

Despite a risk of postoperative adhesions followingLOD,5 a single RCT has shown that a second-look laparo-scopic adhesiolysis performed 3 months following LOD inCCRwomenwith PCOS has no benefit in terms of pregnancyor miscarriage rates per patient over 6 months follow-up.11

In summary, LOD is recommended as a second-linetherapy in CCR PCOS patients and is an alternative togonadotropin therapy with equal efficacy but lower riskof multiple pregnancy and cost. There is conflictingevidence as to whether metformin alone or LOD is morebeneficial in terms of reproductive outcome. Based ona single small RCT with a primary end point of live-birthrate and sample size defined arbitrarily,10 there was noevidence of a difference in pregnancy or live-birth ratebetween 6-months treatment with either clomifene citratecombined with metformin or LOD.

BARIATRIC SURGERY

Bariatric or weight-loss surgery in the general populationresults in approximately 15e30% weight loss that is sus-tained in the long term.12 A Cochrane review of bariatricsurgery in the general population found that such surgeryresulted in greater weight loss than conventional treatmentin obesity (BMI >30 kg/m2) and a reduction in comorbid-ities such as diabetes and hypertension based on three RCTsand three prospective cohort studies.13 However, thisreview did not assess fertility outcomes and reproductiveoutcomes and reported that caseecontrol and cohort studiesshow improved fertility and a reduction in obstetricalcomplications such as gestational diabetes, macrosomiaand hypertensive disorders of pregnancy, but the incidenceof intra-uterine growth restriction appears to be increased.No conclusions could be drawn regarding the risk ofpreterm labor and miscarriage.14 Another systematic reviewof bariatric surgery in the general population assessed.

A recent review on the treatment of obesity in PCOS pub-lished by an expert International Panel of PCOS Researchers

204 Apollo Medicine 2012 September; Vol. 9, No. 3 Chadha

appointed by the Androgen Excess and PCOS Society identi-fied two uncontrolled observational studies inmorbidly obeseand overweight PCOS women who have reported improve-ment in menstrual cyclicity, ovulation and natural concep-tion.15 This same review also reported that while bariatricsurgery is a potential future treatment option for obesePCOS women, the criteria for performing such bariatricsurgery are still largely debatable andmore scientific researchis required. However, a consensus was reached in the BritishFertility Society guidelines that fertility treatment should bedeferred in the general population of women who aremorbidly obese until they have lost weight to below a BMIof 35 kg/m2.16 The results of pregnancies achieved after bari-atric surgery have recently been reviewed.17 The reviewsupports the conclusion that the risk of adverse maternaland neonatal outcome could be reduced in women who aremorbidly obese with PCOS by bariatric surgery before preg-nancy. However, the review also identifies the lack of high-quality information. Further studies are recommended.

SUMMARY

Laparoscopic ovarian drilling

d Laparoscopic ovarian drilling (LOD) is a second-linetherapy in clomifene citrate-resistant (CCR) womenwith PCOS that is equally effective as three to six treat-ment cycles of gonadotropin ovulation induction interms of fertility outcome, but with a lower risk ofmultiple pregnancy and less direct costs.

d There is a conflicting randomized controlled trial (RCT)evidence as to whether metformin alone or LOD is morebeneficial in terms of reproductive outcome.

Bariatric surgery

d There is a lack of published RCTs on bariatric surgery inPCOS and further research, both observational studiesand RCTs, are recommended.

CONFLICTS OF INTEREST

The author has none to declare.

ACKNOWLEDGMENTS

The author would like to acknowledge Medscape, CREI;Women Health Education, Michael F. Costello, MBBS,FRANZCOG, William L. Ledger, MBBS, for the materialpresented here.

REFERENCES

1. Stein IF, Leventhal ML. Amenorrhea associated with bilateralpolycystic ovaries. Am J Obstet Gynecol. 1935;29:181e191.

2. Unlu C, Atabekoglu CS. Surgical treatment in polycysticovary syndrome. Curr Opin Obstet Gynecol. 2006;18(3):286e292.

3. Gjønæss H. Polycystic ovarian syndrome treated by ovarianelectrocautery through the laparoscope. Fertil Steril.1984;41(1):20e25.

4. Farquhar C, Lilford RJ, Marjoribanks J, Vandekerckhove P.Laparoscopic ‘drilling’ by diathermy or laser for ovulationinduction in anovulatory polycystic ovary syndrome.Cochrane Database Syst Rev. 2007;3:CD001122 [Cochranesystematic review of ovarian drilling. A thorough summaryup to 2006].

5. Thessaloniki ESHRE/ASRM-Sponsored PCOS ConsensusWorkshop Group. Consensus on infertility treatment relatedto polycystic ovary syndrome. Hum Reprod. 2008;23(3):462e477.

6. Amer SA, Li TC, Metwally M, Emarh M, Ledger WL.Randomized controlled trial comparing laparoscopic ovariandiathermy with clomiphene citrate as a first-line method ofovulation induction in women with polycystic ovarysyndrome. Hum Reprod. 2009;24(1):219e225.

7. Hamed HO, Hasan AF, Ahmed OG, Ahmed MA. Metforminversus laparoscopic ovarian drilling in clomiphene- andinsulin-resistant women with polycystic ovary syndrome. IntJ Gynaecol Obstet. 2010;108(2):143e147.

8. Palomba S,Orio F Jr, NardoLG, et al.Metformin administrationversus laparoscopic ovarian diathermy in clomiphene citrate-resistant women with polycystic ovary syndrome: a prospectiveparallel randomized double-blind placebo-controlled trial.J Clin Endocrinol Metab. 2004;89(10):4801e4809.

9. Moll E, Van Der Veen F, Van Wely M. The role of metforminin polycystic ovary syndrome: a systematic review. HumReprod Update. 2007;13(6):527e537.

10. Palomba S, Falbo A, Battista L, et al. Laparoscopic ovariandiathermy vs clomiphene citrate plus metformin as second-line strategy for infertile anovulatory patients with polycysticovary syndrome: a randomized controlled trial. Am J ObstetGynecol. 2010;202(6):E571eE578 [Most recent randomizedcontrolled trial of ovarian drilling versus medical treatmentof polycystic ovary syndrome anovulation].

11. Gurgan T, Urman B, Aksu T, Yarali H, Develioglu O,Kisnisci HA. The effect of short-interval laparoscopic lysisof adhesions on pregnancy rates following Nd-YAG laserphotocoagulation of polycystic ovaries. Obstet Gynecol.1992;80(1):45e47.

12. Buchwald H, Williams SE. Bariatric surgery worldwide 2003.Obes Surg. 2004;14(9):1157e1164.

The status of surgical interventions for infertility in patients of polycystic ovarian syndrome Review Article 205

13. Colquitt JL, Picot J, Loveman E, Clegg AJ. Surgery forobesity. Cochrane Database Syst Rev. 2009;2:CD003641[Cochrane systematic review of bariatric surgery. Usefulgeneral knowledge but not focussed on the management ofanovulation].

14. Guelinckx I, Devlieger R, Vansant G. Reproductive outcomeafter bariatric surgery: a critical review. Hum Reprod Update.2009;15(2):189e201 [Up to date review of the use of bariatricsurgery for treatment of obesity-related infertility that is wellreferenced].

15. Moran LJ, Pasquali R, Teede HJ, Hoeger KM, Norman RJ.Treatment of obesity in polycystic ovary syndrome: a positionstatement of the Androgen Excess and Polycystic OvarySyndrome Society. Fertil Steril. 2009;92(6):1966e1982.

16. Balen AH, Anderson RA. Impact of obesity on female repro-ductive health: British fertility society, policy and practiceguidelines. Hum Fertil (Camb). 2007;10(4):195e206.

17. Maggard MA, Yermilov I, Li Z, et al. Pregnancy and fertilityfollowing bariatric surgery: a systematic review. JAMA.2008;300(19):2286e2296.

Apollo hospitals: http://www.apollohospitals.com/Twitter: https://twitter.com/HospitalsApolloYoutube: http://www.youtube.com/apollohospitalsindiaFacebook: http://www.facebook.com/TheApolloHospitalsSlideshare: http://www.slideshare.net/Apollo_HospitalsLinkedin: http://www.linkedin.com/company/apollo-hospitalsBlog:Blog: http://www.letstalkhealth.in/