Hysterosalpingo-foam sonography versus hysterosalpingography during fertility work-up: an economic evaluation alongside a randomized controlled trial.

STUDY QUESTION: What are the costs and effects of tubal patency testing by hysterosalpingo-foam sonography (HyFoSy) compared to hysterosalpingography (HSG) in infertile women during the fertility work-up? SUMMARY ANSWER: During the fertility work-up, clinical management based on the test results of HyFoSy leads to slightly lower, though not statistically significant, live birth rates, at lower costs, compared to management based on HSG results. WHAT IS KNOWN ALREADY: Traditionally, tubal patency testing during the fertility work-up is performed by HSG. The FOAM trial, formally a non-inferiority study, showed that management decisions based on the results of HyFoSy resulted in a comparable live birth rate at 12 months compared to HSG (46% versus 47%; difference -1.2%, 95% CI: -3.4% to 1.5%; P = 0.27). Compared to HSG, HyFoSy is associated with significantly less pain, it lacks ionizing radiation and exposure to iodinated contrast medium. Moreover, HyFoSy can be performed by a gynaecologist during a one-stop fertility work-up. To our knowledge, the costs of both strategies have never been compared. STUDY DESIGN, SIZE, DURATION: We performed an economic evaluation alongside the FOAM trial, a randomized multicenter study conducted in the Netherlands. Participating infertile women underwent, both HyFoSy and HSG, in a randomized order. The results of both tests were compared and women with discordant test results were randomly allocated to management based on the results of one of the tests. The follow-up period was twelve months. PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied 1160 infertile women (18-41 years) scheduled for tubal patency testing. The primary outcome was ongoing pregnancy leading to live birth. The economic evaluation compared costs and effects of management based on either test within 12 months. We calculated incremental cost-effectiveness ratios (ICERs): the difference in total costs and chance of live birth. Data were analyzed using the intention to treat principle. MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, 1026 of the 1160 women underwent both tubal tests and had data available: 747 women with concordant results (48% live births), 136 with inconclusive results (40% live births), and 143 with discordant results (41% had a live birth after management based on HyFoSy results versus 49% with live birth after management based on HSG results). When comparing the two strategies-management based on HyfoSy results versus HSG results-the estimated chance of live birth was 46% after HyFoSy versus 47% after HSG (difference -1.2%; 95% CI: -3.4% to 1.5%). For the procedures itself, HyFoSy cost €136 and HSG €280. When costs of additional fertility treatments were incorporated, the mean total costs per couple were €3307 for the HyFoSy strategy and €3427 for the HSG strategy (mean difference €-119; 95% CI: €-125 to €-114). So, while HyFoSy led to lower costs per couple, live birth rates were also slightly lower. The ICER was €10 042, meaning that by using HyFoSy instead of HSG we would save €10 042 per each additional live birth lost. LIMITATIONS, REASONS FOR CAUTION: When interpreting the results of this study, it needs to be considered that there was a considerable uncertainty around the ICER, and that the direct fertility enhancing effect of both tubal patency tests was not incorporated as women underwent both tubal patency tests in this study. WIDER IMPLICATION OF THE FINDINGS: Compared to clinical management based on HSG results, management guided by HyFoSy leads to slightly lower live birth rates (though not statistically significant) at lower costs, less pain, without ionizing radiation and iodinated contrast exposure. Further research on the comparison of the direct fertility-enhancing effect of both tubal patency tests is needed. STUDY FUNDING/COMPETING INTEREST(S): FOAM trial was an investigator-initiated study, funded by ZonMw, a Dutch organization for Health Research and Development (project number 837001504). IQ Medical Ventures provided the ExEm®-FOAM kits free of charge. The funders had no role in study design, collection, analysis, and interpretation of the data. K.D. reports travel-and speakers fees from Guerbet and her department received research grants from Guerbet outside the submitted work. H.R.V. received consulting-and travel fee from Ferring. A.M.v.P. reports received consulting fee from DEKRA and fee for an expert meeting from Ferring, both outside the submitted work. C.H.d.K. received travel fee from Merck. F.J.M.B. received a grant from Merck and speakers fee from Besins Healthcare. F.J.M.B. is a member of the advisory board of Merck and Ferring. J.v.D. reported speakers fee from Ferring. J.S. reports a research agreement with Takeda and consultancy for Sanofi on MR of motility outside the submitted work. M.v.W. received a travel grant from Oxford Press in the role of deputy editor for Human Reproduction and participates in a DSMB as independent methodologist in obstetrics studies in which she has no other role. B.W.M. received an investigator grant from NHMRC GNT1176437. B.W.M. reports consultancy for ObsEva, Merck, Guerbet, iGenomix, and Merck KGaA and travel support from Merck KGaA. V.M. received research grants from Guerbet, Merck, and Ferring and travel and speakers fees from Guerbet. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: International Clinical Trials Registry Platform No. NTR4746.

Can hysterosalpingo-foam sonography replace hysterosalpingography as first-choice tubal patency test? A randomized non-inferiority trial.

STUDY QUESTION: Does hysterosalpingo-foam sonography (HyFoSy) lead to similar pregnancy outcomes, compared with hysterosalpingography (HSG), as first-choice tubal patency test in infertile couples? SUMMARY ANSWER: HyFoSy and HSG produce similar findings in a majority of patients and clinical management based on the results of either HyFoSy or HSG, leads to comparable pregnancy outcomes. HyFoSy is experienced as significantly less painful. WHAT IS KNOWN ALREADY: Traditionally, tubal patency testing during fertility work-up is performed by HSG. HyFoSy is an alternative imaging technique lacking ionizing radiation and iodinated contrast medium exposure which is less expensive than HSG. Globally, there is a shift towards the use of office-based diagnostic methods, such as HyFoSy. STUDY DESIGN, SIZE, DURATION: This multicentre, prospective, comparative study with a randomized design was conducted in 26 hospitals in The Netherlands. Participating women underwent both HyFoSy and HSG in randomized order. In case of discordant results, women were randomly allocated to either a management strategy based on HyFoSy or one based on HSG. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included infertile women between 18 and 41 years old who were scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male infertility or a known iodine contrast allergy were excluded. The primary outcome for the comparison of the HyFoSy- and HSG-based strategies was ongoing pregnancy leading to live birth within 12 months after inclusion in an intention-to-treat analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Between May 2015 and January 2019, 1026 women underwent HyFoSy and HSG. HyFoSy was inconclusive in 97 of them (9.5%), HSG was inconclusive in 30 (2.9%) and both were inconclusive in 9 (0.9%). In 747 women (73%) conclusive tests results were concordant. Of the 143/1026 (14%) with discordant results, 105 were randomized to clinical management based on the results of either HyFoSy or HSG. In this group, 22 of the 54 women (41%) allocated to management based on HyFoSy and 25 of 51 women (49%) allocated to management based on HSG had an ongoing pregnancy leading to live birth (Difference -8%; 95% CI: -27% to 10%). In total, clinical management based on the results of HyFoSy was estimated to lead to a live birth in 474 of 1026 women (46%) versus 486 of 1026 (47%) for management based on HSG (Difference -1.2%; 95% CI: -3.4% to 1.5%). Given the pre-defined margin of -2%, statistically significant non-inferiority of HyFoSy relative to HSG could not be demonstrated (P = 0.27). The mean pain score for HyFoSy on the 1-10 Visual Analogue Scale (VAS) was 3.1 (SD 2.2) and the mean VAS pain score for HSG was 5.4 (SD 2.5; P for difference < 0.001). LIMITATIONS, REASONS FOR CAUTION: Since all women underwent both tubal patency tests, no conclusions on a direct therapeutic effect of tubal flushing could be drawn. WIDER IMPLICATIONS OF THE FINDINGS: HyFoSy or HSG produce similar tubal pathology findings in a majority of infertile couples and, where they differ, a difference in findings does not lead to substantial difference in pregnancy outcome, while HyFoSy is associated with significantly less pain. STUDY FUNDING/COMPETING INTEREST(S): The FOAM study was an investigator-initiated study funded by ZonMw, The Netherlands organization for Health Research and Development (project number 837001504). ZonMw funded the whole project. IQ Medical Ventures provided the ExEm-foam® kits free of charge. The funders had no role in study design, collection, analysis and interpretation of the data. K.D. reports travel and speaker fees from Guerbet. F.J.M.B. reports personal fees as a member of the external advisory board for Merck Serono, The Netherlands, and a research support grant from Merck Serono, outside the submitted work. C.B.L. reports speakers' fee from Ferring in the past, and his department receives research grants from Ferring, Merck and Guerbet. J.S. reports a research agreement with Takeda on MR of motility outside the submitted work. M.V.W. reports leading The Netherlands Satellite of the Cochrane Gynaecology and Fertility Group. B.W.J.M. is supported by an NHMRC Investigator grant (GNT1176437). B.W.J.M. reports consultancy for Guerbet and research funding from Merck and Guerbet. V.M. reports non-financial support from IQ medicals ventures, during the conduct of the study; grants and personal fees from Guerbet, outside the submitted work. The other authors do not report conflicts of interest. TRIAL REGISTRATION NUMBER: NTR4746/NL4587 (https://www.trialregister.nl). TRIAL REGISTRATION DATE: 19 August 2014. DATE OF FIRST PATIENT'S ENROLMENT: 7 May 2015.

[A woman with a tumour in her lesser pelvis]. / Een vrouw met een tumor in het kleine bekken.

A 63-year-old postmenopausal woman was referred for a mass on MRI: a well-defined 13 cm hyperechoic mass with high fat content. Exploratory laparotomy revealed normal ovaries and an enlarged uterus; hysterectomy was performed. Histological examination found uterine lipoleiomyoma, a rare benign type of uterine myoma.

The FOAM study: is Hysterosalpingo foam sonography (HyFoSy) a cost-effective alternative for hysterosalpingography (HSG) in assessing tubal patency in subfertile women? Study protocol for a randomized controlled trial.

BACKGROUND: Tubal pathology is a causative factor in 20% of subfertile couples. Traditionally, tubal testing during fertility work-up is performed by hysterosalpingography (HSG). Hysterosalpingo-foam sonography (HyFoSy) is a new technique that is thought to have comparable accuracy as HSG, while it is less expensive and more patient friendly. HyFoSy would be an acceptable alternative for HSG, provided it has similar effectiveness in terms of patient outcomes. METHODS/DESIGN: We aim to compare the effectiveness and costs of management guided by HyFoSy or by HSG. Consenting women will undergo tubal testing by both HyFoSy and HSG in a randomized order during fertility work-up. The study group will consist of 1163 subfertile women between 18 and 41 years old who are scheduled for tubal patency testing during their fertility work-up. Women with anovulatory cycles not responding to ovulation induction, endometriosis, severe male subfertility or a known contrast (iodine) allergy will be excluded. We anticipate that 7 % (N = 82) of the participants will have discordant test results for HyFoSy and HSG. These participants will be randomly allocated to either a management strategy based on HyFoSy or a management strategy based on HSG, resulting in either a diagnostic laparoscopy with chromopertubation or a strategy that assumes tubal patency (intrauterine insemination or expectant management). The primary outcome is ongoing pregnancy leading to live birth within 12 months after randomization. Secondary outcomes are patient pain scores, time to pregnancy, clinical pregnancy, miscarriage rate, multiple pregnancy rate, preterm birth rate and number of additional treatments. Costs will be estimated by counting resource use and calculating unit prices. DISCUSSION: This trial will compare the effectiveness and costs of HyFoSy versus HSG in assessing tubal patency in subfertile women. TRIAL REGISTRATION: Dutch Trial Register (NTR 4746, http://www.trialregister.nl ). Date of registration: 19 August 2014.

Gonadotrophins for ovulation induction in women with polycystic ovarian syndrome.

BACKGROUND: Ovulation induction with follicle stimulating hormone (FSH) is the second-line treatment in women with polycystic ovary syndrome (PCOS) who do not ovulate or conceive on clomiphene citrate (CC). OBJECTIVES: To compare the effectiveness and safety of gonadotrophins as a second-line treatment for ovulation induction in women with CC-resistant PCOS. SEARCH METHODS: We searched the Menstrual Disorders & Subfertility Group's Specialist Register of controlled trials, the Cochrane Central Register of Controlled Trials, MEDLINE (1966 to October 2014), EMBASE (1980 to October 2014), CINAHL (1982 to October 2014), National Research Register and web-based trials databases such as Current Controlled Trials. There was no language restriction. SELECTION CRITERIA: All randomised controlled trials reporting data on comparing clinical outcomes in women with PCOS who did not ovulate or conceive on CC, and undergoing ovulation induction with urinary FSH (uFSH: FSH-P or FSH-HP), HMG/HP-HMG or recombinant FSH. We included trials reporting on ovulation induction followed by intercourse or intrauterine insemination. We excluded studies that used co-treatment with CC, metformin, LH or letrozole. DATA COLLECTION AND ANALYSIS: Three review authors (NW, MN and MvW) independently selected studies for inclusion, assessed study quality and extracted study data. Primary outcomes were live birth rate per woman (effectiveness outcome) and incidence of ovarian hyperstimulation syndrome (OHSS) per woman (safety outcome). Secondary outcomes were clinical pregnancy, miscarriage, multiple pregnancy, total gonadotrophin dose and total duration of stimulation per woman. We combined data using a fixed-effect model to calculate the odds ratio (OR). We summarised the overall quality of evidence for the main outcomes using GRADE criteria. MAIN RESULTS: The review includes 14 trials with 1726 women. Ten trials compared rFSH versus urinary-derived gonadotrophins (three rFSH versus HMG and seven rFSH versus FSH-HP), four trials compared FSH-P with HMG. We found no trials that compared FSH-HP with FSH-P.We found no evidence of a difference in live birth for rFSH versus urinary-derived gonadotrophins (OR 1.26, 95% CI 0.80 to 1.99, 5 trials, 505 women, I² = 0%, low-quality evidence) or clinical pregnancy rate (OR 1.08, 95% CI 0.83 to 1.39, 8 trials, 1330 women, I² = 0, low-quality evidence). This suggests that for the observed average live birth per woman with urinary-derived FSH of 16%, the chance of live birth following rFSH is between 13% and 26%.For the comparison HMG or HP-HMG versus FSH-P there was also no difference in the evidence on live birth rate (OR 1.36, 95% CI 0.58 to 3.18, 3 trials, 138 women, I² = 0%, low-quality evidence). This suggests that for a woman with a live birth rate of 18% with HMG or HP-HMG, the chance of live birth following uFSH is between 9% and 37%.Trial authors used various definitions for OHSS. Pooling the data, we found no evidence of a difference for rFSH versus urinary-derived gonadotrophins (OR 1.52, 95% CI 0.81 to 2.84, 10 trials, 1565 women, I(2) = 0%, very low-quality evidence) and for HMG or HP-HMG versus FSH-P (OR 9.95, 95% CI 0.47 to 210.19, 2 trials, 53 women, I² = 0%, very low-quality evidence). AUTHORS' CONCLUSIONS: In women with PCOS and CC resistance or CC failure, we found no evidence of a difference in live birth and OHSS rates between urinary-derived gonadotrophins and rFSH or HMG/HP-HMG. Evidence for all outcomes was of low or very low quality. We suggest weighing costs and convenience in the decision to use one or the other.

Pregnancy complications and metabolic disease in women with clomiphene citrate-resistant anovulation randomized to receive laparoscopic electrocautery of the ovaries or ovulation induction with gonadotropins: a 10-year follow-up.

OBJECTIVE: To assess long-term effects of laparoscopic electrocautery of the ovaries compared with ovulation induction with gonadotropins in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS) on the incidence of pregnancy complications like gestational diabetes, hypertensive disorders, and metabolic or cardiovascular disease. DESIGN: Long-term follow-up study. SETTING: Twenty-eight hospitals within the Netherlands. PATIENT(S): One hundred sixty-eight CC-resistant women who had participated in a randomized controlled trial between 1998 and 2001 comparing electrocautery and gonadotropins. INTERVENTION(S): Postal questionnaire, search in medical files. MAIN OUTCOME MEASURE(S): Pregnancy complications, metabolic or cardiovascular disease. RESULT(S): Eighty-two percent of follow-up data were obtained. Thirteen of 68 women (19%) allocated to electrocautery, and 14 of 63 women (22%) allocated to gonadotropins had evidence for pregnancy complications (relative risk 0.86; 95% confidence interval 0.43-1.7). At follow-up, 12 of 69 (17%) women allocated to electrocautery, and 13 of 69 (19%) women allocated to gonadotropins had evidence for metabolic or cardiovascular disease (relative risk 0.90; 95% confidence interval 0.39-2.1). The risk of these was modified by body mass index (BMI), but not by female age or treatment allocation. This study is based on questionnaires and data from medical files. In the absence of routine screening, under-reporting in our follow-up study is likely. CONCLUSION(S): Electrocautery in women with CC-resistant PCOS does not affect pregnancy complications or metabolic or cardiovascular disease later in life compared with ovulation induction with gonadotropins.

Term life birth after late abortion of the first twin.

The incidence of multiple pregnancy has increased significantly in recent years as a result of assisted reproductive therapy. The most important complication of these pregnancies remains preterm delivery. We report an extraordinary case of delayed delivery after late abortion of the first twin. Tocolysis successfully prolonged the pregnancy for more than three months, and combined with antibiotics and corticosteroids resulted in a term delivery of a second healthy sibling. A total of 37 reports that describe 145 cases of intentional delayed delivery are available. Delay of delivery may offer significant improvement in survival and outcome for the remaining fetus. Delay of delivery beyond 37 weeks is uncommon with only eight reports. A protocol for the procedure of delayed delivery of the second twin is suggested.

Treatment preferences and trade-offs for ovulation induction in clomiphene citrate-resistant patients with polycystic ovary syndrome.

OBJECTIVE: To investigate patient preferences and trade-offs for laparoscopic electrocautery of the ovaries relative to ovulation induction with recombinant FSH (rFSH) in patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). DESIGN: Assessment of preferences and trade-offs in a randomized controlled trial. SETTING: Academic hospital. PATIENT(S): Thirty-two CC-resistant patients with PCOS who had been randomly assigned to either laparoscopic electrocautery of the ovaries or ovulation induction with rFSH and 32 control patients with PCOS under treatment with CC. INTERVENTION(S): Preference for laparoscopic electrocautery relative to rFSH was established during an interview. Trade-offs between treatment burden and effectiveness were evaluated by varying hypothetical pregnancy rates after laparoscopic electrocautery until patients switched in their initial preference. MAIN OUTCOME MEASURE(S): Preference for laparoscopic electrocautery of the ovaries; trade-off between burden and effectiveness of treatment. RESULT(S): The majority of the patients would prefer electrocautery of the ovaries over ovulation induction with rFSH if both treatment strategies resulted in similar pregnancy rates. However, most patients were willing to trade off their preference for increased effectiveness: the percentage of patients who preferred electrocautery over rFSH sharply declined when the difference in hypothetical pregnancy rates was more than 5% in favor of rFSH. CONCLUSION(S): Patients with polycystic ovary syndrome are well able to express an informed preference for laparoscopic electrocautery of the ovaries or ovulation induction with rFHS. Preferences are guided by features of the respective treatments but seem to be dominated by their effectiveness and safety.

Urofollitropin and ovulation induction.

Anovulation is a common cause of female infertility. Treatment for women with anovulation is aimed at induction of ovulation. Ovulation induction with follicle-stimulating hormone (FSH) is indicated in women with WHO type II anovulation in whom treatment with clomifene citrate (clomifene) has failed. The majority of these women have polycystic ovary syndrome. The major disadvantages of ovulation induction with FSH are the risk of ovarian hyperstimulation syndrome and the risk of higher order multiple pregnancies. To reduce the rate of complications due to multiple follicular development, FSH should be administered using a chronic low-dose protocol with small dose increments. In women with WHO type I anovulation, an exogenous supply of luteinizing hormone (LH) is required to achieve an adequate follicular response to FSH treatment. Thus, ovulation induction with FSH is not the treatment of choice in these women. FSH is a hormone that stimulates follicle growth and oocyte maturation. Endogenous FSH is produced by the pituitary gland and exists as a family of isohormones exhibiting distinct oligosaccharide structures. FSH for exogenous administration is derived from urine or is produced as recombinant FSH. The commercially available FSH products all contain different mixtures of FSH isoforms. To determine the effectiveness of urofollitropin (urinary-derived FSH), a comparison with the other available gonadotropins was made (i.e. recombinant FSH and human menopausal gonadotropin). Urofollitropin and recombinant FSH appear to be equally effective and well tolerated for ovulation induction. Human menopausal gonadotropin is comparably effective to urofollitropin in terms of pregnancy outcomes. It remains unclear whether human menopausal gonadotropins have a higher risk of overstimulation and ovarian hyperstimulation syndrome compared to urofollitropin in women with polycystic ovary syndrome. In practice, recombinant products are more convenient to use but are also more expensive. Therefore, if availability is not an issue but costs are, there is still a place for the use of urofollitropins for ovulation induction.

Predicting ongoing pregnancy following ovulation induction with recombinant FSH in women with polycystic ovary syndrome.

BACKGROUND: Ovulation induction with recombinant FSH (rFSH) is common in women with polycystic ovary syndrome (PCOS) not responding to clomiphene citrate treatment, despite the associated risk of multiple pregnancies. We analysed clinical, ultrasonographic and endocrine parameters during initial screening of women with clomiphene citrate-resistant PCOS as predictors of ongoing pregnancy within 12 months of treatment following ovulation induction with rFSH. METHODS: Eighty-five women were allocated to receive rFSH as part of a multicentre clinical trial. rFSH was administered in a chronic low-dose step-up protocol. The primary end-point was an ongoing pregnancy within 12 months. A logistic model was built using clinical, ultrasonographic and endocrine parameters to predict the response to rFSH treatment, adjusted for the number of cycles performed. RESULTS: In total, 85 women underwent 272 treatment cycles with rFSH, of which 57 women (67%) achieved an ongoing pregnancy. Oligomenorrhoea, shorter duration of infertility and a lower free androgen index (FAI) were associated with higher chances of an ongoing pregnancy, resulting in a predictive model with a modest discriminative power (area under the curve 0.72, 95% confidence interval 0.64-0.79) that allowed us to distinguish between women with a probability of <5% of attaining an ongoing pregnancy and women with a probability of >25% of doing so. CONCLUSION: A model consisting of oligo/amenorrhoea, duration of infertility and FAI level allowed a distinction to be made between women with a poor chance and women with a good chance of achieving an ongoing pregnancy.

Predictors for treatment failure after laparoscopic electrocautery of the ovaries in women with clomiphene citrate resistant polycystic ovary syndrome.

BACKGROUND: Laparoscopic electrocautery has been put forward as the treatment of choice in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). In order to make an informed treatment decision it would be helpful if we could identify women with PCOS with a high probability of treatment failure following electrocautery of the ovaries. METHODS: Eighty-three women with CC-resistant PCOS were allocated to receive laparoscopic electrocautery followed by CC when anovulation persisted as part of a randomized controlled trial. Multivariable logistic regression analyses using clinical, ultrasonographic and endocrinological parameters were performed to predict (i) failure to ovulate within 8 weeks after electrocautery, and (ii) failure to reach an ongoing pregnancy after electrocautery with or without CC. RESULTS: Of the 83 women, 56 (67%) ovulated within 8 weeks after electrocautery. The model for predicting anovulation after electrocautery included LH/FSH rate, year of menarche and glucose level. Women who were younger at menarche, had a lower LH/FSH ratio and a lower glucose level were more likely to have persistent anovulation. The area under the curve was 0.74. After electrocautery and CC, 41 women reached an ongoing pregnancy. No prognostic parameters could be identified to predict failure to reach an ongoing pregnancy after electrocautery followed by CC. CONCLUSIONS: Persistence of anovulation after electrocautery could be predicted and women with a high risk of persisting anovulation could be distinguished. We were, however, not able to predict treatment failure after electrocautery followed by CC.

Using an electrocautery strategy or recombinant follicle stimulating hormone to induce ovulation in polycystic ovary syndrome: randomised controlled trial.

OBJECTIVE: To compare the effectiveness of an electrocautery strategy with ovulation induction using recombinant follicle stimulating hormone in patients with polycystic ovary syndrome. DESIGN: Randomised controlled trial. SETTING: Secondary and tertiary hospitals in the Netherlands. PARTICIPANTS: 168 patients with clomiphene citrate resistant polycystic ovary syndrome: 83 were allocated electrocautery and 85 were allocated recombinant follicle stimulating hormone. INTERVENTION: Laparoscopic electrocautery of the ovaries followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or induction of ovulation with recombinant follicle stimulating hormone. MAIN OUTCOME MEASURE: Ongoing pregnancy within 12 months. RESULTS: . The cumulative rate of ongoing pregnancy after recombinant follicle stimulating hormone was 67%. With only electrocautery it was 34%, which increased to 49% after clomiphene citrate was given. Subsequent recombinant follicle stimulating hormone increased the rate to 67% at 12 months (rate ratio 1.01, 95% confidence interval 0.81 to 1.24). No complications occurred from electrocautery with or without clomiphene citrate. Patients allocated to electrocautery had a significantly lower risk of multiple pregnancy (0.11, 0.01 to 0.86). CONCLUSION: The ongoing pregnancy rate from ovulation induction with laparoscopic electrocautery followed by clomiphene citrate and recombinant follicle stimulating hormone if anovulation persisted, or recombinant follicle stimulating hormone, seems equivalent to ovulation induction with recombinant follicle stimulating hormone, but the former procedure carries a lower risk of multiple pregnancy.