The effect of laparoscopic ovarian drilling in patients with anovulatory polycystic ovary syndrome and high serum levels of anti-Müllerian hormone.

Female infertility is often associated with anovulatory polycystic ovary syndrome (PCOS), characterized by high serum levels of anti-Müllerian hormone (AMH). Laparoscopic ovarian drilling (LOD) is commonly used to treat PCOS, especially when drug interventions have failed. This study aimed to evaluate the response to LOD intervention in women with PCOS by assessing AMH serum levels and their ability to restore normal physiological menstrual cycle and achieve conception. Seventy-five infertile women (24-41 years old) with body mass index (BMI) ranging from 19.6-35kg/m2 were included in the study. Among them, 57 had primary infertility, and 18 from secondary infertility, with an average duration of 8.6±4.4 years. Baseline levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and AMH were measured, and post-LOD levels of LH and AMH were evaluated. Menstrual cycle regularity was evaluated before and after LOD. Baseline FSH serum level before LOD was 5.2-1.6IU/L. Following LOD, the serum levels of LH and AMH significantly decreased from 14.3±4.1 to 7.8±2.8 IU/L and from 13.7±5.9 to 7.7±3.9 IU/L, respectively (p<0.05). LOD significantly (p<0.05) decreased the menstrual cycles irregularity, such as oligomenorrhea and amenorrhea, from 55 (73.3%) to 22 (29.3%) women and from 2 (2.7%) to 0 (0%) women respectively. Moreover, regular menstrual cycles significantly (p<0.05) increased from 18 (24%) to 53 (70.7%) women. Importantly, 68% of LOD-treated women showed a significant increase in pregnancy rates, with 52.9%, 35.3%, and 11.8% achieving pregnancy within 3, 6, and 9 months after LOD, respectively (p<0.05). Moreover, spontaneous ovulation was observed in 7/75 (9.3%) women within 90 days after LOD, and 71.4% achieved pregnancy. These findings highlight the success of laparoscopic ovarian drilling as an intervention for PCOS, with AMH serving as a reliable test to assess the response to LOD treatment.

Ovarian Drilling: Back to the Future.

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. The complex metabolic dysregulation at the base of this syndrome often renders infertility management challenging. Many pharmacological strategies have been applied for the induction of ovulation with a non-negligible rate of severe complications such as ovarian hyperstimulation syndrome and multiple pregnancies. Ovarian drilling (OD) is currently being adopted as a second-line treatment, to be performed in case of medical therapy. Laparoscopic ovarian drilling (LOD), the contemporary version of ovarian wedge resection, is considered effective for gonadotropins in terms of live birth rates, but without the risks of iatrogenic complications in gonadotropin therapy. Its endocrinal effects are longer lasting and, after the accomplishment of this procedure, ovarian responsiveness to successive ovulation induction agents is enhanced. Traditional LOD, however, is burdened by the potential risks of iatrogenic adhesions and decreased ovarian reserve and, therefore, should only be considered in selected cases. To overcome these limits, novel tailored and mini-invasive approaches, which are still waiting for wide acceptance, have been introduced, although their role is still not well-clarified and none of them have provided enough evidence in terms of efficacy and safety.

Laparoscopic ovarian drilling for ovulation induction in women with anovulatory polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common condition affecting 8% to 13% of reproductive-aged women. In the past clomiphene citrate (CC) used to be the first-line treatment in women with PCOS. Ovulation induction with letrozole should be the first-line treatment according to new guidelines, but the use of letrozole is off-label. Consequently, CC is still commonly used. Approximately 20% of women on CC do not ovulate. Women who are CC-resistant can be treated with gonadotrophins or other medical ovulation-induction agents. These medications are not always successful, can be time-consuming and can cause adverse events like multiple pregnancies and cycle cancellation due to an excessive response. Laparoscopic ovarian drilling (LOD) is a surgical alternative to medical treatment. There are risks associated with surgery, such as complications from anaesthesia, infection, and adhesions. OBJECTIVES: To evaluate the effectiveness and safety of LOD with or without medical ovulation induction compared with medical ovulation induction alone for women with anovulatory polycystic PCOS and CC-resistance. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group (CGFG) trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers up to 8 October 2019, together with reference checking and contact with study authors and experts in the field to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of women with anovulatory PCOS and CC resistance who underwent LOD with or without medical ovulation induction versus medical ovulation induction alone, LOD with assisted reproductive technologies (ART) versus ART, LOD with second-look laparoscopy versus expectant management, or different techniques of LOD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, extracted data and evaluated the quality of the evidence using the GRADE method. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS), ovulation, costs, and quality of life were secondary outcomes. MAIN RESULTS: This updated review includes 38 trials (3326 women). The evidence was very low- to moderate-quality; the main limitations were due to poor reporting of study methods, with downgrading for risks of bias (randomisation and allocation concealment) and lack of blinding. Laparoscopic ovarian drilling with or without medical ovulation induction versus medical ovulation induction alone Pooled results suggest LOD may decrease live birth slightly when compared with medical ovulation induction alone (odds ratio (OR) 0.71, 95% confidence interval (CI) 0.54 to 0.92; 9 studies, 1015 women; I2 = 0%; low-quality evidence). The evidence suggest that if the chance of live birth following medical ovulation induction alone is 42%, the chance following LOD would be between 28% and 40%. The sensitivity analysis restricted to only RCTs with low risk of selection bias suggested there is uncertainty whether there is a difference between the treatments (OR 0.90, 95% CI 0.59 to 1.36; 4 studies, 415 women; I2 = 0%, low-quality evidence). LOD probably reduces multiple pregnancy rates (Peto OR 0.34, 95% CI 0.18 to 0.66; 14 studies, 1161 women; I2 = 2%; moderate-quality evidence). This suggests that if we assume the risk of multiple pregnancy following medical ovulation induction is 5.0%, the risk following LOD would be between 0.9% and 3.4%. Restricting to RCTs that followed women for six months after LOD and six cycles of ovulation induction only, the results for live birth were consistent with the main analysis. There may be little or no difference between the treatments for the likelihood of a clinical pregnancy (OR 0.86, 95% CI 0.72 to 1.03; 21 studies, 2016 women; I2 = 19%; low-quality evidence). There is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage (OR 1.11, 95% CI 0.78 to 1.59; 19 studies, 1909 women; I2 = 0%; low-quality evidence). OHSS was a very rare event. LOD may reduce OHSS (Peto OR 0.25, 95% CI 0.07 to 0.91; 8 studies, 722 women; I2 = 0%; low-quality evidence). Unilateral LOD versus bilateral LOD Due to the small sample size, the quality of evidence is insufficient to justify a conclusion on live birth (OR 0.83, 95% CI 0.24 to 2.78; 1 study, 44 women; very low-quality evidence). There were no data available on multiple pregnancy. The likelihood of a clinical pregnancy is uncertain between the treatments, due to the quality of the evidence and the large heterogeneity between the studies (OR 0.57, 95% CI 0.39 to 0.84; 7 studies, 470 women; I2 = 60%, very low-quality evidence). Due to the small sample size, the quality of evidence is not sufficient to justify a conclusion on miscarriage (OR 1.02, 95% CI 0.31 to 3.33; 2 studies, 131 women; I2 = 0%; very low-quality evidence). Other comparisons Due to lack of evidence and very low-quality data there is uncertainty whether there is a difference for any of the following comparisons: LOD with IVF versus IVF, LOD with second-look laparoscopy versus expectant management, monopolar versus bipolar LOD, and adjusted thermal dose versus fixed thermal dose. AUTHORS' CONCLUSIONS: Laparoscopic ovarian drilling with and without medical ovulation induction may decrease the live birth rate in women with anovulatory PCOS and CC resistance compared with medical ovulation induction alone. But the sensitivity analysis restricted to only RCTs at low risk of selection bias suggests there is uncertainty whether there is a difference between the treatments, due to uncertainty around the estimate. Moderate-quality evidence shows that LOD probably reduces the number of multiple pregnancy. Low-quality evidence suggests that there may be little or no difference between the treatments for the likelihood of a clinical pregnancy, and there is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage. LOD may result in less OHSS. The quality of evidence is insufficient to justify a conclusion on live birth, clinical pregnancy or miscarriage rate for the analysis of unilateral LOD versus bilateral LOD. There were no data available on multiple pregnancy.

Effects of follicular ablation and induced luteolysis on LH and follicular fluid factors during the periovulatory period in mares.

Haemorrhagic anovulatory follicles (HAFs) are the most common pathological anovulatory condition in the mare. To enhance understanding of the physiopathology of HAFs, the aim of the present study was to determine the effects of an induced-follicular wave on LH concentrations and follicular fluid factors relevant to the ovulatory process. Mares were allocated to treatment or control groups (n = 7/group) in a crossed over design during 14 oestrous cycles with a period of one cycle occurring when there were no treatments between the times when treatments were administered. In the treatment group, all antral follicles ≥8 mm were ablated on Day 10 after ovulation followed by administration of a luteolytic dose of PGF2α. All mares of both groups were treated with 1500 IU of hCG when a follicle ≥32 mm was detected (Hour 0), and follicular fluid was aspirated 35 h later. Blood samples were collected every 48 h from Day 10 until Hour 0 from all mares. Follicular fluid was assayed for PGE2, estradiol and progesterone. Plasma was assayed for LH concentrations. A follicular wave followed follicle ablation in the treated mares. Concentrations of LH were greater (P = 0.05) in mares ot the treatment compared with control group. Concentrations of PGE2, estradiol and progesterone in follicular fluid did not differ between groups (P > 0.05). Treatment resulted in an earlier increase in circulating LH, however, there was no effect on concentrations of intra-follicular PGE2, estradiol or progesterone in hCG-stimulated preovulatory follicles.

Operative transvaginal hydrolaparoscopy improve ovulation rate after clomiphene failure in polycystic ovary syndrome.

Aim of our study was to assess the ovulation rate, with mid-luteal progesterone level and ultrasound follicles monitoring, in PCOS CC-resistant patients undergone transvaginal hydrolaparoscopy ovarian drilling. A prospective observational study was carried out in 123 PCOS, infertile, CC-resistant patients who undergone THL ovarian drilling. Each woman was evaluated by hormonal measurement, and ultrasound evaluation during 6 months follow-up. Progesterone serum levels were assessed on days 20-24 of the cycle after surgical treatment. Pg levels >3 ng/mL were considered as ovulation. Ovulation frequency and the highest mean follicular diameters during the monitoring were recorded. 117 patients complete the study, since six patients were lost to follow-up. Mean follicular diameter during ovulation monitoring was 16.37 mm. Ovulation rate at the follow up was 64.1% one month after treatment, 79.5% after three months and 82.9% after six months. 28 patients conceived during follow-up period. Pregnancy rate was 70.1%. Our study has shown that THL ovarian drilling improves ovulation and pregnancy rate in women with CC-resistant PCOS. We believe that this approach should be offered as second-line therapy at all PCOS CC-resistant women who fail the medical methods of ovulation induction.

Drilling: medical indications and surgical technique / Drilling: indicações e técnica

SUMMARY Introduction: anovulation is a major cause of female infertility, and polycystic ovary syndrome (PCOS) is the leading cause of anovulation. While undergoing drug-induced ovulation, women with PCOS usually have a satisfactory response recruiting follicles, but some are unable to recruit follicles or often produce an excessive number of follicles, which can result in ovarian hyper-stimulation syndrome and/or multiple pregnancy. Surgical laparoscopy with ovarian "drilling" may prevent or reduce the need for drug-induced ovulation. Objective: to identify the current indications of laparoscopic ovarian drilling and the best surgical technique. Method: a review of the medical literature based on systematic search in the Medline, Lilacs and Cochrane databases, using as keywords laparoscopy, polycystic ovary syndrome, and drilling. Results: we found 105 articles in the literature, 27 of these highly relevant, describing findings on ovarian drilling. Conclusion: laparoscopic drilling is indicated for patients with polycystic ovary syndrome with ovulatory resistance to the use of clomiphene citrate, body mass index less than 30 kg/m2 and preoperative luteinizing hormone above 10 IU/L. The preferred surgical technique should be the realization of 5 to 10 perforations on the surface of each ovary bilaterally using monopolar energy.

RESUMO Introdução: a anovulação é uma das principais causas de infertilidade feminina, e a síndrome dos ovários policísticos (SOP) é a principal causa de anovulação. As mulheres com SOP, quando submetidas a indução medicamentosa da ovulação, costumam ter resposta satisfatória, recrutando folículos. No entanto, algumas podem não recrutar folículos ou, muitas vezes, têm uma produção excessiva deles, o que pode resultar em síndrome de hiperestímulo ovariano e/ou gravidez múltipla. O tratamento cirúrgico por laparoscopia comdrilling ovariano pode evitar ou reduzir a necessidade de indução da ovulação com medicamentos. Objetivos: identificar as indicações atuais do drilling ovariano laparoscópico e qual a melhor técnica operatória. Método: revisão da literatura médica, por meio de busca sistemática nas bases de dados MEDLINE, LILACS e Cochrane, utilizando as palavras-chave: laparoscopia, síndrome dos ovários micropolicísticos edrilling. Resultados: foram encontrados 105 artigos na literatura, sendo 27 de grande relevância descrevendo achados sobre o drilling ovariano. Conclusão: o drilling laparoscópico está indicado para pacientes com SOP com resistência ovulatória ao uso do citrato de clomifeno, índice de massa corpórea (IMC) inferior a 30 kg/m2 e hormônio luteinizante (LH) pré-cirúrgico superior 10 UI/L. A técnica operatória de preferência deve ser a realização de 5 a 10 perfurações na superfície de cada ovário bilateralmente por meio do uso de energia monopolar.

Gonadotropin Therapy versus Laparoscopic Ovarian Drilling in Clomiphene Citrate-Resistant Polycystic Ovary Syndrome Patients: A Retrospective Cost-Effectiveness Analysis.

BACKGROUND: Gonadotropin therapy and laparoscopic ovarian drilling (LOD) are treatment options for ovulation induction (OI) in clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS) patients. The current evidence of the cost-effectiveness of both treatments is scarce, conflicting and performed from different health-economic perspectives. METHODS: A retrospective health-economic evaluation was performed from a societal perspective in which human menopausal gonadotropin (hMG) therapy (n = 43) was compared with LOD (n = 35), followed by OI with CC and/or hMG if spontaneous ovulation did not occur within 2 months. Data were collected until the patients were pregnant, with a time limit of 6 months after the onset of treatment. Outcomes were expressed as ongoing pregnancy rate and number of live-born children. RESULTS: The ongoing pregnancy rate was 21/35 (60%) after LOD and 30/43 (69.8%) after hMG treatment (relative risk 0.85, 95% CI 0.61-1.19). The societal cost per patient, up to an ongoing pregnancy, was significantly higher after LOD versus hMG treatment (adjusted mean difference EUR 1,073, 95% CI 180-1,967). CONCLUSION: This economic evaluation based on real-life data shows that the societal cost up to an ongoing pregnancy is less after hMG treatment when compared with LOD surgery in CC-resistant PCOS patients.

Drilling: medical indications and surgical technique.

INTRODUCTION: anovulation is a major cause of female infertility, and polycystic ovary syndrome (PCOS) is the leading cause of anovulation. While undergoing drug-induced ovulation, women with PCOS usually have a satisfactory response recruiting follicles, but some are unable to recruit follicles or often produce an excessive number of follicles, which can result in ovarian hyper-stimulation syndrome and/or multiple pregnancy. Surgical laparoscopy with ovarian "drilling" may prevent or reduce the need for drug-induced ovulation. OBJECTIVE: to identify the current indications of laparoscopic ovarian drilling and the best surgical technique. METHOD: a review of the medical literature based on systematic search in the Medline, Lilacs and Cochrane databases, using as keywords laparoscopy, polycystic ovary syndrome, and drilling. RESULTS: we found 105 articles in the literature, 27 of these highly relevant, describing findings on ovarian drilling. CONCLUSION: laparoscopic drilling is indicated for patients with polycystic ovary syndrome with ovulatory resistance to the use of clomiphene citrate, body mass index less than 30 kg/m2 and preoperative luteinizing hormone above 10 IU/L. The preferred surgical technique should be the realization of 5 to 10 perforations on the surface of each ovary bilaterally using monopolar energy.

Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.

BACKGROUND: Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned both due to the risk of postsurgical adhesions and the introduction of medical ovulation induction. However, women with PCOS who are treated with medical ovulation induction, with drugs such as gonadotrophins, often have an over-production of follicles which may result in ovarian hyperstimulation syndrome and multiple pregnancies. Moreover, gonadotrophins, though effective, are costly and time-consuming and their use requires intensive monitoring. Surgical therapy with laparoscopic ovarian 'drilling' (LOD) may avoid or reduce the need for medical ovulation induction, or may facilitate its usefulness. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions than with traditional surgical approaches. Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception, or that subsequent medical ovulation induction becomes easier. OBJECTIVES: To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS. SEARCH METHODS: We used the search strategy of the Menstrual Disorders and Subfertility Group (MDSG) to search the MDSG Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL and PsycINFO. The keywords included polycystic ovary syndrome, laparoscopic ovarian drilling, electrocautery and diathermy. Searches were conducted in September 2011, and a further search of the MDSG Trials Register was made on 14 May 2012. SELECTION CRITERIA: We included randomised controlled trials of subfertile women with clomiphene-resistant PCOS who undertook laparoscopic ovarian drilling in order to induce ovulation. DATA COLLECTION AND ANALYSIS: This is an update of a previously updated review. There were nine RCTs in the previous version; an additional 16 trials were added in the current (2012) update. All trials were assessed for quality. The primary outcomes were live birth and multiple pregnancy. The secondary outcomes were rate of miscarriage, ovulation and pregnancy rates, ovarian hyperstimulation syndrome (OHSS), quality of life and cost. MAIN RESULTS: Nine trials, including 1210 women, reported on the primary outcome of live birth rate per couple. Live births were reported in 34% of women in the LOD groups and 38% in other medical treatment groups. There were five different comparisons with LOD and there was no evidence of a difference in live births when compared with clomiphene citrate + tamoxifen (OR 0.81; 95% CI 0.42 to 1.53; P = 0.51, 1 trial, n = 150), gonadotrophins (OR 0.97; 95% CI 0.59 to 1.59; P = 0.89, I(2) = 0%, 2 trials, n = 318), aromatase inhibitors (OR 0.84; 95% CI 0.54 to 1.31; P = 0.44, I(2) = 0%, 2 trials, n = 407) or clomiphene citrate (OR 1.21; 95%CI 0.64 to 2.32; 1 trial, n=176, P= 0.05). There was evidence of significantly fewer live births following LOD compared with clomiphene citrate + metformin (OR 0.44; 95% CI 0.24 to 0.82; P = 0.01, I(2) = 78%, 2 trials, n = 159); the high heterogeneity in this subgroup could not be explained by population differences or differences in quality of the trials.Thirteen trials reported on multiple pregnancies (n= 1305 women). There were no cases of multiple pregnancies in either group for clomiphene citrate or aromatase inhibitors compared with LOD. The rate of multiple pregnancies was significantly lower in the LOD group compared with trials using gonadotrophins (OR 0.13; 95% CI 0.03 to 0.52; P=0.004, I(2) = 0%, 5 trials, n = 166). AUTHORS' CONCLUSIONS: There was no evidence of a significant difference in rates of clinical pregnancy, live birth or miscarriage in women with clomiphene-resistant PCOS undergoing LOD compared to other medical treatments. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about the long-term effects of LOD on ovarian function.

Repeat transvaginal ultrasound-guided ovarian interstitial laser treatment improved the anovulatory status in women with polycystic ovarian syndrome.

OBJECTIVE: To assess the effectiveness of repeated transvaginal ultrasound-guided ovarian interstitial laser treatment in the management of anovulatory patients with polycystic ovary syndrome (PCOS). STUDY DESIGN: A retrospective study was performed in our department on 27 anovulatory PCOS women who failed to respond to the first ultrasound-guided transvaginal ovarian interstitial laser treatment. Each woman received a repeat procedure and postoperative rates of ovulation and pregnancy were monitored. RESULTS: Of 27 patients, 18 (66.67%) ovulated spontaneously following the repeated ultrasound-guided transvaginal ovarian interstitial laser treatment Ten women became pregnant within six postoperative months and a cumulative pregnancy rate of 37.04% was achieved. There were no significant operative complications. CONCLUSION: Repeated ultrasound-guided transvaginal ovarian interstitial laser treatment is an effective and safe management in anovulatory PCOS patients who fail to respond or have a transient response to the first transvaginal ovarian interstitial laser treatment.

Ovulation induction in women with polycystic ovary syndrome: an update.

Infertility is frequently caused by anovulation. The affected women present with irregular menstrual cycles and the most common diagnosis is polycystic ovary syndrome. Ovulation induction is commonly used to treat these women. Clomiphene citrate (a selective estrogen receptor modulator or SERM) remains the most used medication for treating this condition. Alternatives that have been used include other SERMs such as tamoxifen, aromatase inhibitors, insulin sensitizing agents, and ovarian drilling. Evidence for and against the effectiveness of these agents has fluctuated over the last decade. Controversies surrounding the use of ovulation induction such as development of functional cysts, high-order multiple births, and development of ovarian cancer have been further studied and some controversies have almost been laid to rest in the last decade.

Long-term outcomes in women with polycystic ovary syndrome initially randomized to receive laparoscopic electrocautery of the ovaries or ovulation induction with gonadotrophins.

BACKGROUND: Long-term effects of laparoscopic electrocautery of the ovaries are unknown. To study the long-term effects of laparoscopic electrocautery of the ovaries and gonadotrophins, we followed women with clomiphene-resistant polycystic ovary syndrome (PCOS) randomly allocated to one of these treatments until 8-12 years after their initial treatment. METHODS: Between February 1998 and October 2001 168 women with clomiphene citrate-resistant PCOS were included in a randomized controlled trial comparing an electrocautery strategy to a strategy starting with rFSH. In 2009 these women were contacted about their reproductive outcome and menstrual cycle regularity. Analysis was by intention-to-treat. We compared time to conception resulting in live birth, subsequent pregnancies, ectopic and multiple pregnancies, menopause, as well as minimal and maximal menstrual cycle length. RESULTS: After 8-12 years, the cumulative proportion of women with a first child was 86% in women who had been allocated to electrocautery versus 81% in women who had been allocated to immediate rFSH [relative ratio (RR): 1.1; 95% confidence interval (CI): 0.92-1.2]. Treatment with electrocautery resulted in a significantly lower need for stimulated cycles to reach a live birth; 53% after electrocautery versus 76% after rFSH (RR: 0.69; 95% CI: 0.55-0.88).The cumulative proportion of women with a second child was 61% after electrocautery versus 46% after immediate rFSH (RR: 1.4; 95% CI: 1.00-1.9). Overall, there were 7 twins out of 134 deliveries (5%) after electrocautery versus 10 twins out of 124 deliveries (8%) in the rFSH group (RR: 0.65; 95% CI: 0.25-1.6). Fifty-four per cent of the women allocated to electrocautery had a regular menstrual cycle 8-12 years after randomization versus 36% in those allocated to rFSH (RR: 1.5; 95% CI: 0.87-2.6). CONCLUSION: In women with clomiphene-resistant PCOS, laparoscopic electrocautery of the ovaries is as effective as ovulation induction with FSH treatment in terms of live births, but reduces the need for ovulation induction or ART in a significantly higher proportion of women and increases the chance for a second child. Clinicians may use these data when informing clomiphene-resistant anovulatory women about treatment options.

Laparoscopic ovarian diathermy vs clomiphene citrate plus metformin as second-line strategy for infertile anovulatory patients with polycystic ovary syndrome: a randomized controlled trial.

OBJECTIVE: The purpose of this study was to compare the effectiveness of laparoscopic ovarian diathermy (LOD) vs clomiphene citrate (CC) plus metformin in infertile patients with CC-resistant polycystic ovary syndrome (PCOS). STUDY DESIGN: Fifty primary infertile patients with CC-resistant PCOS were assigned randomly to receive LOD followed by a 6-month observation (group A) or 6-cycle course of CC plus metformin (group B). Reproductive and safety outcomes were analyzed. RESULTS: No significant difference between 2 groups in pregnancy (15/92 women [16.3%] vs 14/107 women [13.1%]; P = .521) and live-birth (13/92 women [14.1%] vs 12/107 women [11.2%]; P = .536) rates per cycle was observed. With the use of a Cox regression analysis, patients under medical treatment, compared with patients who received surgical treatment, had a relative risk of pregnancy of 1.2 (95% confidence interval, 0.61-2.44; P = .582) and a relative risk of live-birth of 1.4 (95% confidence interval, 0.63-2.96; P = .425). CONCLUSION: LOD and CC plus metformin seem to be 2 effective approaches to treat infertility in patients with CC-resistant PCOS.

Transvaginal ultrasound-guided ovarian interstitial laser treatment in anovulatory women with polycystic ovary syndrome: a randomized clinical trial on the effect of laser dose used on the outcome.

OBJECTIVE: To explore an optimal laser dose of transvaginal ultrasound-guided ovarian interstitial laser coagulation in management of anovulation in patients with polycystic ovary syndrome (PCOS). DESIGN: Randomized, controlled trial. SETTING: A reproductive medical center. PATIENT(S): Eighty women with PCOS and clomiphene citrate-resistant infertility underwent ultrasound-guided transvaginal ovarian interstitial yttrium aluminum garnet laser treatment. All subjects were divided randomly into four groups of A, B, C, and D. INTERVENTION(S): Group A, one coagulation point per ovary; group B, two points; group C, three points; group D, four to five points. MAIN OUTCOME MEASURE(S): Postoperative ovulation rate, pregnancy rate, and some biochemical parameters. RESULT(S): The rates of ovulation in groups C (75.00%, 95% confidence interval [CI]: 51%-91%) and D (80.00%, 95% CI: 56%-94%) within 6 postoperative months were significantly higher than in groups A (5.00%, 95% CI: 0%-25%) and B (15.00%, 95% CI: 3%-38%). The pregnancy rates in groups C (45.00%, 95% CI: 23%-69%) and D (40.00%, 95% CI: 19%-64%) also were significantly higher than in groups A (5.00%, 95% CI: 0-25%) and B (10.00%, 95% CI: 1%-32%). The mean serum T levels were significantly lower in groups C (2.08 +/- 0.62 nmol/L) and D (2.07 +/- 0.42 nmol/L) compared with groups A (3.10 +/- 0.63 nmol/L) and B (2.95 +/- 0.63 nmol/L). CONCLUSION(S): One and two intraovarian laser coagulation points per ovary are associated with poor outcomes. Three points per ovary seem to represent the plateau of effective dose for the ovarian interstitial laser treatment in PCOS.

[Ultrasound-guided transvaginal ovarian interstitial laser treatment in patients with polycystic ovary syndrome: a laser dose-finding study].

OBJECTIVE: To evaluate the clinical and endocrine effectiveness of different laser doses for ultrasound-guided transvaginal ovarian interstitial laser treatment in patients with polycystic ovary syndrome (PCOS). METHODS: Between January 2005 and July 2007, 56 women with clomifene citrate-resistant PCOS selected from the patients who were referred to Shenzhen Maternity and Child Healthcare Hospital with a request for fertility underwent ultrasound-guided transvaginal ovarian interstitial laser treatment. All subjects were randomly divided into four groups of A, B, C and D. In group A, one coagulation point per ovary was done and group B, two points; group C, three points; group D, four to five points. The size of each point was about 10 mm in diameter (the electrical laser was projected persistently for 1-3 min with a power of 3 -5 W). The serum sexual hormone level, ovulation rate and pregnancy rate within six postoperative months were compared among the four groups. RESULTS: (1) The spontaneous ovulation rates of groups A (0) and B (21%) within six postoperative months were significantly lower than groups C (71% ,P <0. 05) and D (79%, P < 0.01). The accumulative pregnancy rates of group C(43%) and D(36%) for six postoperative months were significantly higher than group A (0; P < 0.01, P < 0.05). Although they were also higher than that of group B, no statistical significance was found (P > 0.05). (2) No statistically significant differences were found among four groups when various preoperative hormone values were compared (P > 0. 05). The mean serum luteinizing hormone (LH), testosterone level and LH/ follicle stimulating hormone (FSH) ratio was significantly lower postoperatively in groups C [(6.3 +/- 2.6) U/L, (2.2 +/- 0.7) nmol/L, 1.1 +/- 0.3] and D [(5.8 +/- 2.5) U/L, (2.1 +/- 0.4) nmol/L, 1.0 +/- 0.4] than in groupsA [(11.9 +/- 3.1) U/L, (3.9 +/- 1.6) nmol/L, 2.1 +/- 0.5] and B [(10.4 +/- 3.9) U/L, (3.3 +/- 1.1) nmol/L, 2.0 +/- 0.6], respectively (P < 0.05). The mean LH, testosterone level and LH/FSH ratio reduced more obviously in groups C (42%, 39% and 42%) and D (53%, 40% and 58%) than in groups A (4%, 9% and 16%) and B (11%, 6% and 5%; P < 0.05). All above-mentioned parameters between groups C and D had no statistical significant difference (P > 0.05). CONCLUSIONS: One and two intraovarian laser coagulation points per ovary are associated with poor results. Three points per ovary seem to represent the plateau of effective dose for the ovarian interstitial laser treatment. Increasing the dose above it does not improve the outcome.

The value of measuring anti-Mullerian hormone in women with anovulatory polycystic ovary syndrome undergoing laparoscopic ovarian diathermy.

BACKGROUND: Anti-Müllerian hormone (AMH) has been implicated in the pathogenesis of polycystic ovary syndrome (PCOS). The aim of this study was to measure circulating AMH before laparoscopic ovarian diathermy (LOD) to evaluate its prognostic value for an ovulatory response and to investigate AMH changes after LOD to further explore the effects of LOD. METHODS: This prospective study included anovulatory women with PCOS undergoing LOD (n = 29) or receiving clomiphene citrate (n = 18). Plasma AMH concentrations were measured before and 1 week after treatment. Further measurements of AMH were made at 3- and 6-month follow-up. RESULTS: The pretreatment median (range) plasma AMH concentrations were 6.1 (1.0-21.0) and 5.7 (1.3-9.5) ng/ml in women having LOD and clomiphene citrate treatment, respectively. Women who ovulated after LOD (n = 24) had a significantly (P = 0.032) lower pre-operative AMH [5.6 (1.0-21.0) ng/ml] compared with the non-responders [9.0 (6.1-17.1) ng/ml]. Using receiver-operating characteristic curve analysis, AMH was found to be a useful predictor of no ovulation after LOD with area under the curve of 0.804 (P = 0.025). Using a cut-off of 7.7 ng/ml, AMH had a sensitivity of 78% and a specificity of 76% in the prediction of no ovulation after LOD. For all patients (n = 47, clomiphene citrate or LOD), plasma AMH >or=7.7 ng/ml was associated with a reduced chance of ovulation after treatment (P = 0.004). Following LOD, the median AMH concentration significantly (P = 0.003) decreased to 4.7 (0.3-15.1) ng/ml and remained low at 3- and 6-month follow-up. CONCLUSIONS: Pretreatment circulating AMH level seems to be a good predictor of the ovarian response to LOD.

Evaluation of ovarian adhesion formation after laparoscopic ovarian drilling by second-look minilaparoscopy.

OBJECTIVE: To determine the incidence, site, and grade of ovarian adhesion formation after laparoscopic ovarian drilling (LOD) and analyze the association between the number of punctures made and the incidence and grade of adhesions, and evaluate the lateral distribution of the adhesions. DESIGN: Prospective clinical study. SETTING: University hospital endocrine and infertility center. PATIENT(S): Ninety-six anovulatory infertile women with polycystic ovarian syndrome (PCOS) treated with LOD. INTERVENTION(S): Women were randomized into two study groups of 48 women each, one treated with 6 punctures on the left ovary and 12 on the right, and the other treated with 6 punctures on the right ovary and 12 on the left. A short-term second-look minilaparoscopy was performed to evaluate postsurgical adhesion formation. MAIN OUTCOME MEASURE(S): [1] Evaluation of the incidence and grade (thin, dense, cohesive) of ovarian adhesions; [2] comparative analysis of the incidence and grade of ovarian adhesions between ovaries treated with 6 and 12 punctures; and [3] comparative analysis of the incidence and grade of ovarian adhesions between the two sides. RESULT(S): Adhesion formation was detected in 54 of the 90 women (60%) and in 83 of the 180 ovaries treated (46%). Dense adhesions were more likely to develop on the left ovaries to a statistically significant extent, and independently of the number of ovarian punctures performed (odds ratio [OR] = 4.34, 95% confidence interval [CI] = 1.72-10.94). Logistic regression analysis showed that the incidence of ovarian adhesions was independent of both number of punctures (OR = 1.05, 95% CI = 0.58-1.88) and side (OR = 1.37, 95% CI = 0.76-2.46). CONCLUSION(S): The incidence of ovarian adhesion formation after LOD was high, and their extent and severity was not influenced by the number of ovarian punctures; however, the left ovary appeared more prone to develop severe adhesions than the contralateral one.

Laparoscopic 'drilling' by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.

BACKGROUND: Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned due to the risk of postsurgical adhesions and the introduction of medical ovulation induction with clomiphene and gonadotrophins. However, women with PCOS who are treated with gonadotrophins often have an over-production of follicles which may result in ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. Moreover, gonadotrophins, though effective, are costly and time-consuming requiring intensive monitoring. Surgical therapy with laparoscopic ovarian 'drilling' (LOD) may avoid or reduce the need for gonadotrophins or may facilitate their usefulness. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions than with traditional surgical approaches. Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception or that subsequent medical ovulation induction becomes easier. OBJECTIVES: To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS. SEARCH STRATEGY: We used the search strategy of the Menstrual Disorders and Subfertility Group. SELECTION CRITERIA: We included randomised controlled trials of subfertile women with clomiphene-resistant PCOS who undertook laparoscopic ovarian drilling in order to induce ovulation. DATA COLLECTION AND ANALYSIS: Sixteen trials were identified and nine were included in the review. All trials were assessed for quality criteria. The primary outcomes were live birth, ovulation and pregnancy rates and the secondary outcomes were rates of miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome and cost. MAIN RESULTS: There was no evidence of a difference in live birth or clinical pregnancy rate between LOD and gonadotrophins and the pooled odds ratios (OR) (all studies) were 1.04 (95% CI 0.59 to 1.85) and 1.08 (95% CI 0.69 to 1.71) respectively. Multiple pregnancy rates were lower with ovarian drilling than with gonadotrophins (1% versus 16%; OR 0.13, 95% CI 0.03 to 0.52). There was no evidence of a difference in miscarriage rates between the two groups (OR 0.81, 95% 0.36 to 1.86). AUTHORS' CONCLUSIONS: There was no evidence of a difference in the live birth rate and miscarriage rate in women with clomiphene-resistant PCOS undergoing LOD compared to gonadotrophin treatment. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about long-term effects of LOD on ovarian function.

Ovarian interstitial YAG-laser: an effective new method to manage anovulation in women with polycystic ovary syndrome.

OBJECTIVE: This study was undertaken to assess the effectiveness of transvaginal ultrasound-guided ovarian interstitial laser-coagulation treatment in anovulatory women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Nineteen anovulatory women with clomiphene citrate-resistant PCOS underwent ultrasound-guided transvaginal ovarian interstitial YAG-laser treatment. In this study, serum hormonal level, spontaneous ovulation rate, and pregnancy rate were assessed. RESULTS: With a spontaneous ovulation rate of 84.2%, 16 of 19 cases ovulated regularly during the 6-month postoperative period. The mean serums luteinizing hormone and serum testosterone levels in the second, fourth, and sixth postoperative months were significantly lower than preoperative levels: 5.87 +/- 2.04 IU/L versus 13.17 +/- 3.03 IU/L (P < .001) and 2.98 +/- 1.79 nmol/L versus 5.49 +/- 3.23 nmol/L (P < .001), respectively. The mean luteinizing hormone/follicle-stimulating hormone ratio was also significantly lower postoperatively at 1.09 +/- 0.30 compared with the preoperative 2.85 +/- 1.14 (P < .001). There was a cumulative pregnancy rate at 6 months of 32.3% (6/19) among the subjects. No significant operative complications were encountered. CONCLUSION: The ultrasound-guided transvaginal ovarian interstitial laser treatment may be an effective new method to manage anovulation in PCOS patients.

Transvaginal, ultrasound-guided, ovarian, interstitial laser treatment in anovulatory women with clomifene-citrate-resistant polycystic ovary syndrome.

OBJECTIVE: To assess the effectiveness of transvaginal, ultrasound-guided, ovarian, interstitial laser coagulation treatment in anovulatory women with polycystic ovary syndrome (PCOS). DESIGN: A pilot study. SETTING: Assisted reproductive technology unit. SAMPLE: Twenty-three anovulatory women with clomifene-citrate-resistant PCOS. METHODS: Ultrasound-guided, transvaginal, ovarian, interstitial yttrium-aluminium-garnet laser treatment. MAIN OUTCOME MEASURES: Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, prolactin and estradiol levels, spontaneous ovulation rate and pregnancy rate were measured over 6 months of follow up. RESULTS: Regular ovulation occurred in 19 out of 22 (86.4%) women in the 6 months following ovarian treatment (one woman was lost to follow up). On the postoperative second, fourth and sixth month, the mean serum LH levels were 4.54 SD 1.21 iu/l, 4.90 SD 2.18 iu/l and 4.42 SD 1.03 iu/l, significantly (P < 0.001, P < 0.001, P < 0.001) lower than the preoperative level of 13.89 +/- 3.62 iu/l; the mean serum testosterone levels were 2.69 SD 1.83 nmol/l, 2.42 SD 1.11 nmol/l and 2.28 SD 1.96 nmol/l and significantly (P < 0.001, P < 0.001, P < 0.001) lower than the preoperative baseline value of 5.37 SD 3.09 nmol/l; the mean LH/FSH ratios of 0.93 SD 0.26, 0.88 SD 0.17 and 0.81 SD 0.14 were also significantly lower than the preoperative value of 2.78 SD 1.21 (P < 0.001). Pregnancy occurred in eight women and there was a cumulative pregnancy rate at 6 months of 36% (8/22) among the subjects. There were no significant operative complications. CONCLUSION: Ultrasound-guided, transvaginal, ovarian, interstitial laser treatment appears effective in improving hormonal profiles and inducing ovulation and successful pregnancy in women with clomifene-resistant PCOS.