Evidence summaries and recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome: assessment and treatment of infertility.

STUDY QUESTION: What is the recommended assessment and management of infertile women with polycystic ovary syndrome (PCOS), based on the best available evidence, clinical expertize and consumer preference? SUMMARY ANSWER: International evidence-based guidelines, including 44 recommendations and practice points, addressed prioritized questions to promote consistent, evidence-based care and improve the experience and health outcomes of infertile women with PCOS. WHAT IS KNOWN ALREADY: Previous guidelines on PCOS lacked rigorous evidence-based processes, failed to engage consumer and multidisciplinary perspectives or were outdated. The assessment and management of infertile women with PCOS are inconsistent. The needs of women with PCOS are not being adequately met and evidence practice gaps persist. PARTICIPANTS/MATERIALS SETTING METHODS: Governance included a six continent international advisory and a project board, a multidisciplinary international guideline development group (GDG), consumer and translation committees. Extensive health professional and consumer engagement informed the guideline scope and priorities. The engaged international society-nominated panel included endocrinology, gynaecology, reproductive endocrinology, obstetrics, public health and other experts, alongside consumers, project management, evidence synthesis and translation experts. Thirty-seven societies and organizations covering 71 countries engaged in the process. Extensive online communication and two face-to-face meetings over 15 months addressed 19 prioritized clinical questions involving nine evidence-based reviews and 10 narrative reviews. Evidence-based recommendations (EBRs) were formulated prior to consensus voting within the guideline panel. STUDY DESIGN SIZE DURATION: International evidence-based guideline development engaged professional societies and consumer organizations with multidisciplinary experts and women with PCOS directly involved at all stages. A (AGREE) II-compliant processes were followed, with extensive evidence synthesis. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was applied across evidence quality, desirable and undesirable consequences, feasibility, acceptability, cost, implementation and ultimately recommendation strength. The guideline was peer-reviewed by special interest groups across our partner and collaborating societies and consumer organizations, was independently assessed against AGREE II criteria and underwent methodological review. This guideline was approved by all members of the GDG and has been approved by the NHMRC. MAIN RESULTS AND THE ROLE OF CHANCE: The quality of evidence (QOE) for the EBRs in the assessment and management of infertility in PCOS included very low (n = 1), low (n = 9) and moderate (n = 4) quality with no EBRs based on high-quality evidence. The guideline provides 14 EBRs, 10 clinical consensus recommendations (CCRs) and 20 clinical practice points on the assessment and management of infertility in PCOS. Key changes in this guideline include emphasizing evidence-based fertility therapy, including cheaper and safer fertility management. LIMITATIONS REASONS FOR CAUTION: Overall evidence is generally of low to moderate quality, requiring significantly greater research in this neglected, yet common condition. Regional health systems vary and a process for adaptation of this guideline is provided. WIDER IMPLICATIONS OF THE FINDINGS: The international guideline for the assessment and management of infertility in PCOS provides clinicians with clear advice on best practice based on the best available evidence, expert multidisciplinary input and consumer preferences. Research recommendations have been generated and a comprehensive multifaceted dissemination and translation program supports the guideline with an integrated evaluation program. STUDY FUNDING/COMPETING INTERESTS: The guideline was primarily funded by the Australian National Health and Medical Research Council of Australia (NHMRC) supported by a partnership with ESHRE and the American Society for Reproductive Medicine (ASRM). GDG members did not receive payment. Travel expenses were covered by the sponsoring organizations. Disclosures of conflicts of interest were declared at the outset and updated throughout the guideline process, aligned with NHMRC guideline processes. Dr Costello has declared shares in Virtus Health and past sponsorship from Merck Serono for conference presentations. Prof. Norman has declared a minor shareholder interest in the IVF unit Fertility SA, travel support from Merck and grants from Ferring. Prof. Norman also has scientific advisory board duties for Ferring. The remaining authors have no conflicts of interest to declare.This article was not externally peer-reviewed by Human Reproduction Open.

Power Doppler ultrasound assessment of follicular vascularity in the early follicular phase and its relationship with outcome of in vitro fertilization.

OBJECTIVE: To determine whether ovarian perifollicular blood flow (PFBF) in the early follicular phase (EFP) was associated with treatment outcome. DESIGN: Retrospective longitudinal cohort study. SETTING: Tertiary referral centre/university hospital. PATIENTS: Thirty-four women underwent 37 IVF cycles, which resulted in 35 embryo transfers. INTERVENTIONS: Serial transvaginal scans using power Doppler ultrasound during the follicular phase. Ovarian PFBF of follicles > or =5 mm was subjectively assessed using a modified grading system (grades 0-4). MAIN OUTCOME MEASURES: Ovarian PFBF and pregnancy. RESULTS: Treatment cycles were retrospectively divided into two groups: Group 1 (n=20) had cycles with at least one small (5-10 mm) or medium (11-14 mm) size follicle(s) of high grade (2-4) PFBF on cycle day 5 or 6 or 7; and Group 2 (n=17), had cycles that did not. Group 1 had a significantly higher proportion of high grade large follicles in the late follicular phase (35% vs. 21%) (OR 2.0; 95% CI 1.1-3.7) and higher clinical pregnancy rate (47% vs. 12%) (OR 6.3; CI 1.1-35.7) compared to Group 2. CONCLUSION: High grade ovarian PFBF in the EFP during IVF is associated with both high grade PFBF in the late follicular phase and a higher clinical pregnancy rate.

A prospective, randomised, single-blinded, controlled trial comparing two topical anaesthetic modalities for the application of a tenaculum to the cervix.

The aim of this study was to compare the efficacy of equivalent doses of lignocaine spray vs lignocaine jelly in reducing pain during the application of a tenaculum to the cervix. A total of 58 women undergoing hysterosalpingography were prospectively randomised to receive either two doses of 10% lignocaine spray or 1 ml of 2% lignocaine jelly (both doses equivalent to 20 mg of lignocaine base) topically onto the cervix before tenaculum attachment. There was no difference in pain scores (measured by visual analogue scale and 4-point verbal descriptor scale) between lignocaine spray and lignocaine jelly during the attachment of the tenaculum to the cervix. In conclusion, there was no difference in pain during tenaculum attachment to the cervix following topical application of equivalent doses of either lignocaine jelly or spray.

Longitudinal assessment of ovarian perifollicular and endometrial vascularity by power Doppler ultrasound in pregnant and non-pregnant cycles in the IVF setting.

PURPOSE: This longitudinal study aimed to compare ovarian perifollicular and endometrial blood flow (PFBF and EBF, respectively) during the follicular phase in pregnant and non-pregnant IVF cycles. METHODS: Serial transvaginal scans were performed in 15 subjects undergoing IVF treatment. Both PFBF and EBF were subjectively graded (grades 0-4 for PFBF and grades 1-3 for EBF). After confirmation of clinical pregnancy, the treatment cycles were grouped into 'Pregnant' and 'Non-pregnant' cycles. Ovarian PFBF and EBF were retrospectively compared between the two groups. RESULTS: In pregnant cycles, the proportion of large (> or = 15 mm) follicles with high (24) grade PFBF increased with time throughout the follicular phase, and the proportion of large follicles with poor (0-1) grade PFBF decreased. In non-pregnant cycles these trends were reversed. There was no difference in EBF between the two groups. CONCLUSION: The pattern of ovarian PFBF but not EBF may be predictive of treatment outcome.

Prognostic value of baseline serum oestradiol in controlled ovarian hyperstimulation of women with unexplained infertility.

This study aimed to evaluate the prognostic value of the baseline serum oestradiol E2 level on the cycle pregnancy rate (PR) in women with unexplained infertility (UI) undergoing controlled ovarian hyperstimulation (COH). This study is unique in that it evaluates the effect of cycle day 1 (rather than day 3) E2 levels on cycle PR in a COH setting (without IVF) in women with UI (rather than multiple causes of infertility). Structured as a retrospective cohort study, the setting was the Ovulation Induction Clinic at an academic tertiary care hospital. One hundred and forty-five patients with UI underwent 374 cycles of COH with either human menopausal gonadotrophin (hMG) alone or hMG and clomiphene citrate. Outcome was measured as cycle pregnancy rate (PR) according to the cycle day 1 level of E2. Patients with an E2 level > 150 pmol/l on cycle day 1 of COH achieved a significantly lower PR (4%) compared with those with E2 levels < or = 150 pmol/l (13%). Logistic regression analysis demonstrated that women with day 1 E2 levels below 150 pmol/l were 3.2 times more likely to conceive than those with day 1 E2 levels above 150 pmol/l. Also, the impact of day 1 E2 levels on the chance of pregnancy was independent of day 1 serum FSH levels. Women with UI undergoing COH in our unit with an elevated baseline serum E2 > 150 pmol/l have a significantly lower PR and should be counselled regarding the decreased likelihood of pregnancy.

A spontaneous luteinizing hormone surge is beneficial in women with unexplained infertility undergoing controlled ovarian hyperstimulation without in vitro fertilization.

OBJECTIVE: To determine whether a spontaneous luteinizing hormone (LH) surge influences the pregnancy and miscarriage rate in women with unexplained infertility undergoing controlled ovarian hyperstimulation (COH) without in vitro fertilization. DESIGN: Retrospective cohort study. SETTING: Ovulation Induction Clinic, Royal Hospital for Women, Sydney, Australia. PATIENTS: 145 patients with unexplained infertility who underwent 374 cycles of COH. METHODS: Two types of ovarian stimulation protocols were used: human menopausal gonadotrophin (hMG) alone or hMG and clomiphene citrate (CC). A spontaneous LH surge occurred in 54% of the total cycles. All patients received human chorionic gonadotrophin, whether or not a spontaneous LH surge occurred. All cycles were covered by natural intercourse. MAIN OUTCOME MEASURES: Cycle pregnancy rate and miscarriage rate in cycles with or without a spontaneous LH surge. RESULTS: The cycle pregnancy rate of the LH surge group was significantly higher than that of the no LH surge group for CC/hMG cycles (16.4% and 4.3% respectively, p = 0.02) but not for hMG alone cycles (12.8% and 10% respectively, P > .05). The miscarriage rate was not significantly different between the LH surge group and no LH surge group in either the CC/hMG cycles (30% and 75% respectively, P > .05) or the hMG alone cycles (22% and 38% respectively, P > .05). CONCLUSIONS: In women with unexplained infertility undergoing COH with CC/hMG, the occurrence of a spontaneous LH surge is a favorable event associated with a significantly increased pregnancy rate. The data showed a lower miscarriage rate, but there was insufficient power to confirm or refute this result.