A review of luteinizing hormone and its role in ovarian reserve testing

Background: Ovarian physiology illustrates the synergistic interaction between luteinizing hormone and follicle stimulating hormone in the process of folliculogenesis. While follicle stimulating hormone has been well established as a marker of ovarian reserve, the role of luteinizing hormone has remained somewhat controversial and it seems to have become the ‘forgotten gonadotropin’. The following review aims to investigate the available evidence surrounding luteinizing hormone as an ovarian reserve test and examine the issues which need to be addressed in order to establish it as an ovarian reserve test. It then further attempts to propose a model to direct effective research to ascertain if it does have a role to play in ovarian reserve testing.Findings: The evidence is equivocal in the use of luteinizing hormone as an independent predictor of ovarian reserve. However, there is much stronger evidence to suggest that the follicle stimulating hormone/luteinizing hormone ratio is a useful marker of ovarian reserve- in particular when it is ≥2 and approaching 3. The evidence base for this ratio at present however is sparse. In addition, ovarian reserve tests are fraught with issues over reliability, accuracy, definition and the implications of testing itself. In order to overcome these issues, more quality research needs to be carried out to test this relationship between luteinizing hormone and follicle stimulating hormone

Prevention of Ovarian Hyperstimulation Syndrome: A Review

The following review aims to examine the available evidence to guide best practice in preventing ovarian hyperstimulation syndrome (OHSS). As it stands, there is no single method to completely prevent OHSS. There seems to be a benefit, however, in categorizing women based on their risk of OHSS and individualizing treatments to curtail their chances of developing the syndrome. At present, both Anti-Müllerian Hormone and the antral follicle count seem to be promising in this regard. Both available and upcoming therapies are also reviewed to give a broad perspective to clinicians with regard to management options. At present, we recommend the use of a “step-up” regimen for ovulation induction, adjunct metformin utilization, utilizing a GnRH agonist as an ovulation trigger, and cabergoline usage. A summary of recommendations is also made available for ease of clinical application. In addition, areas for potential research are also identified where relevant

The impact of COVID-19 mitigation measures on fertility patients and clinics around the world

Research question: What is the impact of the response to COVID-19 on the management of fertility treatments and clinical practice around the world? Design: Fertility clinic associates around the world were approached. They completed an online survey containing 33 questions focused on the country's response to the COVID-19 pandemic. Known fertility clinic associates that were contacted comprised scientific directors, medical directors and laboratory managers. Results: There were 43 individual country responses from Asia (13), Africa (3), Europe (17), North America (3), Oceania (2) and South America (5). In nine countries, clinics followed their government body recommendations, in 22 countries there was a combination of recommendations, in 3 countries changes were made by clinic initiative, and 9 countries did not specify. In 34 countries IVF/intracytoplasmic sperm injection (ICSI) and frozen embryo transfer (FET) treatments had an average delay of 56 days (IVF/ICSI) (minimum 0, maximum 160) and 57 days (FET) (minimum 0, maximum 166 days). During the shutdown, the number of freeze-all cycles increased in 22 countries. Only 23 countries reported patients having to undergo a SARS-CoV-2 test, and 20 countries did not report any COVID-19 testing in their clinic. Additional support counselling was offered in 28 countries, partner restrictions at clinics were reported in 41 countries and time between patients’ appointments was increased in 39 countries. Conclusions: The implications of COVID-19 mitigation measures proved the need for government societies to introduce a set protocol that includes requirements such as increased patient counselling and additional guidelines for prioritizing couples who need care most urgently

Melatonin in Assisted Reproductive Technology: A Pilot Double-Blind Randomized Placebo-Controlled Clinical Trial

Purpose: To explore in a small pilot study whether oral melatonin, administered during ovarian stimulation increases clinical pregnancy rate (CPR) after IVF and what dose might be most effective.Methods: Pilot double-blind, dose-finding, placebo-controlled randomized clinical trial in private IVF clinics in Australia between September 2014 and September 2016. One hundred and sixty women having their first cycle of IVF or ICSI were randomized to receive placebo (n = 40), melatonin 2 mg (n = 41), melatonin 4 mg (n = 39), or melatonin 8 mg (n = 40) twice per day (BD) during ovarian stimulation. The primary outcome was CPR. Secondary outcomes included serum and follicular fluid (FF) melatonin concentrations, oocyte/embryo quantity/quality, and live birth rate (LBR). Analysis was performed using the intention-to-treat principle.Results: There was no difference in CPR or LBR between any of the four groups (p = 0.5). When all the doses of melatonin were compared as a group with placebo, the CPR was 21.7% for the former and 15.0% for the latter [OR 1.57 (95% CI 0.59, 4.14), p = 0.4]. There were also no differences between the groups in total oocyte number, number of MII oocytes, number of fertilized oocytes, or the number or quality of embryos between the groups. This is despite mean FF melatonin concentration in the highest dose group (8 mg BD) being nine-fold higher compared with placebo (P < 0.001).Conclusion: No significant differences were observed in CPR or oocyte and embryo parameters despite finding a nine-fold increase in FF melatonin concentration. However, this study was not sufficiently powered to assess differences in CPR and therefore, these results should be interpreted with caution. Because this was a small RCT, a beneficial effect of melatonin on IVF pregnancy rates cannot be excluded and merits confirmation in further, larger clinical trials. ANZCTR (http://www.anzctr.org.au/ Project ID: ACTRN12613001317785)

Concurrent Oral 1 - Therapy of rheumatic disease: OP4. Effectiveness of Rituximab in Rheumatoid Arthritis: Results from the British Society for Rheumatology Biologics Register (BSRBR)

Background: Rituximab (RTX) in combination with methotrexate (MTX) has been licensed since 2006 for the management of severe active rheumatoid arthritis (RA) in patients who have failed at least one anti-tumour necrosis factor (anti-TNF) therapy. Published clinical trials have demonstrated the efficacy of RTX in improving both clinical symptoms and patients' physical function. This study aimed to assess the effectiveness of RTX in RA patients treated in routine clinical practice by examining clinical and patient reported outcomes six months after receiving a first course of RTX. Methods: The analysis involved 550 RA patients registered with the BSRBR, who were starting RTX and were followed up for at least 6 months. Change in Disease Activity Score (DAS28) and European League Against Rheumatism (EULAR) response were used to assess the clinical response while change in Health Assessment Questionnaire (HAQ) score was used to assess the physical function of the patients 6 months after starting RTX. The change in DAS28 and HAQ was compared between seronegative and seropositive patients and anti-TNF naïve patients versus anti-TNF failures. The response was also compared between patients receiving RTX in combination with MTX, other non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) or no nbDMARDs. Results: The mean (s.d.) age of the cohort was 59 (12) years and 78% of the patients were females. The patients had a mean (s.d.) of 15 (10) years of disease duration. 16% were biologic naïve while 84% were anti-TNF failures. 32% of the patients were seronegative and 68% were seropositive. The mean (95% CI) DAS28 at baseline was 6.2 (6.1, 6.3) which decreased to 4.8 (4.7, 4.9) at 6 months of follow up. 16% were EULAR good responders, 43% were moderate responders and 41% were non responders. The mean (95% CI) change in HAQ was −0.1 (−0.2, −0.1) (Table 1). The mean change in DAS28 was similar in seropositive and seronegative patients (p = 0.18) while the anti-TNF naïve patients showed a greater reduction in DAS28 scores than anti-TNF failures (p = 0.05). Patients receiving RTX in combination with MTX showed similar changes in DAS28 and HAQ compared to patients receiving RTX alone or with other nbDMARDs. Conclusions: RTX has proven to be effective in the routine clinical practice. Anti-TNF naïve patients seem to benefit more from RTX treatment than anti-TNF failures. Disclosure statement: The authors have declared no conflicts of interes

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely