Correlation of IVF outcomes and number of oocytes retrieved: a UK retrospective longitudinal observational study of 172 341 non-donor cycles.

OBJECTIVE: How do numbers of oocytes retrieved per In vitro fertilisation (IVF) cycle impact on the live birth rate (LBR) and multiple gestation pregnancy (MGP) rates? DESIGN: Retrospective observational longitudinal study. SETTING: UK IVF clinics. POPULATION: Non-donor IVF patients. MAIN OUTCOME MEASURES: LBR per IVF cycle and MGP levels against number of oocytes retrieved into subgroups: 0, 1-5, 6-15, 16-25, 26-49 oocytes and 50+ oocytes. Relative risk (RR) and 95% CIs were calculated for each group against the intermediate responder with '6-15 oocytes collected'. RESULTS: From 172 341 attempted fresh oocyte retrieval cycles, the oocyte retrieved was: 0 in 10 148 (5.9%) cycles from 9439 patients; 1-5 oocytes in 42 574 cycles (24.7%); 6-15 oocytes in 91 797 cycles (53.3%); 16-25 oocytes in 23 794 cycles (13.8%); 26-49 oocytes in 3970 cycles (2.3%); ≥50 oocytes in 58 cycles (0.033%). The LBRs for the 1-5, 6-15, 16-25 and 26-49 subgroups of oocytes retrieved were 17.2%, 32.4%, 35.3% and 18.7%, respectively. The RR (95% CI) of live birth in comparison to the intermediate group (6-15) for 1-5, 16-25 and 26-49 groups was 0.53 (0.52 to 0.54), 1.09 (1.07 to 1.11) and 0.58 (0.54 to 0.62), respectively. The corresponding MGP rates and RR were 9.2%, 11.0%, 11.4% and 11.3%, respectively and 0.83 (0.77 to 0.90), 1.04 (0.97 to 1.11) and 1.03 (0.84 to 1.26), respectively. CONCLUSION: There was only limited benefit in LBR beyond the 6-15 oocyte group going to the 16-25 oocytes group, after which there was significant decline in LBR. The MGP risk was lower in 1-5 group.

Effect of endometrial scratching on unassisted conception for unexplained infertility: a randomized controlled trial.

OBJECTIVE: To investigate whether endometrial scratching increases the chance of live birth in women with unexplained infertility attempting to conceive without assisted reproductive technology. DESIGN: Randomized, placebo-controlled, participant-blind, multicenter international trial. SETTING: Fertility clinics. PATIENT(S): Women with a diagnosis of unexplained infertility trying to conceive without assistance. INTERVENTION(S): Participants were randomly assigned to receive an endometrial biopsy or a placebo procedure (placement of a biopsy catheter in the posterior fornix, without inserting it into the external cervical os). Both groups performed regular unprotected intercourse with the intention of conceiving over three consecutive study cycles. MAIN OUTCOME MEASURE(S): The primary outcome was live birth. RESULT(S): A total of 220 women underwent randomization. The live birth rate was 9% (10 of 113 women) in the endometrial-scratch group and 7% (7 of 107 women) in the control group (adjusted OR, 1.39; 95% CI, 0.50-4.03). There were no differences between the groups in the secondary outcomes of clinical pregnancy, viable pregnancy, ongoing pregnancy, and miscarriage. Endometrial scratching was associated with a higher pain score on a 10-point scale (adjusted mean difference, 3.07; 95% CI, 2.53-3.60). CONCLUSION(S): This trial did not find evidence that endometrial scratching improves the live birth rate in women with unexplained infertility trying to conceive without assistance. CLINICAL TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry ACTRN12614000656639.

Global inequality in sub-fertility treatment needs safer, cost effective, evidence-based and economically viable choices for patients and stakeholders.

The global increase in subfertility diagnosis and treatments and the rise of private equity investors concentrating on high profits based on in vitro fertilisation (IVF) treatments raise profound societal and economic questions for stakeholders and patients. The question remains as to whose benefits will ultimately be greater when promoting high margins treatment options resulting from cross-border mergers and acquisitions of IVF clinics.This paper covers wide-ranging issues from the erroneously constructed UK National Institute for Health and Care Excellence's (NICE) guidelines on treatment choices, the cost-effectiveness of treatments, the promotion of IVF, and add-ons where evidence remains minimal, the commercial size of the fertility industry. Investment in improving intrauterine insemination (IUI) success rates has understandably been avoided for its short-term impact on the IVF industry. However, IUI efficiency would cut across many of the global subfertility treatment economic and access problems while allowing stakeholder, feepaying, and patients financial savings will likely allow for more funded IVF cycles in acutely deserving cases. The recommendations will help expand choices for globally economically challenged patients' and services while enhancing an ethical and moral dimension towards fertility treatment choices for patients and stakeholders.

A randomized trial of endometrial scratching in women with PCOS undergoing ovulation induction cycles.

RESEARCH QUESTION: Does endometrial scratching improve the chance of a live birth in women with polycystic ovary syndrome (PCOS) undergoing ovulation induction and trying to conceive? DESIGN: An international, multicentre, randomized, sham-controlled trial across six fertility clinics in three countries (New Zealand, UK and Brazil). Women with a diagnosis of PCOS who were planning to commence ovulation induction cycles (at least three cycles) in order to conceive were randomly assigned to receive the pipelle (scratch) procedure or a sham (placebo) procedure in the first cycle of ovulation induction. Women kept a diary of ovulation induction and sexual intercourse timing over three consecutive cycles and pregnancies were followed up to live birth. Primary outcome was live birth and secondary outcomes were clinical pregnancy, ongoing pregnancy, multiple pregnancy, adverse pregnancy outcomes, neonatal outcomes, bleeding following procedure and pain score following procedure. RESULTS: A total of 117 women were randomized; 58 to the scratch group and 59 to the sham group. Live birth occurred in 11 (19%) women in the scratch group and 14 (24%) in the sham group (odds ratio 0.76, 95% confidence interval [CI] 0.30-1.92). Secondary outcomes were similar in each group. Significantly higher pain scores were reported in the scratch group (adjusted mean difference 3.2, 95% CI 2.5-3.9) when measured on a visual analogue scale. CONCLUSION: No difference was detected in live birth rate for women with PCOS who received an endometrial scratch when trying to conceive using ovulation induction; however, uncertainty remains due to the small sample size in this study.

Vesico-vaginal fistula presenting as overactive bladder in a case of Gellhorn pessary for vault prolapse.

An 81-year-old woman with early dementia was on a regular follow-up for change of Gellhorn pessary every 6 months for vault prolapse. She presented with frequency and urgency for 10 months duration 5 years into conservative management. Her symptoms did not improve on anticholinergics and lifestyle modifications. She underwent an opportunistic change of pessary under general anaesthesia coincidental to scalp wound debridement. On removal of the pessary, a gush of urine was noted followed by confirmation of a large vesico-vaginal fistula (VVF). In the initial period of follow-up, she was reviewed by the urogynaecology team and considered to be a poor surgical candidate for a major surgical procedure and was offered conservative measures with incontinence pads and possible indwelling catheter. Serious complications like fistulae can still occur despite well-managed pessary treatment. Earlier presentation with overactive bladder symptoms masked the VVF resulting in delayed diagnosis.

IUI needs fairer appraisal to improve patient and stakeholder choices.

Information supporting IVF at the expense of intrauterine insemination (IUI) has become commonplace, but it lacks critical analyses. Data from poorly practiced IUI, without an equivalent comparison to IVF, has been generalised to recommend a total abandonment of IUI in favour of IVF treatment. Our intention with this paper is to reappraise and balance arguments so that patients and stakeholders can have an unbiased informed choice. We provide information that reveals IUI to predominate over IVF in terms of integrated success, risks and cost to deliver one live birth whilst obviating the maternal and neonatal costs. Exceptional cost savings are demonstrated for IUI over IVF for fee-paying agencies and patients with lowered risks of maternal and neonatal care along with other risks including OHSS, fetal reduction and termination of pregnancies. This analysis supports the view that patients and stakeholders can choose IUI instead of IVF in most instances, except with bilateral tubal blockage and severe male factor infertility. It is apparent that fertility clinics need to re-evaluate and reconsider this field, and IUI can be of benefit to both subfertile patients and the stakeholders.

SARS-CoV-2: diagnostic and design conundrums in the context of male factor infertility.

The question of whether SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus-2 [SARS-CoV-2], leading to the COVID-19 infection) can be harboured in the testes and/or semen is currently unanswered. It is essential to understand the limitations of both antibody and real-time PCR tests in interpreting SARS-CoV-2 data in relation to analyses of semen and testicular tissue without appropriate controls. This article critically analyses the evidence so far on this, and the possible implications. The limitations of diagnostic tests in both sampling and testing methodologies, their validation and their relevance in interpreting data are also highlighted.

Altruism or obligation? The motivations and experience of women who donate oocytes to known recipients in assisted conception treatment: an interpretative phenomenological analysis study.

INTRODUCTION: This qualitative study was conducted to explore the motivations and experience of oocyte donors donating to women known to them. METHODS: Three women who donated oocytes to a close relative were interviewed and data were analysed using an Interpretative Phenomenological Analysis approach. RESULTS: The two key elements noted were "motivations for donation" and "coping with the consequences of oocyte donation". The motivation for donation was influenced by the familial bond that was strengthened by the donation process in some cases. The concept of altruistic oocyte donation stemmed from the narratives of giving the gift of motherhood and gaining a positive self-image and respect from others. Coping with the consequences of oocyte donation tests the donor identity, their wishes for a positive outcome, concerns regarding disclosure of biological motherhood and detachment from the egg and potential child. DISCUSSION: Motivation is influenced by a combination of factors including the rewards of altruistic behaviour, the existence and potential strengthening of the relationship between donor and recipient, but possibly also, a sense of obligation and societal expectations. Oocyte donation can be variously viewed by donors as a unique way of reproductive empowerment or an example of acceding to subtle coercion and thus disempowerment. The study also highlights the clinical as well as ethical importance of providing support services for oocyte donors and recipients.

Effect of metformin taken in the 'fresh' in vitro fertilization/intracytoplasmic sperm injection cycle upon subsequent frozen embryo replacement in women with polycystic ovary syndrome.

OBJECTIVE: We aimed to determine whether metformin when taken during a fresh in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle affects live birth rate (LBR) in subsequent frozen embryo replacement cycles (FERC). DESIGN: A retrospective database analysis of women with polycystic ovary syndrome (PCOS) undergoing FERC at a university teaching hospital between 2002 and 2007 (n = 142). The outcome of FERC in women who had taken metformin in the 'fresh' IVF/ICSI cycle (group A, n = 28) and those who had not (group B, n = 114) were compared. RESULTS: In the first FERC there was a significantly higher LBR (A = 28.6%, B = 12.3%, OR 2.86 95% CI 1.06-7.71). Women who had elective cryopreservation due to ovarian hyperstimulation syndrome risk were found to have significantly higher LBRs if metformin was taken in the fresh IVF/ICSI cycle (A = 44.4%, B = 7.9%, OR 9.33 95% CI 1.60-54.58). CONCLUSIONS: Women with PCOS who take metformin during IVF/ICSI may have a higher LBR in subsequent FERC, especially in those who have elective cryopreservation for OHSS risk. The findings of this study are limited by its retrospective design and small sample size and require confirmation in an adequately powered prospective randomized controlled trial.

A case of pregnancy with Rhesus antibody and bicornuate uterus - a favourable outcome: a case report.

INTRODUCTION: In 1% of Rhesus negative women sensitisation occurs without any overt sensitising event during pregnancy. This accounts for late immunisation during a first pregnancy and is responsible for 18-27% of cases of alloimmunisation. The incidence of congenital uterine anomalies in a fertile population is 3.2% of which 5% are bicornuate uterus. Bicornuate uterus can lead to early miscarriages, preterm labor, fetal growth retardation and congenital malformations. CASE PRESENTATION: A 23-year-old lady in her first pregnancy developed Anti-D antibodies at 28 weeks of gestation without any known sensitising event. In view of increasing anti-D titres, at 36 weeks she was delivered. Incidentally during caesarean section she was found to have bicornuate uterus. The neonate was treated with phototherapy and blood transfusion following delivery. CONCLUSION: Rhesus antibodies when managed by close monitoring and timely delivery can lead to favourable outcome. Bicornuate uterus does not always lead to complications like miscarriage, growth retardation or preterm labour and does not need any special intervention.

The use of a combination of pentoxifylline and tocopherol in women with a thin endometrium undergoing assisted conception therapies--a report of 20 cases.

An optimal thickness of the endometrium is considered to be one of the prerequisites for successful implantation of the embryo. A retrospective analysis was carried out to investigate the use of Pentoxyfylline and tocopherol in improving the endometrial thickness in cases that are unresponsive to conventional therapy. Twenty women with thin endometrium (<6 mm) undergoing either ovulation induction or frozen embryo transfer cycles were prescribed 800 mg of PTX and 1000 IU of Vit E daily. In 11 cases, the etiology for thin endometrium was unknown. The known causes included Turners' syndrome (3), Kallman's syndrome (1), idiopathic hypogonadotrophic hypogonadism (2), premature ovarian failure (1) and Asherman's syndrome (2), none of which had responded to conventional hormonal stimulation. The mean duration of treatment was 8.1 months (+/-4.5, range 1-18 months). The mean thickness of endometrium before and after treatment was 4.37 mm (+/-1.5 mm) and 6.05 mm (+/-1.83 mm), respectively (p = 0.001, 95% CI 0.84-2.5). Overall, 14 (73.7%) women showed improvement in endometrial thickness which was the primary outcome. Pregnancy occurred in eight women (40%) of which three were natural, one had ovulation induction and another five had frozen embryo transfers. We conclude that a combination of pentoxyfylline and tocopherol may improve endometrial growth in resistant cases that are unresponsive to conventional therapy.

Oral misoprostol (100 microg) versus vaginal misoprostol (25 microg) in term labor induction: a randomized comparison.

OBJECTIVE: To compare the efficacy of vaginal misoprostol (25 microg) to oral misoprostol (100 microg) in labor induction at term. METHODS: One hundred and one women at term, with indications for labor induction and cervical Bishop's scores of less than 8, were randomly assigned to receive 100 microg of oral misoprostol or 25 microg vaginal misoprostol after random allocation. This could be repeated every 4 h to a maximum of five doses. The number delivering vaginally within 24 h of the induction was the main outcome measure. RESULTS: Of those who delivered vaginally (74.5% in the oral group vs. 72% in the vaginal group), significantly fewer women delivered within 24 h of induction in the oral group (42.1% vs. 72.2%, RR 0.6, 95% CI 0.4-0.9), with more women receiving more than one dose (45.7% vs. 16.7%, RR 2.7, 95% CI 1.2-6.0). More women in the oral group received oxytocin (68.6% vs. 44%, RR 1.6, 95% CI 1.1-2.2), and the induction to delivery interval was shorter in the vaginal group, although this was not statistically significant [28.9 h (SD 20.2) vs. 20.6 h (SD 16.1), mean difference - 8.3 h, 95% CI - 16.8 to 0.2]. There were no differences in the modes of delivery, uterine hyperstimulation rates or in the neonatal outcomes. CONCLUSION: Vaginal misoprostol in its currently recommended dose of 25 microg seems to be more efficacious than the 100 microg oral dose.