Number of embryos for transfer following in vitro fertilisation or intra-cytoplasmic sperm injection.

BACKGROUND: Transfer of more than one embryo during in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) increases multiple pregnancy rates resulting in an increased risk of maternal and perinatal morbidity. Elective single embryo transfer offers a means of minimising this risk, but this potential gain needs to be balanced against the possibility of jeopardising the overall live birth rate (LBR). OBJECTIVES: To evaluate the effectiveness and safety of different policies for the number of embryos transferred in infertile couples undergoing assisted reproductive technology cycles. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group specialised register of controlled trials, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to March 2020. We handsearched reference lists of articles and relevant conference proceedings. We also communicated with experts in the field regarding any additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing different policies for the number of embryos transferred following IVF or ICSI in infertile women. Studies of fresh or frozen and thawed transfer of one to four embryos at cleavage or blastocyst stage were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial eligibility and risk of bias. The primary outcomes were LBR and multiple pregnancy rate. The secondary outcomes were clinical pregnancy and miscarriage rates. We analysed data using risk ratios (RR), Peto odds ratio (Peto OR) and a fixed effect model. MAIN RESULTS: We included 17 RCTs in the review (2505 women). The main limitation was inadequate reporting of study methods and moderate to high risk of performance bias due to lack of blinding. A majority of the studies had low numbers of participants. None of the trials compared repeated single embryo transfer (SET) with multiple embryo transfer. Reported results of multiple embryo transfer below refer to double embryo transfer. Repeated single embryo transfer versus multiple embryo transfer in a single cycle Repeated SET was compared with double embryo transfer (DET) in four studies of cleavage-stage transfer. In these studies the SET group received either two cycles of fresh SET (one study) or one cycle of fresh SET followed by one frozen SET (three studies). The cumulative live birth rate after repeated SET may be little or no different from the rate after one cycle of DET (RR 0.95, 95% CI (confidence interval) 0.82 to 1.10; I² = 0%; 4 studies, 985 participants; low-quality evidence). This suggests that for a woman with a 42% chance of live birth following a single cycle of DET, the repeated SET would yield pregnancy rates between 34% and 46%. The multiple pregnancy rate associated with repeated SET is probably reduced compared to a single cycle of DET (Peto OR 0.13, 95% CI 0.08 to 0.21; I² = 0%; 4 studies, 985 participants; moderate-quality evidence). This suggests that for a woman with a 13% risk of multiple pregnancy following a single cycle of DET, the risk following repeated SET would be between 0% and 3%. The clinical pregnancy rate (RR 0.99, 95% CI 0.87 to 1.12; I² = 47%; 3 studies, 943 participants; low-quality evidence) after repeated SET may be little or no different from the rate after one cycle of DET. There may be little or no difference in the miscarriage rate between the two groups. Single versus multiple embryo transfer in a single cycle A single cycle of SET was compared with a single cycle of DET in 13 studies, 11 comparing cleavage-stage transfers and three comparing blastocyst-stage transfers.One study reported both cleavage and blastocyst stage transfers. Low-quality evidence suggests that the live birth rate per woman may be reduced in women who have SET in comparison with those who have DET (RR 0.67, 95% CI 0.59 to 0.75; I² = 0%; 12 studies, 1904 participants; low-quality evidence). Thus, for a woman with a 46% chance of live birth following a single cycle of DET, the chance following a single cycle of SET would be between 27% and 35%. The multiple pregnancy rate per woman is probably lower in those who have SET than those who have DET (Peto OR 0.16, 95% CI 0.12 to 0.22; I² = 0%; 13 studies, 1952 participants; moderate-quality evidence). This suggests that for a woman with a 15% risk of multiple pregnancy following a single cycle of DET, the risk following a single cycle of SET would be between 2% and 4%. Low-quality evidence suggests that the clinical pregnancy rate may be lower in women who have SET than in those who have DET (RR 0.70, 95% CI 0.64 to 0.77; I² = 0%; 10 studies, 1860 participants; low-quality evidence). There may be little or no difference in the miscarriage rate between the two groups. AUTHORS' CONCLUSIONS: Although DET achieves higher live birth and clinical pregnancy rates per fresh cycle, the evidence suggests that the difference in effectiveness may be substantially offset when elective SET is followed by a further transfer of a single embryo in fresh or frozen cycle, while simultaneously reducing multiple pregnancies, at least among women with a good prognosis. The quality of evidence was low to moderate primarily due to inadequate reporting of study methods and absence of masking those delivering, as well as receiving the interventions.

Perinatal outcomes after stimulated versus natural cycle IVF: a systematic review and meta-analysis.

Pregnancies resulting from assisted reproductive techniques are at higher risk of adverse perinatal outcomes compared with spontaneous conceptions. Underlying infertility and IVF procedures have been linked to adverse perinatal outcomes. It is important to know if ovarian stimulation influences perinatal outcomes after IVF. A systematic search for relevant studies was conducted up to November 2016 on the following databases: PubMed, EMBASE, DARE and Cochrane Central Register of Controlled Trials. Perinatal outcomes included preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA), large for gestational age (LGA) and congenital anomalies. Data from four studies, which included a total of 96,996 and 704 singleton live births after stimulated IVF and natural or modified natural cycle IVF, were included in the meta-analysis. The risk of PTB (RR 1.27, 95% CI 1.03 to 1.58) and LBW (RR 1.95, 95% CI 1.03 to 3.67) were significantly higher after stimulated compared with natural or modified natural cycle IVF. Data from one study were available for SGA, LGA, congenital anomalies and no significant differences were reported between the groups. This study suggests a higher risk of PTB and LBW after stimulated IVF compared with natural or modified natural IVF, although the absolute increase in risk may be low.

High-risk of preterm birth and low birth weight after oocyte donation IVF: analysis of 133,785 live births.

A higher risk of pregnancy complications occurs after assisted reproductive techniques compared with spontaneously conceived pregnancies. This is attributed to the underlying infertility and assisted reproduction technique procedures involved during treatment. It is a matter of interest whether use of donor oocytes affects perinatal outcomes compared with pregnancies after autologous IVF. Anonymized data were obtained from the Human Fertilization and Embryology Authority. The analysis included 5929 oocyte donation and 127,856 autologous IVF live births. Data from all women who underwent donor oocyte recipient or autologous IVF cycles, both followed with fresh embryo transfer, were analysed to compare perinatal outcomes of preterm birth (PTB) and low birthweight (LBW) after singleton and multiple live births. The risk of adverse perinatal outcomes after oocyte donation was increased: adjusted OR (aOR) 1.56, 99.5% CI 1.34 to 1.80 for PTB and aOR 1.43, 99.5% CI 1.24 to 1.66 for LBW were significantly higher after oocyte donation compared with autologous IVF singletons. The adjusted odds PTB (aOR 1.21, 99.5% CI 1.02 to 1.43) was significantly higher after oocyte donation compared with autologous IVF multiple births. Analysis of this large dataset suggests significantly higher risk of PTB and LBW after ooctye donation compared with autologous IVF pregnancies.

Microsurgical anatomy of the superior sagittal sinus and draining veins.

BACKGROUND: The superior sagittal sinus and the draining cerebral veins are often encountered during the surgery for parasagittal and falx meningiomas and during the interhemisperic transcallosal approaches. A knowledge about the variations from the normally described anatomy helps in anticipating and avoiding problems related to these structures during surgery. AIM: The normal variations in the disposition of the superior sagittal sinus and the number and direction of the draining veins in the Indian population have been studied. SETTINGS AND DESIGN: This is an anatomical study in the fresh cadavers. MATERIALS AND METHODS: Sixty fresh cadavers were examined in the autopsy theatre of the Forensic Medicine Department of the Hospital between March 2011 and February 2013. STATISTICAL ANALYSIS USED: Epi-Info, MS-Excel, and the Statistical Package for the Social Sciences (SPSS) were used for data analysis. RESULTS: The position of the superior sagittal sinus was variable and was up to within 1cm on either side of the sagittal suture. The origin of the superior sagittal sinus varied from the level of foramen caecum to a little posterior from the foramen caecum. The total length of the superior sagittal sagitttal sinus varied from 321 mm to 357 mm (average length 338.77mm); vertical compartments of the sinus were found in three-fourth of the cases studied. Tributaries were found in the herringbone pattern and varied from 13 to 19 on the right and 14 to 19 on the left. The Rolandic vein was the largest draining vein in most of the cases. The superior sagittal sinus drained predominantly to the right transverse sinus in three-fourth of the cases studied. The position of the torcula was variable; often towards the right side and at a higher level. The central sulcus was 49.93 mm posterior to the coronal suture and 130.78 mm anterior to the lambdoid suture. CONCLUSIONS: This is the first study of its kind in Indian population studying the anatomical variations in the anatomy of the superior sagittal sinus that may have a significant bearing on the neurosurgical approaches adopted.

Does SARS Cov-2 infection affect the IVF outcome - A systematic review and meta-analysis.

STUDY QUESTION: What is the effect of SARS Cov-2 on IVF outcome? SUMMARY ANSWER: Mild or asymptomatic Covid-19 infection does not appear to affect clinical or ongoing pregnancy rate after IVF. WHAT IS ALREADY KNOWN: Covid-19 has been shown to affect female and male fertility and reproductive function. Studies have shown variable results regarding impact of Covid-19 on IVF outcome with few reporting impaired ovarian reserve, oocyte and embryo quality, semen parameters, clinical pregnancy rate (CPR) and live birth rate (LBR) while others reported no effect on IVF outcome. STUDY DESIGN, SIZE, DURATION: An electronic database search of PubMed, EMBASE, SCOPUS, WHO Covid-19 database, Clinical trials.gov and Cochrane Central was performed for articles published in English language between 1st January 2020 and 15th October 2022 by two independent reviewers using predefined eligibility criteria We have included observational studies both prospective and retrospective, cohort studies, and case control studies and excluded narrative reviews, case studies, cost-effectiveness studies or diagnostic studies. Risk of bias was assessed using NOS and quality of evidence was graded by GRADE pro. PARTICIPANTS, SETTINGS, METHODS: Studies comparing women undergoing IVF and comparing Covid-19 affected with those unaffected by Covid-19 were included. Also, studies comparing immune group (infected or vaccinated) in the study group and unaffected as controls (historical controls, IVF cycles done prior to Covid-19 outbreak but matched with study group) were included. Those with no comparison group or published in language other than English language or duplicate studies were excluded. MAIN RESULTS AND ROLE OF CHANCE: We identified 5046 records and after full text screening of 82 studies, 12 studies were selected for final review. For the clinical pregnancy rate, there was no difference in the CPR in covid recovered or control patients (OR 0.90, 95 % CI = 0.67 to1.21; I2 = 29 %). Similarly, there was no significant effect on implantation rate (RR 0.92, 95 % CI = 0.68 to1.23; I2 = 31 %) and ongoing pregnancy rate (RR 0.96, 95 % CI = 0.79 to 1.15;I2 = 21 %). The mean number of the oocyte retrieved per patient was not significantly different in both the groups (mean difference 0.52, 95 % CI = -1.45 to 2.49; I2 = 75 %). The certainty of the evidence was low. LIMITATIONS: The meta-analysis is based on observational studies each involving small number of participants. Few studies reported outcomes as per patient while others reported as per cycle, for uniformity we have reported outcomes as per cycle. Sample size in most of studies was small. WIDER IMPLICATIONS OF FINDINGS: This systematic review has not shown any significant effect on the outcome of IVF cycles in patients post Covid-19 recovery compared to controls. But given the sample size, the findings should be considered with caution. REGISTRATION: The review protocol has been registered on PROSPERO (registration number CRD42022314515).

A critique of the Rajasthan Right to Health Bill, 2022 and suggestions for the way forward.

This article discusses a brief history of the concept of Right to Health, the concepts of rights and duties and why both are important and how, in healthcare, one's duty is another's right. The Rajasthan Right to Health Bill, 2022 is analysed and the shortcomings and issues in the Act are discussed. Suggestions to modify the Act and how the same can be implemented are given. In addition, a brief introduction to a successful scheme, the Tamil Nadu Innuyir Kapom Thittam- Nammai Kaakum 48 Scheme, with a similar aim is given. The article concludes that though the Right to Health Act is a noble initiative and is a necessary one; the Act, in its current version, has serious shortcomings and needs to be corrected.

FSH administration at 12-hour intervals for the first 2 days, combined with mandatory GnRH-agonist trigger and blastocyst vitrification in women (<80Kg) with high AMH levels, results in higher cumulative live birth rates and is safer.

We aimed to determine if a programme change to 12 hourly injections of FSH (150 IU per injection) for the first 2 days of stimulation in women with high ovarian reserve (AMH ≥ 30 pmol/L), followed by 24 hourly injections, would elicit increased earlier follicular recruitment, higher egg yields and blastocyst embryos for cryopreservation, leading to potential higher cumulative pregnancy rates, than conventional daily injections throughout. For safety reasons, the approach required mandatory cryopreservation of all blastocysts (mFET group; n = 74), after ovulation trigger with GnRH-agonist, in GnRH-antagonist controlled cycles. The 'Comparator group' (n = 91) comprised women with the same high AMH levels treated with the same base dose of FSH, with the aim of fresh blastocyst transfer and cryopreservation of supernumerary embryos, treated over the preceding 2 years. There was no difference in age, AMH, weight or BMI between the groups. The mFET group achieved higher egg (17.7 versus 11.7; p < 0.001) and embryo (10.9 versus 7.2; p < 0.001) yields and fewer cases with sub-optimal embryo yields (7% versus 22%; p = 0.018). The cumulative live birth rate was superior in the mFET group (73% versus 43%), as was the safety profile, and negligible rate of treatment plan modification.

The Promising Epigenetic Regulators for Refractory Epilepsy: An Adventurous Road Ahead.

The attribution of seizure freedom is yet to be achieved for patients suffering from refractory epilepsy, e.g. Dravet Syndrome (DS). The confined ability of mono-chemical entity-based antiseizure drugs (ASDs) to act directly at genomic level is one of the factors, combined with undetermined seizure triggers lead to recurrent seizure (RS) in DS, abominably affecting the sub-genomic architecture of neural cells. Thus, the RS and ASD appear to be responsible for the spectrum of exorbitant clinical pathology. The RS distresses the 5-HT-serotonin pathway, hypomethylates genes of CNS, and modulates the microRNA (miRNA)/long non-coding RNA (lncRNA), eventually leading to frozen molecular alterations. These changes shall be reverted by compatible epigenetic regulators (EGR) like, miRNA and lncRNA from Breast milk (BML) and Bacopa monnieri (BMI). The absence of studious seizure in SCN1A mutation-positive babies for the first 6 months raises the possibility that the consequences of mutation in SCN1A are subsidized by EGRs from BML. EGR-dependent-modifier gene effect is likely imposed by the other members of the SCN family. Therefore, we advocate that miRNA/lncRNA from BML and bacosides/miRNA from BMI buffer the effect of SCN1A mutation by sustainably maintaining modifier gene effect in the aberrant neurons. The presence of miRNA-155-5p, -30b-5p, and -30c-5p family in BML and miR857, miR168, miR156, and miR158 in BMI target at regulating SCN family and CLCN5 as visualized by Cystoscope. Thus, we envisage that the possible effects of EGR might include (a) upregulating the haploinsufficient SCN1A strand, (b) down-regulating seizure-elevated miRNA, (c) suppressing the seizure-induced methyltransferases, and (d) enhancing the GluN2A subunit of NMDA receptor to improve cognition. The potential of these EGRs from BML and BML is to further experimentally strengthen, long-haul step forward in molecular therapeutics.

Are teenage pregnancies at high risk? A comparison study in a developing country.

OBJECTIVE: The aim of this study was to compare obstetric and perinatal outcome in teenage and non-teenage pregnancies. METHODS: We analyzed retrospective data of 15,498 pregnant patients who delivered from March 2008 to April 2009 in Jawaharlal Institute of Postgraduate Medical Education and Research, a referral tertiary care and teaching hospital in Pondicherry, South India. Girls aged ≤ 19 years were compared with pregnancy outcomes in women aged > 19 years who delivered in the same hospital during the study period. A total of 620 teenage pregnancies were compared with 14,878 non-teenage women. The obstetric and perinatal outcome was compared in the study and control groups using t test with Yates correction. We calculated Odds ratio (OR), 95% confidence intervals(CI) and p values; p < 0.005 was considered significant. RESULTS: The incidence of teenage pregnancy in the study was 4%. A signicant proportion of teenage mothers were in their first pregnancies and their mean age was 18.04 years. Our study showed a significantly higher incidence of anaemia, past dates, premature rupture of membranes (PROM), normal vaginal delivery, episiotomy, low birth weight, and a significantly lower incidence of caesarean sections/perineal tears in teenage mothers compared to other mothers. In contrast, the incidence of hypertension, intrauterine growth restriction of fetus, pre-term labour and postpartum haemorrhage were similar in both the groups. CONCLUSION: The data in our study should throw more light on the current thinking of the obstetrical problems facing teenage mothers, in which some of our results support and others refute several long held beliefs about the risks in teenage pregnancy. Early booking, adequate antenatal care and delivery by trained people should improve the obstetric and perinatal outcome in teenage pregnancies, which is still an unresolved problem inspite of various government programmes in developing countries.

Ethnic and demographic variation in consenting for research in the context of fertility treatment.

A retrospective service evaluation was conducted in a tertiary fertility clinic to assess factors influencing the inclinations of individuals to consent for their information to be used for research (non-contact research) and their willingness to be contacted for future research studies (contact research). Self-reported data on ethnicity and country of birth were obtained from the HFEA registration forms of 18,384 patients undergoing fertility treatment. Socio-economic deprivation was assessed using the Index of Multiple Deprivation (IMD) determined by postcode. Analysis of data indicated that 24% were of non-white ethnicity, 32% had been born overseas and 46% resided in more deprived areas. Non-white patients were significantly less likely to consent to research than white patients (contact research: aOR 0.36, 95% CI 0.33 to 0.39; non-contact research: aOR 0.35, 95% CI 0.32 to 0.38), as were patients born overseas (contact research: aOR 0.86, 95% CI 0.79 to 0.94; non-contact research: aOR 0.89, 95% CI 0.82 to 0.97), and those living in more deprived areas (contact research: aOR 0.85, 95% CI 0.80 to 0.91; non-contact research: aOR 0.79, 95% CI 0.74 to 0.85). The findings indicate that ethnicity, country of birth and socio-economic factors are independently associated with willingness to participate in research.

Ethnic variation in the live birth rate and perinatal outcomes following frozen embryo transfer: an analysis of the HFEA database from 2000 to 2016.

The literature suggests that ethnicity affects live birth rate (LBR) and preterm birth (PTB) rate after fresh but not frozen embryo transfer (FET). We analysed 64,530 FET cycles from 2000 to 2016 using the Human Fertilisation and Embryology Authority (HFEA) database. Ethnicity was recorded for 43,735 as White British, 3,034 as Indian, 1,946 as Pakistani, 1,400 as Black African, 1,090 as White Irish, 520 as Chinese, 319 as Bangladeshi and 277 as Black Caribbean women. The LBR per FET when compared with White British women (26.1%) was significantly reduced in women of White Irish (23.4%; adjusted Odds Ratio (aOR) 0.85, 95% CI 0.73 to 1.00), Indian (25.2%; aOR 0.95, 95% CI 0.91 to 0.99), Bangladeshi (21.1%; aOR 0.87, 95% CI 0.79 to 0.95) and Pakistani (25.7%; aOR 0.97, 95% CI 0.94 to 0.99) ethnicities. The PTB rate, when compared with White British women (8.4%) was significantly higher for women of Indian (11.1%; aOR 1.38, 95% CI 1.06 to 1.79), Pakistani (11.8%; aOR 1.49, 95% CI 1.09 to 2.03) and White Irish (12.3%; aOR 1.55, 95% CI 1.01 to 2.38) ethnicities. This study suggests that FET outcomes are influenced by ethnicity.

Single nucleotide polymorphism array versus karyotype for prenatal diagnosis in fetuses with abnormal ultrasound: A systematic review and meta-analysis.

OBJECTIVE: To estimate the incremental yield of single nucleotide polymorphism (SNP) array over karyotype and to assess the diagnostic accuracy of SNP array as a stand-alone test versus SNP array with karyotype in detecting chromosomal abnormalities for prenatal diagnosis in women with an abnormal fetal ultrasound. STUDY DESIGN: Studies in which SNP array and karyotype had been used for diagnosing chromosomal aberrations in fetuses with abnormal ultrasound findings were included. A systematic search of relevant studies published in the English language in EMBASE, PubMed, CENTRAL, CDSR (Cochrane database of systematic reviews), SCOPUS and Web of science between 1996 and May 2020 was performed. Primary outcome was incremental yield of SNP array over karyotype (number of patients with abnormalities detected by SNP array over number of patients with normal karyotype). Other outcomes included diagnostic accuracy of SNP array alone versus SNP array and karyotype for prenatal diagnosis. Pooled sensitivities, specificities, and their 95% confidence intervals (CI) were presented. RESULT(S): Seven studies were included. The incremental yield of SNP array over karyotype was 8% (95% Confidence interval, CI 4-12%) while incremental yield of karyotype over SNP array in foetus with abnormal ultrasound was 0% (95% CI 0-1%). The agreement between SNP array and karyotype was 92%. The variant of unknown significance rates ranged between 4 and 8 %. The pooled sensitivity and specificity of SNP array versus SNP array and karyotype was 0.97 (95% CI 0.92-0.99) and 1.00 (95% CI1.00-1.00), respectively. CONCLUSION(S): SNP array provides additional information on chromosomal abnormalities over and above conventional karyotype. When used as a stand-alone test, SNP array performs favourably as a diagnostic modality when compared against SNP array and karyotype for prenatal diagnosis with an abnormal fetal ultrasound.

Management of recurrent implantation failure: British Fertility Society policy and practice guideline.

Recurrent implantation failure (RIF) is defined as the absence of a positive pregnancy test after three consecutive transfers of good quality embryos. There remains significant variation in clinical practice in the management of RIF. This British Fertility Society (BFS) Policy and Practice guideline analyses the evidence for investigations and therapies that are employed in RIF and provides recommendations for clinical practice and for further research. Evidence for investigations of sperm and egg quality, uterine and adnexal factors, immunological factors and thrombophilia, endocrine conditions and genetic factors and for associated therapies have been evaluated. This guideline has been devised to assist reproductive medicine specialists and patients in making shared decisions concerning management of RIF. Finally, suggestions for research towards improving understanding and management of RIF have also been provided.

Is a woman's chronological age or 'ovarian age' more important in determining perinatal outcome after assisted reproductive treatment?

Ovarian reserve (OR) decreases as women get older but there is considerable variation in the rate at which this occurs. Older women are at increased risk of complications during pregnancy. The aim of the study was to determine whether poor OR influences perinatal outcomes independent of age. All fresh IVF/ICSI cycles in which a single embryo was transferred between 1 January 2010 and 31 December 2016 were reviewed. An anti-Müllerian hormone (AMH) concentration of ≤5.4 pmol/l was considered poor and 5.41-24.99 pmol/l normal. Data were collected regarding cycle outcome, congenital anomalies, gestational age at delivery and birth weight. A total of 1520 women were included, of whom 1197 had normal OR and the remaining 323 had poor OR. Once pregnant, after adjusting for maternal age, women with poor OR (n = 109) were no more likely to experience a biochemical pregnancy or miscarriage (41.3% versus 41.6%, p = 0.809) than women with normal OR (n = 596). There were no significant differences in rates of congenital anomalies (1.8% versus 1.2%, p = 0.636), birth weight (3272 ± 630.7 g versus 3376.4 ± 576.3 g, p = 0.216) or gestational age at delivery (38.9 ± 2.3 weeks versus 39.1 ± 2.1 weeks, p = 0.517) between women with normal or poor OR. OR does not appear to affect pregnancy loss rates, incidence of congenital anomalies, birth weight, or gestational age at delivery after adjusting for maternal age.

Can the ethnic differences in IVF cycle outcome be influenced by the impact of BMI?

The objective of this study was to investigate the role of Body Mass Index (BMI) in influencing ethnic variation in IVF outcomes. This retrospective cohort study included women (having BMI between 19 to 30 kg/m2) undergoing their first IVF cycle with fresh blastocyst transfer at a single IVF unit between 2010 and 2015. In summary, South Asian women had a lower live birth rate (LBR) (27% vs 44.7%, aOR 0.41, 95% CI 0.29 to 0.59) than Caucasian women. Subgroup analysis revealed a significantly lower LBR for South Asian women when their BMI was 25-25.9 kg/m2 (21.4% vs 47.4%, aOR 0.19, 95% CI 0.04 to 0.84), 26-26.9 kg/m2 (30.0% vs 55.0%, aOR 0.26, 95% CI 0.08 to 0.86) and 27-27.9 kg/m2 (14.3% vs 39.4%, aOR 0.14, 95% CI 0.03 to 0.70) with no significant differences in the other BMI subgroups. These results suggest that a lower BMI cut-off may be indicated for South Asian women having IVF when compared to Caucasian women. These findings are novel but are limited because they are from a single centre. However, the results should prompt further research into the subject by multi-centre studies with larger number of IVF cycles analysed.

Concordance between systematic reviews of randomized controlled trials in assisted reproduction: an overview.

STUDY QUESTION: Are systematic reviews published within a 3-year period on interventions in ART concordant in their conclusions? SUMMARY ANSWER: The majority of the systematic reviews published within a 3-year period in the field of assisted reproduction on the same topic had discordant conclusions. WHAT IS KNOWN ALREADY: Systematic reviews and meta-analyses have now replaced individual randomized controlled trials (RCTs) at the top of the evidence pyramid. There has been a proliferation of systematic reviews and meta-analyses, many of which suffer from methodological issues and provide varying conclusions. STUDY DESIGN SIZE DURATION: We assessed nine interventions in women undergoing ART with at least three systematic reviews each, published from January 2015 to December 2017. PARTICIPANTS/MATERIALS SETTING METHODS: The systematic reviews which included RCTs were considered eligible for inclusion. The primary outcome was extent of concordance between systematic reviews on the same topic. Secondary outcomes included assessment of quality of systematic reviews, differences in included studies in meta-analyses covering the same search period, selective reporting and reporting the quality of evidence. MAIN RESULTS AND THE ROLE OF CHANCE: Concordant results and conclusions were found in only one topic, with reviews in the remaining eight topics displaying partial discordance. The AMSTAR grading for the majority of the non-Cochrane reviews was critically low whilst it was categorized as high for all of the Cochrane reviews. For three of the nine topics, none of the included systematic reviews assessed the quality of evidence. We were unable to assess selective reporting as most of the reviews did not have a pre-specified published protocol. LIMITATIONS REASONS FOR CAUTION: We were limited by the high proportion of reviews lacking a pre-specified protocol, which made it impossible to assess for selective reporting. Furthermore, many reviews did not specify primary and secondary outcomes which made it difficult to assess reporting bias. All the authors of this review were Cochrane review authors which may introduce some assessment bias. The categorization of the review's conclusions as beneficial, harmful or neutral was subjective, depending on the tone and wording of the conclusion section of the review. WIDER IMPLICATIONS OF THE FINDINGS: The majority of the systematic reviews published within a 3-year period on the same topic in the field of assisted reproduction revealed discordant conclusions and suffered from serious methodological issues, hindering the process of informed healthcare decision-making. STUDY FUNDING/COMPETING INTERESTS: All the authors are Cochrane authors. M.S.K. is an editorial board member of Cochrane Gynaecology and Fertility group. No grant from funding agencies in the public, commercial or not-for-profit sectors was obtained.

Antioxidant pretreatment for male partner before ART for male factor subfertility: a randomized controlled trial.

STUDY QUESTION: Does oral antioxidant pretreatment for the male partner improve clinical pregnancy rate in couples undergoing ART for male factor subfertility? SUMMARY ANSWER: There was no significant difference in clinical pregnancy rate following oral antioxidant pretreatment for male partner in couples undergoing ART for male factor subfertility compared to no pretreatment. WHAT IS KNOWN ALREADY: Damage to sperm mediated by reactive oxygen species (ROS) contributes significantly to male factor infertility. The ROS-related injury reduces fertilization potential and adversely affects the sperm DNA integrity. Antioxidants act as free radical scavengers to protect spermatozoa against ROS induced damage. During ART, use of sperms which have been exposed to ROS-mediated damage may affect the treatment outcome. Pretreatment with antioxidants may reduce the ROS-mediated sperm DNA damage. Currently, antioxidants are commonly prescribed to men who require ART for male factor subfertility but there is ambiguity regarding their role. STUDY DESIGN SIZE DURATION: This was an open label, randomized controlled trial conducted at a tertiary level infertility clinic between February 2013 and October 2019. The trial included 200 subfertile couples who were undergoing ART treatment for male factor subfertility. PARTICIPANTS/MATERIALS SETTING METHODS: Couples were randomized into treatment arm (n = 100) and control arm (n = 100). In the treatment arm, the male partner received oral antioxidants (Vitamin C, Vitamin E and Zinc) for 3 months just prior to the ART cycle. In the control arm, no antioxidant was given to the male partner. The primary outcome was clinical pregnancy rate, while live birth rate (LBR), miscarriage rate and changes in semen parameters were the secondary outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: Out of 200 women randomized, 135 underwent embryo transfer as per protocol. Following intention to treat analysis, no significant difference was noted in clinical pregnancy (36/100, 36% vs 26/100, 26%; odds ratio (OR) 1.60, 95% CI 0.87 to 2.93) and LBR (25/100, 25% vs 22/100, 22%; OR 1.18, 95% CI 0.61 to 2.27) between antioxidant and no pretreatment arms. The clinical pregnancy rate per embryo transfer was significantly higher following antioxidant pretreatment (35/64, 54.7% vs 26/71, 36.6%; OR 2.09, 95% CI 1.05 to 4.16) compared to no pretreatment. There was no significant difference in LBR per embryo transfer (25/64, 39.1%, vs 22/71, 31.0%; OR 1.43, 95% CI 0.70 to 2.91) after antioxidant pretreatment versus no pretreatment. The semen parameters of sperm concentration (median, interquartile range, IQR) (18.2, 8.6 to 37.5 vs 20.5, 8.0 to 52.5, million/ml; P = 0.97), motility (median, IQR) (34, 20 to 45 vs 31, 18 to 45%; P = 0.38) and morphology (mean ± SD) (2.0 ± 1.4 vs 2.2 ± 1.5%; P = 0.69) did not show any significant improvement after intake of antioxidant compared to no treatment, respectively. LIMITATIONS REASONS FOR CAUTION: The objective assessment of sperm DNA damage was not carried out before and after the antioxidant pretreatment. Since the clinicians were aware of the group allotment, performance bias cannot be ruled out. WIDER IMPLICATIONS OF THE FINDINGS: The current study did not show any significant difference in clinical pregnancy and LBR following antioxidant pretreatment for the male partner in couples undergoing ART for male subfertility. The findings need further validation in a larger placebo-controlled randomized trial. STUDY FUNDING/COMPETING INTERESTS: This trial has been funded by Fluid Research grant of Christian Medical College, Vellore (internal funding). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: CTRI/2013/02/003431. TRIAL REGISTRATION DATE: 26 February 2013. DATE OF FIRST PATIENT'S ENROLMENT: 11 February 2013.

Clinical adjuncts in in vitro fertilization: a growing list.

A growing list of clinical adjuncts are being used during in vitro fertilization (IVF) treatment. Most of these IVF add-ons (such as growth hormone, aspirin, heparin, dehydroepiandrostenedione, testosterone, male and female antioxidants, and screening hysteroscopy) are being introduced into routine clinical practice in a hurried manner without any clear evidence of benefit in most cases. These add-ons make the IVF more complicated and increase the overall cost for the treatment, which is borne by the couples and health care providers. Our current review found no high-quality evidence to support the use of these IVF add-ons in routine practice. Large, well-designed, randomized trials must be conducted to evaluate the effectiveness and safety of these interventions. There is also a pressing need to develop an evidence-dictated mechanism for introducing newer interventions into routine clinical settings.

Iron overload directly affecting the ovaries in a patient with Diamond-Blackfan anaemia: a case report.

Iron is a 'one-way' element and the primary point of regulation of body iron stores is at the level of intestinal iron absorption. Repeated blood transfusions for congenital anaemias bypass this regulatory checkpoint and inevitably lead to iron overload in the long-term. Iron overload causes multi-organ dysfunction of the heart, liver, pancreas and joints. It also causes reproductive toxicity primarily through its damaging effect on the anterior pituitary leading to hypogonadotrophic hypogonadism. Another less understood mechanism of reproductive toxicity is direct gonadal damage of excess free iron. In this article, we present the case of a 24-year-old woman with Diamond-Blackfan anaemia who presented to our unit seeking fertility assistance. The evaluation revealed a combination of hypogonadotrophic hypogonadism and reduced ovarian reserve along with evidence of severe iron overload. A literature search along with input from clinical experts has allowed us to counsel the patient to help her make an informed choice. A multi-disciplinary approach which would include initial optimization of pre-conceptional health with aggressive iron chelation therapy and subsequent ovulation induction with gonadotrophins has been planned, failing which, egg donation may be the only viable alternative.

Use of embryo culture supernatant to improve clinical outcomes in assisted reproductive technology: a systematic review and meta-analysis.

We planned a systematic review and meta-analysis of randomized clinical trials (RCTs) to examine the best available evidence regarding the intrauterine instillation of embryo culture supernatant prior to embryo transfer in ART. The outcomes were: (i) live birth; (ii) clinical pregnancy; (iii) multiple pregnancy; and (iv) miscarriage rates. Five RCTs were considered eligible and available for qualitative synthesis. Due to clinical heterogeneity, results from only two trials were combined for the meta-analysis. The live birth rate (risk ratio [RR], 0.47; 95% confidence interval [CI] 0.22-0.98; one study, 60 participants, low-quality evidence) was found to be significantly lower with intrauterine instillation of embryo culture supernatant compared to no intervention. The clinical pregnancy rate was similar between the embryo culture supernatant group and the control group (RR 1.02 RR, 95% CI 0.77-1.36; two trials, 156 participants, I2 = 0%). To conclude, this review did not find any improvement in clinical pregnancy rate with the intrauterine instillation of embryo culture supernatant prior to embryo transfer compared to no intervention in women undergoing ART and we remain uncertain regarding its effect on live birth rate.