Growth hormone for in vitro fertilisation (IVF).

BACKGROUND: In an effort to improve outcomes of in vitro fertilisation (IVF) cycles, the use of growth hormone (GH) has been considered as adjuvant treatment in ovarian stimulation. Improving the outcomes of IVF is especially important for women with infertility who are considered 'poor responders'. We have compared the outcomes of IVF with adjuvant GH versus no adjuvant treatment in routine use, and specifically in poor responders. OBJECTIVES: To assess the effectiveness and safety of growth hormone as an adjunct to IVF compared to standard IVF for women with infertility SEARCH METHODS: We searched the following databases (to November 2020): Cochrane Gynaecology and Fertility (CGF) Group specialised register, CENTRAL, MEDLINE, Embase, CINAHL, Epistemonikos database and trial registers together with reference checking and contact with study authors and experts in the field to identify additional trials. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) of adjuvant GH treatment in IVF compared with no adjuvant treatment for women with infertility. We excluded trials where additional adjuvant treatments were used with GH. We also excluded trials comparing different IVF protocols. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures recommended by Cochrane. Two review authors independently performed assessment of trial risk of bias and extraction of relevant data. The primary review outcome was live birth rate. The secondary outcomes were clinical pregnancy rate, oocytes retrieved, embryo transfer, units of gonadotropin used and adverse events, i.e. ectopic pregnancy, multiple pregnancy, ovarian hyperstimulation syndrome (OHSS), congenital anomalies, oedema. MAIN RESULTS: We included 16 RCTs (1352 women). Two RCTs (80 women) studied GH in routine use, and 14 RCTs (1272 women) studied GH in poor responders. The evidence was low to very low certainty, the main limitations being risk of bias, imprecision and heterogeneity. Adjuvant growth hormone compared to no adjuvant: routine use for in vitro fertilisation (IVF) The evidence is very uncertain about the effect of GH on live birth rate per woman randomised for routine use in IVF (odds ratio (OR) 1.32, 95% confidence interval (CI) 0.40 to 4.43; I2 = 0%; 2 trials, 80 participants; very low-certainty evidence). If the chance of live birth without adjuvant GH is assumed to be 15%, the chance of live birth with GH would be between 6% and 43%. There was insufficient evidence to reach a conclusion regarding clinical pregnancy rates per woman randomised, number of women with at least one oocyte retrieved per woman randomised and embryo transfer achieved per woman randomised; reported data were unsuitable for analysis. The evidence is very uncertain about the effect of GH on mean number of oocytes retrieved in normal responders (mean difference (MD) -0.02, 95% CI -0.79 to 0.74; I2 = 0%; 2 trials, 80 participants; very low-certainty evidence). The evidence is very uncertain about the effect of GH on mean units of gonadotropin used in normal responders (MD 13.57, 95% CI -112.88 to 140.01; I2 = 0%; 2 trials, 80 participants; very low-certainty evidence). We are uncertain of the effect of GH on adverse events in normal responders. Adjuvant growth hormone compared to no adjuvant: use in poor responders for in vitro fertilisation (IVF) The evidence is very uncertain about the effect of GH on live birth rate per woman randomised for poor responders (OR 1.77, 95% CI 1.17 to 2.70; I2 = 0%; 8 trials, 737 participants; very low-certainty evidence). If the chance of live birth without adjuvant GH is assumed to be 11%, the chance of live birth with GH would be between 13% and 25%. Adjuvant GH results in a slight increase in pregnancy rates in poor responders (OR 1.85, 95% CI 1.35 to 2.53; I2 = 15%; 11 trials, 1033 participants; low-certainty evidence). The results suggest, if the pregnancy rate without adjuvant GH is assumed to be 15%, with GH the pregnancy rate in poor responders would be between 19% and 31%. The evidence suggests that GH results in little to no difference in number of women with at least one oocyte retrieved (OR 5.67, 95% CI 1.54 to 20.83; I2 = 0%; 2 trials, 148 participants; low-certainty evidence). If the chance of retrieving at least one oocyte in poor responders was 81%, with GH the chance is between 87% and 99%. There is a slight increase in mean number of oocytes retrieved with the use of GH for poor responders (MD 1.40, 95% CI 1.16 to 1.64; I2 = 87%; 12 trials, 1153 participants; low-certainty evidence). The evidence is very uncertain about the effect of GH on embryo transfer achieved (OR 2.32, 95% CI 1.08 to 4.96; I2 = 25%; 4 trials, 214 participants; very low-certainty evidence). If the chance of achieving embryo transfer is assumed to be 77%, the chance with GH will be 78% to 94%. Use of GH results in reduction of mean units of gonadotropins used for stimulation in poor responders (MD -1088.19, 95% CI -1203.20 to -973.18; I2 = 91%; 8 trials, 685 participants; low-certainty evidence). High heterogeneity in the analyses for mean number of oocytes retrieved and units of GH used suggests quite different effects according to differences including in trial protocols (populations, GH dose and schedule), so these results should be interpreted with caution. We are uncertain of the effect of GH on adverse events in poor responders as six of the 14 included trials failed to report this outcome. AUTHORS' CONCLUSIONS: The use of adjuvant GH in IVF treatment protocols has uncertain effect on live birth rates and mean number of oocytes retrieved in normal responders. However, it slightly increases the number of oocytes retrieved and pregnancy rates in poor responders, while there is an uncertain effect on live birth rates in this group. The results however, need to be interpreted with caution, as the included trials were small and few in number, with significant bias and imprecision. Also, the dose and regimen of GH used in trials was variable. Therefore, further research is necessary to fully define the role of GH as adjuvant therapy in IVF.

Position in the second stage of labour for women without epidural anaesthesia.

BACKGROUND: For centuries, there has been controversy around whether being upright (sitting, birthing stools, chairs, squatting, kneeling) or lying down (lateral (Sim's) position, semi-recumbent, lithotomy position, Trendelenburg's position) have advantages for women giving birth to their babies. This is an update of a review previously published in 2012, 2004 and 1999. OBJECTIVES: To determine the possible benefits and risks of the use of different birth positions during the second stage of labour without epidural anaesthesia, on maternal, fetal, neonatal and caregiver outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (30 November 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised, quasi-randomised or cluster-randomised controlled trials of any upright position assumed by pregnant women during the second stage of labour compared with supine or lithotomy positions. Secondary comparisons include comparison of different upright positions and the supine position. Trials in abstract form were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and assessed trial quality. At least two review authors extracted the data. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: Results should be interpreted with caution because risk of bias of the included trials was variable. We included eleven new trials for this update; there are now 32 included studies, and one trial is ongoing. Thirty trials involving 9015 women contributed to the analysis. Comparisons include any upright position, birth or squat stool, birth cushion, and birth chair versus supine positions.In all women studied (primigravid and multigravid), when compared with supine positions, the upright position was associated with a reduction in duration of second stage in the upright group (MD -6.16 minutes, 95% CI -9.74 to -2.59 minutes; 19 trials; 5811 women; P = 0.0007; random-effects; I² = 91%; very low-quality evidence); however, this result should be interpreted with caution due to large differences in size and direction of effect in individual studies. Upright positions were also associated with no clear difference in the rates of caesarean section (RR 1.22, 95% CI 0.81 to 1.81; 16 trials; 5439 women; low-quality evidence), a reduction in assisted deliveries (RR 0.75, 95% CI 0.66 to 0.86; 21 trials; 6481 women; moderate-quality evidence), a reduction in episiotomies (average RR 0.75, 95% CI 0.61 to 0.92; 17 trials; 6148 women; random-effects; I² = 88%), a possible increase in second degree perineal tears (RR 1.20, 95% CI 1.00 to 1.44; 18 trials; 6715 women; I² = 43%; low-quality evidence), no clear difference in the number of third or fourth degree perineal tears (RR 0.72, 95% CI 0.32 to 1.65; 6 trials; 1840 women; very low-quality evidence), increased estimated blood loss greater than 500 mL (RR 1.48, 95% CI 1.10 to 1.98; 15 trials; 5615 women; I² = 33%; moderate-quality evidence), fewer abnormal fetal heart rate patterns (RR 0.46, 95% CI 0.22 to 0.93; 2 trials; 617 women), no clear difference in the number of babies admitted to neonatal intensive care (RR 0.79, 95% CI 0.51 to 1.21; 4 trials; 2565 infants; low-quality evidence). On sensitivity analysis excluding trials with high risk of bias, these findings were unchanged except that there was no longer a clear difference in duration of second stage of labour (MD -4.34, 95% CI -9.00 to 0.32; 21 trials; 2499 women; I² = 85%).The main reasons for downgrading of GRADE assessment was that several studies had design limitations (inadequate randomisation and allocation concealment) with high heterogeneity and wide CIs. AUTHORS' CONCLUSIONS: The findings of this review suggest several possible benefits for upright posture in women without epidural anaesthesia, such as a very small reduction in the duration of second stage of labour (mainly from the primigravid group), reduction in episiotomy rates and assisted deliveries. However, there is an increased risk blood loss greater than 500 mL and there may be an increased risk of second degree tears, though we cannot be certain of this. In view of the variable risk of bias of the trials reviewed, further trials using well-designed protocols are needed to ascertain the true benefits and risks of various birth positions.

Video consultations in reproductive medicine: Safety, feasibility and patient satisfaction.

OBJECTIVE: To study the safety and feasibility of virtual consultations in reproductive medicine. DESIGN: This was a descriptive cross-sectional study involving subfertile patients attending a video consultation between September 2021 and August 2022. Clinicians conducting virtual consultations during the same period responded to a parallel survey for healthcare professionals. SETTING: University Hospital in Manchester, UK. PARTICIPANTS: Subfertile patients attending a virtual consultation. Healthcare professionals conducting virtual consultations. INTERVENTION: The survey link was offered in 4,932 consultations. A total of 577 (11.69%) patients responded and 510 completed the questionnaire (88.3%). MAIN OUTCOME MEASURES: Patient satisfaction measured as the percentage of patients preferring virtual to in person consultations. RESULTS: The majority of the patients (475, 91.70%) had a positive experience with the video consultation and just under half of the patients (152, 48.65%) preferred a video consultation to an in person consultation due to cost and time savings. Most patients (375, 72.68%) felt safer and less exposed to COVID-19. When the risk of COVID-19 subsides, 242 patients (47%) would still prefer to attend video consultations, while 169 (32.82%) had no preference. Analysis of the responses from patients reporting a negative experience identified technical problems as a possible cause. The virtual consultations appeared to be suitable for patients with disabilities. The clinicians' survey identified potential legal and ethical concerns. CONCLUSION: Virtual consultations are a safe and feasible alternative to in person consultations for subfertile patients. This large cross-sectional study revealed a high rate of patient satisfaction. Appropriate patient selection accounting for IT literacy, English language understanding and preference is crucial for successful virtual consultations. Further consideration should be given to ethical and legal challenges of virtual consultations. TRIAL REGISTRATION: Research Registry, UIN 6912, https://www.researchregistry.com/browse-the-registry.

Non-coding RNAs-mediated environmental surveillance determines male fertility in plants.

Plants are continuously exposed to environmental stresses leading to significant yield losses. With the changing climatic conditions, the intensity and duration of these stresses are expected to increase, posing a severe threat to crop productivity worldwide. Male gametogenesis is one of the most sensitive developmental stages. Exposure to environmental stresses during this stage leads to male sterility and yield loss. Elucidating the underlying molecular mechanism of environment-affected male sterility is essential to address this challenge. High-throughput RNA sequencing studies, loss-of-function phenotypes of sRNA biogenesis genes and functional genomics studies with non-coding RNAs have started to unveil the roles of small RNAs, long non-coding RNAs and the complex regulatory interactions between them in regulating male fertility under different growth regimes. Here, we discuss the current understanding of the non-coding RNA-mediated environmental stress surveillance and regulation of male fertility in plants. The candidate ncRNAs emerging from these studies can be leveraged to generate environment-sensitive male sterile lines for hybrid breeding or mitigate the impact of climate change on male fertility, as the situation demands.

Prediction of significant OHSS by ovarian reserve and ovarian response - implications for elective freeze-all strategy.

Ovarian Hyperstimulation Syndrome (OHSS) remains a risk to women undergoing assisted conception despite available preventative measures, which are usually applied on the basis of ovarian response. We performed a retrospective cohort study with robust ascertainment of OHSS cases in women undergoing treatment using GnRH antagonist. FSH dose was based on Anti-Mullerian Hormone concentration. A total of 1492 cycles were carried out over 18 months. Moderate/severe OHSS occurred in 24 cycles (1.6%). AMH of 35 pmol/L and/or AFC of 20 or more identified 18/24 (76%) OHSS cases. The optimal thresholds for predicting OHSS were 22.5 pmol/L for AMH (sensitivity 87.5%, specificity 60.6%), 19.5 for AFC (sensitivity 70.8%, specificity 67%), and 9.5 for egg numbers (sensitivity 83.5%, specificity 62.7%). Peak oestradiol levels had no predictive value. The utility of egg number is limited as it is only known after the ovulatory trigger has been administered. Thus, ovarian reserve parameters are better than ovarian response at predicting the risk of significant OHSS in GnRH antagonist cycles in modern clinical practice. Patients with a high ovarian reserve are at risk of OHSS even if their ovarian response is not excessive. Decisions about preventative measures should be based on ovarian reserve rather than ovarian response.

Varicella Zoster in pregnancy.

Chickenpox during pregnancy can cause serious complications for both mother and fetus. This includes varicella pneumonia in the mother, fetal varicella syndrome and varicella of newborn. Primary prevention includes vaccination against varicella infection and is part of standard childhood immunisation programme in many countries. Timely post-exposure prophylaxis of susceptible pregnant women with varicella zoster immunoglobulin is key to preventing chickenpox during pregnancy and its adverse fetomaternal sequelae. Antiviral therapy and appropriate supportive treatment improve maternal and neonatal outcomes.

A meta-analysis on the prevalence of depression in perimenopausal and postmenopausal women in India.

INTRODUCTION: The mental health of perimenopausal and postmenopausal women is a relatively understudied area. This review formally explores the prevalence of depression in perimenopausal and postmenopausal women in India. METHODS: Databases like PubMed, Embase, Cochrane library, Web of Science and Scopus were systematically searched for cross-sectional or cohort studies, providing prevalence of depression in Indian perimenopausal and postmenopausal women. Systematic study selection and data extraction procedures were followed. Quality assessment of individual study was done using AXIS tool. For pooling of effect sizes, the random effects model was used. Funnel plot and Egger's test were used to ascertain publication bias. Subgroup analyses and meta-regression analysis were used to explore heterogeneity in the summary estimates. RESULTS: After a thorough search, ten studies were found to be eligible and included in this review. Pooled estimate for prevalence of depression (random effects model) in perimenopausal and postmenopausal women in India is 42.47 % (95 % CI: 28.73-57.49, I2 = 97.7 %). On visual inspection of the funnel plot and interpreting egger's test (bias: 3.49, SE bias: 3.68, p = 0.37), there was absence of publication bias. CONCLUSION: We documented 42.47 % pooled prevalence of depression in perimenopausal and postmenopausal women in India.

Prevalence of Hypothyroidism in Pregnant Women in India: A Meta-Analysis of Observational Studies.

INTRODUCTION: This meta-analysis was conducted to estimate the prevalence of hypothyroidism among pregnant women in India. METHODS: We searched PubMed, Web of Science, Scopus, Google Scholar, and Shodhganga (Indian thesis repository) for observational studies, providing prevalence of hypothyroidism among pregnant women in India. Systematic study selection and data extraction procedures were followed. Quality assessment of each study was done using JBI critical appraisal checklist. The random effects model was used for pooling the effect sizes. Publication bias was assessed using the funnel plot and rank correlation test. I 2 statistics was used to measure heterogeneity across the studies. Heterogeneity in the pooled estimates was further explored with subgroup analyses and meta-regression analysis. RESULTS: Sixty-one studies were found eligible and included in this review. The pooled estimate of the prevalence of hypothyroidism in pregnant women was 11.07% (95% CI: 8.79-13.84, I 2 = 99%). Pooled prevalence estimates of subclinical and overt hypothyroidism are 9.51% (95% CI: 7.48-12.04, I 2 = 98%) and 2.74% (95% CI: 2.08-3.58, I 2 = 94%). CONCLUSION: We documented 11.07% pooled prevalence of hypothyroidism in pregnant women in India.

Toxoplasmosis in pregnancy.

Toxoplasmosis is one of the common chronic infections caused by the parasite Toxoplasma gondii. Even though its infection in healthy non-pregnant women is self-limited and largely asymptomatic, the main concern is the risk to the fetus by vertical transmission in pregnancy. Congenital toxoplasmosis can result in permanent neurological damage and even serious morbidity such as blindness. Screening programs are implemented in various countries depending on the prevalence and virulence of the parasite in the respective regions. Upon diagnosis of infection, appropriate antibiotic therapy should be initiated as it has been proven to reduce the risk of fetal transmission. Primary prevention remains the key intervention to avoid the infection and hence patient education is an important aspect of the management.

T-shaped Uterus in the 21st Century (Post DES era) - We Need to Know More!

T-Shaped uterus is a rare uterine malformation, and has classically been associated with "in-utero" exposure of DES (diethylstilbestrol). Surprisingly, the prevalence of T shaped uterus is significant even today. Hysteroscopic metroplasty is a simple procedure which can potentially improve outcomes in sub-fertile women, but the data is not robust. There is a need for centralised database for registration of women with T shaped uterine anomalies, which will help in defining clear diagnostic criteria, surgical indication & technique, and follow up of reproductive outcomes after the procedure.

Patient counselling and consent.

To the patient, illness entails not only the physical discomfort but all the psychological, social and emotional ramifications. Patient autonomy and choice are now an integral part of patient care pathways. There has been a steady shift in patient counselling and consent towards supporting patient autonomy over medical paternalism. Patients should be the prime decision makers but they can only do this if they are fully informed. The ultimate and desired goal for the health care teams is to provide a high quality clinical service, which is consistent with evidence based guidelines.

Quantification of Peri-partum Blood Loss: Training Module and Clot Conversion Factor.

OBJECTIVES: To design an objective and accurate method to assess the peri-partum blood loss and to document the benefits of using this method on estimation of blood loss by healthcare professionals. MATERIALS AND METHODS: This prospective study was conducted over 6 months at Cama Albless Hospital, Mumbai. To quantify the loss of liquid blood and clots, we made use of plastic drapes, measuring jars, gravimetric method and a training module along with novel clot conversion factor which was designed to validate the visual assessment of blood loss by healthcare professionals. RESULTS AND CONCLUSION: The visual assessment of blood loss is unreliable. Training module should be on display in labor room and periodic training sessions on visual assessment by and for healthcare professionals are recommended, as we documented that training has definitely a beneficial impact on visual assessment. Clot conversion factor calculated in this study can prove to be a useful tool for objective assessment. Routine use of quantitative measurement rather than visual assessment of blood loss will go a long way to prevent hemorrhage-related maternal deaths.