The Relationship between Number of Supernumerary Blastocysts Cryopreserved and Probability of a Live Birth Outcome after Single Fresh Blastocyst Transfer: Analysis of over 10 Thousand Cycles.

The ability to predict the likelihood of a live birth after single fresh embryo transfer is an important part of fertility treatment. While past studies have examined the likelihood of live birth based on the number of oocytes retrieved and cleavage-stage embryos available, the odds of a live birth based on the number of supernumerary blastocysts cryopreserved following a fresh embryo transfer has not been rigorously studied. We performed a retrospective analysis, stratified by age, on patients undergoing their first fresh autologous single day 5 blastocyst transfer to assess relationship between the likelihood of a live birth and number of supernumerary blastocysts cryopreserved. In patients aged <35 years and 35-39 years old, the likelihood of a live birth increased linearly between 1 and 6 supplementary blastocysts and non-linearly if 10 or more blastocysts were cryopreserved. When aged 40 years and above, the likelihood of a live birth increased linearly up to 4 cryopreserved blastocysts and then non-linearly if 10 or more blastocysts were cryopreserved. The present study demonstrated a non-linear relationship between the number of supernumerary blastocysts cryopreserved and the likelihood of a live birth after single blastocyst transfer in the first autologous fresh IVF/ICSI cycle across different age groups.

Outcomes of Social Egg Freezing: A Cohort Study and a Comprehensive Literature Review.

The purpose of this study is to evaluate the live birth outcome following oocyte thaw in women who underwent social egg freezing at Guy's Hospital, alongside a detailed published literature review to compare published results with the current study. A retrospective cohort study was conducted between January 2016 and March 2022 for all women who underwent egg freezing during this period. Overall, 167 women had 184 social egg freezing cycles. The mean age at freeze was 37.1 years and an average of 9.5 eggs were frozen per retrieval. In total, 16% of the women returned to use their frozen eggs. The mean egg thaw survival rate post egg thaw was 74%. The mean egg fertilisation rate was 67%. The pregnancy rate achieved per embryo transfer was 48% and the live birth rate per embryo transfer was 35%. We also noted that irrespective of age at freezing, a significantly high live birth rate was achieved when the number of eggs frozen per patient was 15 or more. Despite the rapid increase in social egg freezing cycles, the utilisation rate remains low. Pregnancy and live birth rate post thaw are encouraging if eggs are frozen at a younger age and if 15 eggs or more were frozen per patient.

Comparing endometrial preparation methods in frozen embryo transfers - Does a previous live birth make a difference?

RESEARCH QUESTION: Does the outcome of a medicated or natural endometrial preparation for a frozen cycle differ if a patient has previously experienced a failed fresh cycle? DESIGN: Retrospective matched case-controlled study to investigate frozen embryo transfer (FET) outcomes in women undergone medicated or natural endometrial preparation, with adjustment to the history of previous live birth. 878 frozen cycles were included for analysis, over a period of 2 years. RESULTS: After adjusting for the number of embryos transferred, endometrial thickness and the number of previous embryo transfers, there was no difference in live birth rate (LBR) between medicated-FET and natural-FET groups regardless of the previous fertility outcome (p = 0.08). CONCLUSIONS: A previous live birth does not affect the outcome of a subsequent frozen cycle, regardless of whether medicated- or natural endometrial preparation is used.

Current perspectives on social oocyte freezing.

Demand for oocyte freezing in absence of a medical indication is growing as women delay childbirth and seek to extend the window of opportunity for parenthood. The optimum age for oocyte freezing is below 35 years, whereas currently the mean age of women undergoing oocyte freezing in the UK is 38 years. Nearly half of women undergoing oocyte freezing are not in a relationship. The treatment is not publicly funded and the average price for a complete oocyte freezing and thawing cycle, including annual storage fees, could reach over £7000. The live birth rate per oocyte thaw cycle is 18% and is influenced by age at the time of oocyte freezing. Women considering social oocyte freezing should be thoroughly counselled about the efficacy, limitations, cost implications and alternatives to oocyte freezing and provided with the appropriate support to enable a truly informed reproductive choice.

Cumulative outcome of pre-implantation genetic diagnosis for sickle cell disease: a 5-year review.

To review the cumulative outcome of pre-implantation genetic diagnosis (PGD) cycles performed for prevention of sickle cell disease (SCD). Couples referred for PGD for SCD between April 2012 and October 2017 were included. Ovarian stimulation was performed using a short gonadotrophin-releasing hormone (GnRH) antagonist protocol and follicle-stimulating hormone injections. The GnRH agonist was used to trigger oocyte maturation. Oocytes were fertilised using intracytoplasmic sperm injection. Trophectoderm biopsy was performed on day 5 or 6 followed by vitrification. Genetic testing was done using pre-implantation genetic haplotyping. A total of 60 couples started 70 fresh PGD cycles (mean 1·2 cycles/couple) and underwent a total of 74 frozen-embryo-transfer (FET) cycles (mean 1·3 FET/couple). The mean (SD) female age was 33 (4·4) years and the mean (SD) anti-müllerian hormone level was 22·9 (2·8) pmol/l. The cumulative live-birth rate was 54%/PGD cycle started and 63%/couple embarking on PGD. The rate of multiple births was 8%. The cumulative outcome of PGD treatment for prevention of SCD transmission is high and PGD treatment should be offered to all at-risk couples.

Peri-operative morbidity and fertility outcome after repeat abdominal myomectomy for large fibroid uterus.

This was a retrospective cohort study evaluating peri-operative morbidity of 66 women who underwent repeat abdominal myomectomy compared with 200 women who had primary myomectomy in the same period, matched for age and uterine size. We report the reproductive outcome of women seeking fertility after repeat myomectomy. More pre-operative GnRH analogues were used and midline abdominal skin incision performed in the repeat myomectomy group. The likelihood of major complication was three times higher in the repeat abdominal myomectomy group (OR 3.0, 95% CI 1.67-5.5, p < .001). There was a significantly longer mean hospital stay (p < .01), higher incidence of bleeding (p < .01) and urinary or wound infection (p < .01) in the repeat abdominal myomectomy group. Of the 47 women who had repeat myomectomy for fertility reasons, six women conceived and two live birth at term (4%). Our study highlights the significant peri-operative morbidity and poor subsequent live birth rate associated with repeat abdominal myomectomy.Impact statementWhat is already known on this subject? Repeat abdominal myomectomy is a major surgical procedure with significant morbidity. However, abdominal myomectomy for large fibroid uterus remains the preferred treatment method for women who wish to preserve fertility. Sufficient evidence related to the peri-operative morbidity and fertility outcome after repeat abdominal myomectomy is lacking.What do the results of this study add? This is the largest study reporting peri-operative morbidity and pregnancy outcome following repeat abdominal myomectomy. Our results highlight the three times increased risk of major complications associated with repeat abdominal myomectomy compared to primary myomectomy with the poor subsequent live birth rate.What are the implications of these findings for clinical practice and/or further research? Our study complements the sparse existing data on the outcome of repeat abdominal myomectomy and underscore the potentially significant peri-operative morbidity and poor subsequent live birth rate associated with the procedure. This information should be used in counselling women with fibroid recurrence after primary myomectomy before they embark on repeat surgery.

A narrative review of adjuvants in in vitro fertilisation: evidence for good clinical practice.

A review of studies published between January 1, 1984 and January 31, 2019 was performed with the aim of analysing the efficacy and adverse effects of commonly used adjuvants to in vitro fertilisation. The authors preferentially selected recent systematic reviews and randomised control trials (where available) from an electronic literature search. The review showed that low molecular weight heparin, corticosteroids and embryo glue may be of use in selected patient groups. Other adjuncts (such as growth hormone, assisted hatching, endometrial disruption and dehydroepiandrosterone) cannot currently be recommended as collated results showed no overall benefit to clinical pregnancy rates or live birth rates. There is a significant lack of robust evidence in this field, and areas in particular need of further research have been highlighted. In conclusion, caution should be exercised in prescribing adjuvants in in vitro fertilisation, either individually or in combination as further research is needed to ascertain their efficacy. Many adjuvants carry the risk of adverse effects which should also be considered. Patients should be clearly informed of the evidence, and where it is lacking, for these treatments. There is a need for further good quality trials to address the questions regarding best practice.

Early oocyte denudation does not compromise ICSI cycle outcome: a large retrospective cohort study.

This retrospective cohort study of 2051 consecutive fresh non-donor intracytoplasmic sperm injection (ICSI) cycles investigated whether time from oocyte retrieval to denudation, precisely measured and recorded by an operator-independent automated radiofrequency-based system, affected cycle outcome. ICSI cycles were divided into two groups: group I (denudation within <2 h of oocyte retrieval, n = 1118) and group II (denudation 2-5 h after oocyte retrieval, n = 933). Univariate analysis by two-sample t-test or Mann-Whitney test was used, as appropriate. Both groups were comparable with regards to mean number of oocytes retrieved and fertilized normally after ICSI. The mean number of embryos transferred and surplus embryos cryopreserved at the blastocyst stage were similar. There was no significant difference in fertilization, embryo implantation, pregnancy, clinical pregnancy or live birth rates between the groups. Analysis of group I ICSI outcome after subdivision into immediate (up to 30 min) and early (31-119 min) denudation showed no statistically significant differences between the two subgroups. In conclusion, early oocyte denudation within <2 h after retrieval does not appear to compromise ICSI cycle outcome, permitting more efficiency and flexibility in scheduling laboratory workload. As this was a retrospective observational study, further prospective studies are required to confirm the findings.

Effect of male body mass index on assisted reproduction treatment outcome: an updated systematic review and meta-analysis.

Men with a body mass index (BMI) of 30 or over are more likely to have reduced fertility and fecundity rates. This systematic review and meta-analysis evaluated the effect of male BMI on IVF and intracytoplasmic sperm injection (ICSI) outcome. An electronic search for published literature was conducted in MEDLINE and EMBASE between 1966 and November 2016. Outcome measures were clinical pregnancy rates (CPR) and live birth rates (LBR) per IVF or ICSI cycle. Eleven studies were identified, including 14,372 cycles; nine reported CPR and seven reported LBR. Pooling of data from those studies revealed that raised male BMI was associated with a significant reduction in CPR (OR 0.78, 95% CI 0.63 to 0.98, P = 0.03) and LBR (OR 0.88, 95% CI 0.82 to 0.95, P = 0.001) per IVF-ICSI treatment cycle. Male BMI could be an important factor influencing IVF-ICSI outcome. More robust studies are needed to confirm this conclusion using standardized methods for measuring male BMI, adhering to the World Health Organization definitions of BMI categories, accounting for female BMI, IVF and ICSI cycle characteristics, including the number of embryos transferred and embryo quality, and use the live birth rate per cycle as primary outcome.

Impact of the outcome of fresh blastocyst transfer on the subsequent frozen-thawed blastocyst transfer cycle.

The objective of this observational study was to assess the influence of the outcome of fresh blastocyst transfer on the success rate of the subsequent sibling frozen-thawed blastocyst transfer (FBT) cycle. In total, 1639 FBT cycles were divided into two groups: Group A (n = 698) cycles in which a positive pregnancy test result was achieved and Group B (n = 941) cycles in which no pregnancy was achieved in the preceding fresh IVF cycle. Mean age at cryopreservation, basal FSH level, number of oocytes retrieved, number of embryos transferred in the fresh cycle and survival rate of the thawed blastocysts in the FBT cycle were comparable between the two groups. Although significantly more thawed blastocysts were transferred in the FBT cycles in Group B compared with Group A, the live birth rate in Group A was significantly higher compared with Group B. After adjusting for potentially confounding variables, the likelihood of a live birth after FBT was significantly higher when a pregnancy was achieved in the preceding fresh IVF cycle. Achieving a pregnancy after fresh blastocyst transfer is an independent factor influencing the outcome of the subsequent sibling FBT.

An update on the prevention of ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome is a potentially life-threatening, but preventable iatrogenic complication of in vitro fertilisation treatment. In recent years, new strategies have been developed to minimise the risk of ovarian hyperstimulation syndrome after in vitro fertilisation, including better at-risk patient identification prior to starting treatment, the use of a lower human chorionic gonadotrophin dose or alternative medication instead of human chorionic gonadotrophin to induce final oocyte maturation such as gonadotrophin-releasing hormone agonist and kisspeptin in antagonist cycles, cryopreservation of all embryos and delayed embryo transfer, and the use of oral dopamine agonists after oocyte retrieval. In this article, the advantages and limitations of those new developments are discussed and future directions towards establishment of an ovarian hyperstimulation syndrome-free in vitro fertilisation clinic are explored.

Outcome of preimplantation genetic diagnosis using FISH analysis for recurrent miscarriage in low-risk reciprocal translocation carriers.

OBJECTIVE: To assess PGD outcome using FISH analysis in couples with a history of recurrent miscarriage associated with a parental carrier of reciprocal translocation. STUDY DESIGN: Couples in whom one partner was a carrier of a reciprocal translocation and had a history of two or more miscarriages and a low risk of a live born offspring with an unbalanced chromosomal rearrangement, underwent PGD treatment between 2000 and 2012. RESULTS: 91 couples started 171 fresh and 11 frozen PGD cycles. Of the fresh cycles, 162 (95%) reached oocyte retrieval and 107 (63%) had embryo transfer. In 14 cycles (8%), surplus embryos were cryopreserved. Pregnancy was achieved in 52 fresh PGD cycles, leading to 20 miscarriages and 32 live births. Eleven frozen embryo transfer cycles resulted in two miscarriages and three live births. The overall live birth rate was 19% per fresh and frozen PGD cycle started (35/182) and miscarriage rate was 39% per pregnancy (22/57). The cumulative live birth rate was 32% per couple (29/91). CONCLUSION: After PGD for recurrent miscarriage in low-risk reciprocal translocation carriers, the miscarriage risk remains high and chance of live birth is low. For those translocation carriers, natural conception may be a better option.

Hysteroscopy in recurrent in-vitro fertilisation failure (TROPHY): a multicentre, randomised controlled trial.

BACKGROUND: The success rate of in-vitro fertilisation (IVF) remains low and many women undergo multiple treatment cycles. A previous meta-analysis suggested hysteroscopy could improve outcomes in women who have had recurrent implantation failure; however, studies were of poor quality and a definitive randomised trial was needed. In the TROPHY trial we aimed to assess whether hysteroscopy improves the livebirth rate following IVF treatment in women with recurrent failure of implantation. METHODS: We did a multicentre, randomised controlled trial in eight hospitals in the UK, Belgium, Italy, and the Czech Republic. We recruited women younger than 38 years who had normal ultrasound of the uterine cavity and history of two to four unsuccessful IVF cycles. We used an independent web-based trial management system to randomly assign (1:1) women to receive outpatient hysteroscopy (hysteroscopy group) or no hysteroscopy (control group) in the month before starting a treatment cycle of IVF (with or without intracytoplasmic sperm injection). A computer-based algorithm minimised for key prognostic variables: age, body-mass index, basal follicle-stimulating hormone concentration, and the number of previous failed IVF cycles. The order of group assignment was masked to the researchers at the time of recruitment and randomisation. Embryologists involved in the embryo transfer were masked to group allocation, but physicians doing the procedure knew of group assignment and had hysteroscopy findings accessible. Participants were not masked to their group assignment. The primary outcome was the livebirth rate (proportion of women who had a live baby beyond 24 weeks of gestation) in the intention-to-treat population. The trial was registered with the ISRCTN Registry, ISRCTN35859078. FINDINGS: Between Jan 1, 2010, and Dec 31, 2013, we randomly assigned 350 women to the hysteroscopy group and 352 women to the control group. 102 (29%) of women in the hysteroscopy group had a livebirth after IVF compared with 102 (29%) women in the control group (risk ratio 1·0, 95% CI 0·79-1·25; p=0·96). No hysteroscopy-related adverse events were reported. INTERPRETATION: Outpatient hysteroscopy before IVF in women with a normal ultrasound of the uterine cavity and a history of unsuccessful IVF treatment cycles does not improve the livebirth rate. Further research into the effectiveness of surgical correction of specific uterine cavity abnormalities before IVF is warranted. FUNDING: European Society of Human Reproduction and Embryology, European Society for Gynaecological Endoscopy.

British Fertility Society Policy and Practice Committee: adjuvants in IVF: evidence for good clinical practice.

Optimisation of the environment favourable for satisfactory ovarian response to stimulation and successful embryo implantation remains at the core of assisted conception programmes. The evidence base for the routine use of different adjuvants, alone or in combination, for women undergoing their first in vitro fertilisation (IVF) treatment cycle and for those with poor prognosis is inadequate. The aim of this document is to update the last review of the available literature carried out by the British Fertility Society Policy and Practice Committee (BFS P&P) published in 2009 and to provide fertility professionals with evidence-based guidance and recommendations regarding the use of immunotherapy, vasodilators, uterine relaxants, aspirin, heparin, growth hormone, dehydroepiandrosterone, oestrogen and metformin as adjuvants in IVF. Unfortunately despite the lapse of 5 years since the last publication, there is still a lack of robust evidence for most of the adjuvants searched and large well-designed randomised controlled trials are still needed. One possible exception is metformin, which seems to have a positive effect in women with polycystic ovary syndrome undergoing IVF. Patients who are given other adjuvants on an empirical basis should always be informed of the lack of evidence and the potential side effects.