Biosimilars versus the originator of follitropin alfa for ovarian stimulation in ART: a systematic review and meta-analysis.

Study Question: Is the probability of pregnancy different between women using biosimilars versus the originator of follitropin alfa for ovarian stimulation in ART?

Summary Answer: Meta-analysis of eight randomized clinical trials (RCTs) suggests that live birth, clinical, and ongoing pregnancy rates are significantly lower with biosimilars of follitropin alfa compared to the originator.

What Is Known Already: All biosimilars of follitropin alfa have received regulatory approval by demonstrating non-inferiority in the number of retrieved oocytes compared to the originator. Nevertheless, the most clinically relevant outcome in ART for both clinicians and patients is live birth.

Perinatal and infant outcomes after assisted reproductive technology treatment for endometriosis alone compared with other causes of infertility: a data linkage cohort study.

Objective: To evaluate whether perinatal and infant outcomes differ between singleton births after assisted reproductive technology (ART) in women with endometriosis alone and those with other causes of infertility.

Design: Population-based data linkage cohort study.

Patients: A total of 29,152 ART-conceived singleton births from 24,116 mothers, 2010-2017, New South Wales, Australia.

Deep learning versus manual morphology-based embryo selection in IVF: a randomized, double-blind noninferiority trial.

To assess the value of deep learning in selecting the optimal embryo for in vitro fertilization, a multicenter, randomized, double-blind, noninferiority parallel-group trial was conducted across 14 in vitro fertilization clinics in Australia and Europe. Women under 42 years of age with at least two early-stage blastocysts on day 5 were randomized to either the control arm, using standard morphological assessment, or the study arm, employing a deep learning algorithm, intelligent Data Analysis Score (iDAScore), for embryo selection. The primary endpoint was a clinical pregnancy rate with a noninferiority margin of 5%.

Estimating the impact of bias in causal epidemiological studies: the case of health outcomes following assisted reproduction.

Researchers interested in causal questions must deal with two sources of error: random error (random deviation from the true mean value of a distribution), and bias (systematic deviance from the true mean value due to extraneous factors). For some causal questions, randomization is not feasible, and observational studies are necessary. Bias poses a substantial threat to the validity of observational research and can have important consequences for health policy developed from the findings.

A critical systematic review and meta-analyses of risk factors for fertility problems in a globalized world.

Globally, fertility awareness efforts include well-established risk factors for fertility problems. Risks disproportionately affecting women in the Global South, however, are neglected. To address this gap, we conducted a systematic review and meta-analyses of relevant risk factors to examine the association between risk factors and fertility problems.

Risk for Congenital Anomalies in Children Conceived With Medically Assisted Fertility Treatment : A Population-Based Cohort Study.

Background: More than 2 million children are conceived annually using assisted reproductive technologies (ARTs), with a similar number conceived using ovulation induction and intrauterine insemination (OI/IUI). Previous studies suggest that ART-conceived children are at increased risk for congenital anomalies (CAs). However, the role of underlying infertility in this risk remains unclear, and ART clinical and laboratory practices have changed drastically over time, particularly there has been an increase in intracytoplasmic sperm injection (ICSI) and cryopreservation.

The role of endometrial scratching prior to in vitro fertilization: an updated systematic review and meta-analysis.

Research Question: To evaluate the role of endometrial scratching performed prior to an embryo transfer cycle on the probability of pregnancy compared to placebo/sham or no intervention.

Design: A computerized literature (using a specific search strategy) search was performed across the databases MEDLINE, EMBASE, COCHRANE CENTRAL, SCOPUS and WEB OF SCIENCE up to June 2023 in order to identify randomized controlled trials (RCTs) evaluating the effect of endometrial scratching prior to an embryo transfer cycle on the probability of pregnancy, expressed either as live birth, ongoing pregnancy or clinical pregnancy (in order of significance) compared to placebo/sham or no intervention. Data were pooled using random-effects or fixed-effects model, depending on the presence or not of heterogeneity.

The HERA (Hyper-response Risk Assessment) Delphi consensus for the management of hyper-responders in in vitro fertilization.

Purpose: To provide agreed-upon guidelines on the management of a hyper-responsive patient undergoing ovarian stimulation (OS) METHODS: A literature search was performed regarding the management of hyper-response to OS for assisted reproductive technology. A scientific committee consisting of 4 experts discussed, amended, and selected the final statements. A priori, it was decided that consensus would be reached when ≥66% of the participants agreed, and ≤3 rounds would be used to obtain this consensus.

Childbirth timing and completed family size by the mode of conception-the role of medically assisted reproduction: a population-based cohort study in Australia.

Background: With declining total fertility rates to below replacement levels amongst all high-, middle- and low-income countries, coupled with increasing use of medically assisted reproduction (MAR) treatments globally, we describe the impact of these treatments on completed family size and childbearing timing in a country with unlimited publicly funded access to MAR.

Methods: We utilised a unique longitudinal propensity score-weighted population-based birth cohort that included nulliparous mothers who gave birth after all major forms of MAR treatments (assisted reproductive technologies [ART], ovulation induction [OI], and intrauterine insemination [IUI]) and after natural conception (reference category) in Australia, 2003-2017. We followed first-time mothers over their reproductive lifespan (15-50 years).

Serum anti-müllerian hormone (AMH) concentration during pregnancy: a longitudinal study.

A prospective longitudinal cohort study aimed to longitudinally examine the kinetics of Anti-müllerian hormone (AMH) during the first two trimesters of pregnancy. Pregnant women with stored 1st trimester serum samples were recruited at 24-28 weeks gestation during their gestational diabetes testing, where they provided an additional serum sample. The samples were analysed for AMH, oestradiol and progesterone concentrations.

Freeze-all embryos during treatment with assisted reproduction: Health economic aspects.

Assisted reproductive technologies are evolving, with the most recent example being the introduction of the freeze-all policy during which a fresh embryo transfer does not take place and all embryos of good quality are cryopreserved to be used in future frozen embryo transfers. As the freeze-all policy is becoming more prevalent, it is important to review the economic aspects of this approach, along with considerations of efficacy and safety, and the role of emerging freeze-all-specific ovarian stimulation strategies. Based on the available evidence, the freeze-all policy presents distinct clinical advantages, particularly for high responders.

What is the optimal GnRH antagonist protocol for ovarian stimulation during ART treatment? A systematic review and network meta-analysis.

Background: Several GnRH antagonist protocols are currently used during COS in the context of ART treatments; however, questions remain regarding whether these protocols are comparable in terms of efficacy and safety.

Objective And Rationale: A systematic review followed by a pairwise and network meta-analyses were performed. The systematic review and pairwise meta-analysis of direct comparative data according to the PRISMA guidelines evaluated the effectiveness of different GnRH antagonist protocols (fixed Day 5/6 versus flexible, ganirelix versus cetrorelix, with or without hormonal pretreatment) on the probability of live birth and ongoing pregnancy after COS during ART treatment.

Inter- and Intra-Observer Agreement Between Embryologists for Cytoplasmic String Assessment in Day 5/6 Human Blastocysts.

To investigate inter- and intra-observer agreement in the assessment of cytoplasmic string (CS) by embryologists on day 5/6 human blastocysts using the EmbryoViewer software. This was a prospective study involving five embryologists working between 2019 and 2020. Inter-observer agreement was calculated using assessments performed on 104 day 5/6 blastocysts regarding the presence, number, and location of CS and CS vesicle activity using timelapse videos.

Detailed analysis of cytoplasmic strings in human blastocysts: new insights.

The aim of this study was to determine if there was an association between the presence of cytoplasmic strings (CS) and their characteristics, with blastocyst quality, development and clinical outcome in human blastocysts. This two-centre cohort study was performed between July 2017 and September 2018 and involved a total of 1152 blastocysts from 225 patients undergoing fertilization (IVF) and intracytoplasmic sperm injection (ICSI). All embryos were cultured in Embryoscope+ and were assessed for CS using time-lapse images.

Biosimilars versus the originator of follitropin alfa: Randomized controlled trials are still the best way to evaluate their comparative effectiveness in assisted reproduction.

Biosimilars of follitropin alfa have been introduced in many countries as more affordable alternatives to the reference product for patients undergoing ovarian stimulation for assisted reproductive technology cycles. A recent meta-analysis, by reviewing available evidence originating from randomised controlled trials, has shown that based on the best available evidence, biosimilars of follitropin alfa are associated with lower live birth, ongoing and clinical pregnancy rates compared to the reference product. A subsequently published opinion paper challenges the methodology and results of this meta-analysis and suggests that these data should be ignored.

Is there an optimal window of time for transferring single frozen-thawed euploid blastocysts? A cohort study of 1170 embryo transfers.

Study Question: Is there an optimal window of time when the transfer of single frozen-thawed euploid blastocysts is associated with a maximal live birth rate (LBR)?

Summary Answer: Performing a single frozen-thawed euploid blastocyst transfer at 160 ± 4 h post-hCG trigger in modified-natural frozen-thawed embryo transfer (FET) cycles was independently associated with a higher LBR as compared to transfers outside this window; however, in natural FET cycles, LBRs were comparable across a wider range of time intervals.

What Is Known Already: There is compelling evidence for maintaining embryo-endometrial synchrony to optimize clinical outcomes following FETs, which could potentially be achieved by matching the transfer time of an embryo post-ovulation to its developmental age post-oocyte retrieval. For modified-natural cycles, ovulation is widely accepted to occur ∼40 h following the hCG trigger, whilst ovulation following spontaneous LH surge onset is thought to vary from 24 to 56 h.

dividual participant data meta-analysis of trials comparing rzen versus fesh ebryo transfer strategy (INFORM): a protocol.

Introduction: Existing randomised controlled trials (RCTs) comparing a freeze-all embryo transfer strategy and a fresh embryo transfer strategy have shown conflicting results. A freeze-all or a fresh transfer policy may be preferable for some couples undergoing in-vitro fertilisation (IVF), but it is unclear which couples would benefit most from each policy, how and under which protocols. Therefore, we plan a systematic review and individual participant data meta-analysis of RCTs comparing a freeze-all and a fresh transfer policy.

Pro: Fresh versus frozen embryo transfer. Is frozen embryo transfer the future?

Embryo cryopreservation has been an integral part of ART for close to 40 years and vitrification has boosted overall ART efficacy and safety. Recently, there has been a vivid scientific discussion on whether elective cryopreservation of all embryos (freeze-all) should be pursued for most patients, with a fresh embryo transfer taking place only in selected cases. In terms of efficacy, the available evidence suggests that the freeze-all strategy leads to higher live birth rates after the first embryo transfer compared to the conventional strategy in high responders, while there is no difference in normal responders.

Originator recombinant human follitropin alfa versus recombinant human follitropin alfa biosimilars in Spain: A cost-effectiveness analysis of assisted reproductive technology related to fresh embryo transfers.

This study compared the cost per live birth and cost-effectiveness of the originator recombinant human follicle-stimulating hormone follitropin alfa (r-hFSH-alfa) and r-hFSH-alfa biosimilars for ovarian stimulation prior to assisted reproductive technology treatment in Spain. A decision tree model was developed, comprising pregnancy and live birth for one treatment cycle with fresh embryo transfer. Clinical inputs were based on a recent meta-analysis by Chua et al.

A bespoke data linkage of an IVF clinical quality registry to population health datasets; methods and performance.

Introduction: Assisted reproductive technologies (ART), such as in-vitro fertilisation (IVF), have revolutionised the treatment of infertility, with an estimated 8 million babies born worldwide. However, the long-term health outcomes for women and their offspring remain an area of concern. Linking IVF treatment data to long-term health data is the most efficient method for assessing such outcomes.