The composition of commercially available human embryo culture media.

Study Question: What is the composition of currently available commercial human embryo culture media provided by seven suppliers, for each stage of human preimplantation embryo development?

Summary Answer: While common trends existed across brands, distinct differences in composition underlined the absence of a clear standard for human embryo culture medium formulation.

What Is Known Already: The reluctance of manufacturers to fully disclose the composition of their human embryo culture media generates uncertainty regarding the culture conditions that are used for human preimplantation embryo culture. The critical role of the embryo culture environment is well-recognized, with proven effects on IVF success rates and child outcomes, such as birth weight.

Outcomes of female fertility preservation with cryopreservation of oocytes or embryos in the Netherlands: a population-based study.

Study Question: What are the reproductive outcomes of patients who cryopreserved oocytes or embryos in the context of fertility preservation in the Netherlands?

Summary Answer: This study shows that after a 10-year follow-up period, the utilization rate to attempt pregnancy using cryopreserved oocytes or embryos was 25.5% and the cumulative live birth rate after embryo transfer was 34.6% per patient.

The web-based Pleasure&Pregnancy programme in the treatment of unexplained infertility: a randomized controlled trial.

Study Question: Does offering the Pleasure&Pregnancy (P&P) programme rather than expectant management improve naturally conceived ongoing pregnancy rates in couples diagnosed with unexplained infertility?

Summary Answer: The P&P programme had no effect on the ongoing pregnancy rates of couples with unexplained infertility.

What Is Known Already: Underpowered studies suggested that face-to-face interventions targeting sexual health may increase pregnancy rates. The impact of an eHealth sexual health programme had yet to be evaluated by a large randomized controlled trial.

Transgender persons' view on previous fertility decision-making and current infertility: a qualitative study.

Study Question: How do adult transgender and gender diverse (TGD) people, who are infertile due to prior gender-affirming treatment, view their current infertility and their reproductive decisions made in the past?

Summary Answer: In a time where sterilization was mandatory, transgender adolescents prioritized gender-affirming treatment over their future fertility and would make the same choice today despite emotional challenges related to infertility experienced by some.

What Is Known Already: Under transgender law in the Netherlands, sterilization was required for legal gender recognition until 2014, resulting in permanent infertility. The long-term consequences of this iatrogenic infertility in transgender adolescents who have now reached adulthood remain underexplored.

One-third of amenorrheic transmasculine people on testosterone ovulate.

Transmasculine people usually reach amenorrhea within 6 months of adequate testosterone treatment. It is often assumed that no ovulation occurs during amenorrhea. However, in this study, we report recent ovulatory activity in amenorrheic transmasculine people on testosterone therapy at gender-affirming oophorectomy.

Anxiety, depression, and body image among infertile women with and without polycystic ovary syndrome.

Study Question: In women undergoing fertility treatment, do those with polycystic ovary syndrome (PCOS) have a higher prevalence of symptoms of anxiety and depression and lower body appreciation than women without PCOS?

Summary Answer: Having PCOS was not associated with symptoms of anxiety and depression but was associated with somewhat lower body appreciation.

What Is Known Already: PCOS has been associated with a higher chance to develop mental health problems, like anxiety, and body image concerns. The International Guidelines on PCOS recommend that all women with PCOS should routinely be screened for anxiety and depressive disorders.

Reproductive Outcomes of Women with Turner Syndrome Undergoing Oocyte Vitrification: A Retrospective Multicenter Cohort Study.

Background: Turner syndrome (TS) is accompanied with premature ovarian insufficiency. Oocyte vitrification is an established method to preserve fertility. However, data on the oocyte yield in women with TS who vitrify their oocytes and the return rate to utilize the oocytes are scarce.

Human ovarian aging is characterized by oxidative damage and mitochondrial dysfunction.

Study Question: Are human ovarian aging and the age-related female fertility decline caused by oxidative stress and mitochondrial dysfunction in oocytes?

Summary Answer: We found oxidative damage in oocytes of advanced maternal age, even at the primordial follicle stage, and confirmed mitochondrial dysfunction in such oocytes, which likely resulted in the use of alternative energy sources.

What Is Known Already: Signs of reactive oxygen species-induced damage and mitochondrial dysfunction have been observed in maturing follicles, and even in early stages of embryogenesis. However, although recent evidence indicates that also primordial follicles have metabolically active mitochondria, it is still often assumed that these follicles avoid oxidative phosphorylation to prevent oxidative damage in dictyate arrested oocytes.

The role of uterine natural killer cells in recurrent pregnancy loss and possible treatment options.

This narrative review summarizes the current knowledge on the role of uterine natural killer (uNK) cells in recurrent pregnancy loss and possible treatment options. Recurrent pregnancy loss involves 2 or more consecutive miscarriages, affecting around 3% of couples attempting conception. Despite extensive investigation, causes often remain elusive.

Cancer risk in children, adolescents, and young adults conceived by ART in 1983-2011.

Study Question: Do children, adolescents, and young adults born after ART, including IVF, ICSI and frozen-thawed embryo transfer (FET), have an increased risk of cancer compared with children born to subfertile couples not conceived by ART and children from the general population?

Summary Answer: After a median follow-up of 18 years, the overall cancer risk was not increased in children conceived by ART, but a slight risk increase was observed in children conceived after ICSI.

What Is Known Already: There is growing evidence that ART procedures could perturb epigenetic processes during the pre-implantation period and influence long-term health. Recent studies showed (non-)significantly increased cancer risks after ICSI and FET, but not after IVF.

Heparin for women with recurrent miscarriage and inherited thrombophilia (ALIFE2): an international open-label, randomised controlled trial.

Background: Anticoagulant therapy might reduce the number of miscarriages and adverse pregnancy outcomes in women with recurrent pregnancy loss and inherited thrombophilia. We aimed to assess use of low-molecular-weight heparin (LMWH) versus standard care in this population.

Methods: The ALIFE2 trial was an international open-label, randomised controlled trial undertaken in hospitals in the UK (n=26), the Netherlands (n=10), the USA (n=2), Belgium (n=1), and Slovenia (n=1).

Outcomes of oocyte vitrification in trans masculine individuals.

Research Question: What are the outcomes and experiences of oocyte vitrification treatment in trans masculine individuals (TMI) before and after testosterone use?

Design: This retrospective cohort study was conducted at the Amsterdam UMC in the Netherlands between January 2017 and June 2021. The TMI who had completed an oocyte vitrification treatment were consecutively approached for participation. Informed consent was provided by 24 individuals.

A core outcome set for trials in miscarriage management and prevention: An international consensus development study.

Objective: To develop core outcome sets (COS) for miscarriage management and prevention.

Design: Modified Delphi survey combined with a consensus development meeting.

Setting: International.

ESHRE guideline: recurrent pregnancy loss: an update in 2022.

Study Question: What are the updates for the recommended management of women with recurrent pregnancy loss (RPL) based on the best available evidence in the literature from 2017 to 2022?

Summary Answer: The guideline development group (GDG) updated 11 existing recommendations on investigations and treatments for RPL, and how care should be organized, and added one new recommendation on adenomyosis investigation in women with RPL.

What Is Known Already: A previous ESHRE guideline on RPL was published in 2017 and needs to be updated.

Study Design Size Duration: The guideline was developed and updated according to the structured methodology for development and update of ESHRE guidelines.

Long-term outcomes of switching to gonadotrophins versus continuing with clomiphene citrate, with or without intrauterine insemination, in women with normogonadotropic anovulation and clomiphene failure: follow-up study of a factorial randomized clinical trial.

Study Question: What are the long-term outcomes after allocation to use of gonadotrophins versus clomiphene citrate (CC) with or without IUI in women with normogonadotropic anovulation and clomiphene failure?

Summary Answer: About four in five women with normogonadotropic anovulation and CC failure had a live birth, with no evidence of a difference in pregnancy outcomes between the allocated groups.

What Is Known Already: CC has long been used as first line treatment for ovulation induction in women with normogonadotropic anovulation. Between 2009 and 2015, a two-by-two factorial multicentre randomized clinical trial in 666 women with normogonadotropic anovulation and six cycles of CC failure was performed (M-ovin trial).

Expectant management versus IUI in unexplained subfertility and a poor pregnancy prognosis (EXIUI study): a randomized controlled trial.

Study Question: For couples with unexplained subfertility and a poor prognosis for natural conception, is 6 months expectant management (EM) inferior to IUI with ovarian stimulation (IUI-OS), in terms of live births?

Summary Answer: In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of EM is inferior compared to IUI-OS in terms of live births.

What Is Known Already: Couples with unexplained subfertility and a poor prognosis are often treated with IUI-OS. In couples with unexplained subfertility and a relatively good prognosis for natural conception (>30% in 12 months), IUI-OS does not increase the live birth rate as compared to 6 months of EM.

Development of the OPAL prediction model for prediction of live birth in couples with recurrent pregnancy loss: protocol for a prospective and retrospective cohort study in the Netherlands.

Introduction: Recurrent pregnancy loss (RPL) is defined as the loss of two or more conceptions before 24 weeks gestation. Despite extensive diagnostic workup, in only 25%-40% an underlying cause is identified. Several factors may increase the risk for miscarriage, but the chance of a successful pregnancy is still high.

The needs of subfertile couples continuing to attempt natural conception: in-depth interviews.

Study Question: What are the experiences and the support and sexual advice needs of subfertile couples continuing to attempt natural conception after the diagnostic fertility work-up?

Summary Answer: Exploration of the experiences of couples showed that couples would have appreciated fertility clinic staff embedding expectant management into the fertility clinic trajectory, supportive staff with female and male patient interactions and advice on common experiences of peers and on managing their lifestyle, distress and subfertility-related sexual challenges.

What Is Known Already: Dutch and British professional guidelines advise newly diagnosed subfertile couples with a 'good prognosis' to continue to attempt natural conception and do not require fertility clinic staff to interact with patients. Fertility clinic staff and subfertile couples struggle to follow these guidelines as they feel an urgent need for action.

Endometrial thickness assessed by transvaginal ultrasound in transmasculine people taking testosterone compared with cisgender women.

Research Question: What is the endometrial thickness of endometrium exposed to testosterone in transmasculine people compared with unexposed endometrium in cisgender women as determined by transvaginal ultrasound (TVU)?

Design: Single centre, cross-sectional cohort study conducted the Centre of Expertise on Gender Dysphoria in Amsterdam. Between 2013 and 2015, transmasculine people scheduled for gender affirming surgery (GAS) were included in this study after they provided informed consent. They were undergoing gender affirming hormone therapy (testosterone) for at least 1 year.

Fertility preservation for women with breast cancer: a multicentre randomized controlled trial on various ovarian stimulation protocols.

Study Question: Does ovarian stimulation with the addition of tamoxifen or letrozole affect the number of cumulus-oocyte complexes (COCs) retrieved compared to standard ovarian stimulation in women with breast cancer who undergo fertility preservation?

Summary Answer: Alternative ovarian stimulation protocols with tamoxifen or letrozole did not affect the number of COCs retrieved at follicle aspiration in women with breast cancer.

What Is Known Already: Alternative ovarian stimulation protocols have been introduced for women with breast cancer who opt for fertility preservation by means of banking of oocytes or embryos. How these ovarian stimulation protocols compare to standard ovarian stimulation in terms of COC yield is unknown.

Dynamics of reproductive genetic technologies: Perspectives of professional stakeholders.

Reproductive and genetic medicine are evolving rapidly, and new technologies are already impacting current practices. This includes technologies that can identify a couples' risk of having a child with a genetic disorder. Responsible implementation of new technologies requires evaluation of safety and ethics.

Is home-based monitoring of ovulation to time frozen embryo transfer a cost-effective alternative for hospital-based monitoring of ovulation? Study protocol of the multicentre, non-inferiority Antarctica-2 randomised controlled trial.

Study Question: The objective of this trial is to compare the effectiveness and costs of true natural cycle (true NC-) frozen embryo transfer (FET) using urinary LH tests to modified NC-FET using repeated ultrasound monitoring and ovulation trigger to time FET in the NC. Secondary outcomes are the cancellation rates of FET (ovulation before hCG or no dominant follicle, no ovulation by LH urine test, poor embryo survival), pregnancy outcomes (miscarriage rate, clinical pregnancy rates, multiple ongoing pregnancy rates, live birth rates, costs) and neonatal outcomes (including gestational age, birthweight and sex, congenital abnormalities or diseases of babies born).

What Is Known Already: FET is at the heart of modern IVF.