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A randomized, non-inferiority trial on the DuoStim strategy in PGT-A cycles
Is the DuoStim strategy an effective alternative to two conventional ovarian stimulation cycles in poor-prognosis patients undergoing preimplantation genetic testing for aneuploidies (PGT-A) to improve euploidy rates and obtain the first euploid embryo in less time?Concordance of PGT for aneuploidies between blastocyst biopsies and spent blastocyst culture medium
Non-invasive preimplantation genetic testing for aneuploidies (niPGT-A) avoids the possible detrimental impact of invasive PGT-A on embryo development and clinical outcomes. Does cell-free DNA (cfDNA) from spent blastocyst culture medium (BCM) reflect embryonic chromosome status better than trophectoderm (TE) biopsy?Preimplantation genetic testing for human blastocysts with potential parental contamination using a quantitative parental contamination test (qPCT): an evidence-based study
Is it possible to develop a quantitative method for detecting parental DNA contamination in conventional IVF using preimplantation genetic testing for aneuploidy (PGT-A)?Ovulation induction using sequential letrozole/gonadotrophin in infertile women with PCOS: a randomized controlled trial
Polycystic ovary syndrome (PCOS) is the most common ovarian endocrine disease in women of reproductive age (Conway et al., 2014), with an incidence among premenopausal women of up to 20% when applying Rotterdam criteria (Yildiz et al., 2012). Oligo-ovulation is the most important and classic clinical manifestation of PCOS (Escobar-Morreale, 2018), and the resulting infertility is the major cause of anovulatory infertility (Balen and Michelmore, 2002), which affects many infertile women of reproductive age.PGT for structural chromosomal rearrangements in 300 couples reveals specific risk factors but an interchromosomal effect is unlikely
What factors affect the proportion of chromosomally balanced embryos in structural rearrangement carriers? Is there any evidence for an interchromosomal effect (ICE)?Comparison of different endometrial preparation protocols on frozen embryo transfer pregnancy outcome in patients with normal ovulation
What is the effect of letrozole use in patients undergoing frozen embryo transfer (FET) with normal ovulation? Although the number of FETs is increasing, an optimal protocol for FET (particularly vitrified–warmed embryo transfer) is yet to be determined. The aim of this study was to evaluate letrozole use on patients with normal menstrual cycles compared with hormone replacement therapy (HRT) cycles and natural cycles.Supporting first FSH dosage for ovarian stimulation with machine learning
Although significant strides have been made in the last 40 years, the mean pregnancy rate after an IVF cycle still hovers around 30%, with a 20% chance of delivery (De Geyter et al., 2018). An important requisite to the success of an IVF cycle is the availability of a certain number of mature oocytes (metaphase III [MII]); usually obtained after ovarian stimulation.Does the HCG trigger dose used for IVF impact luteal progesterone concentrations? a randomized controlled trial
Is there an association between the ovulation trigger dose of human chorionic gonadotrophin (HCG) and endogenous progesterone production during the luteal phase?Similar fertilization rates and preimplantation embryo development among testosterone-treated transgender men and cisgender women
What are the effects of testosterone treatment on oocyte fertilization and preimplantation embryo development among transgender men who have undergone fertility preservation?Comparison of predictive models for cumulative live birth rate after treatment with ART
Can a machine learning model better predict the cumulative live birth rate for a couple after intrauterine insemination or embryo transfer than Cox regression based on their personal characteristics?Non-invasive embryo selection strategy for clinical IVF to avoid wastage of potentially competent embryos
Can a non-invasive embryo transfer strategy provide a reference for embryo selection to be established?Testicular biopsy for fertility preservation in early-diagnosed Klinefelter patients: patient characteristics and long-term follow-up
Which early-diagnosed Klinefelter syndrome patients have been offered cryopreservation of testicular tissue as part of fertility preservation before spermatogonial stem cell (SSC) loss? Do these Klinefelter syndrome patients present with behavioural, cognitive and/or psychological problems? Does a testicular biopsy procedure have long-term effects on the gonadal development of Klinefelter syndrome patients?Pregnancy, fertility concerns and fertility preservation procedures in a national study of French breast cancer survivors
What are the real-life oncofertility practices in young women diagnosed with breast cancer?Does underlying infertility in natural conception modify the epigenetic control of imprinted genes and transposable elements in newborns?
Does the epigenetic control of imprinted genes and transposable elements at birth differ according to time to conception in natural conception and after intrauterine insemination (IUI)?A meta-analysis of serum lipid profiles in premature ovarian insufficiency
Premature ovarian insufficiency (POI), defined as loss of normal ovarian functions before the age of 40 years, occurs in at least 1% of all women. It affects the reproductive system and causes many health problems and psychological stress. Abnormal serum lipid profile leads to cardiovascular diseases, which are strongly associated with high mortality in patients with POI. To date, several studies have examined the levels of different serum lipids in patients with POI. The results, however, are either inconclusive or inconsistent.A microenvironment of high lactate and low pH created by the blastocyst promotes endometrial receptivity and implantation
Is the blastocyst's idiosyncratic metabolic production of lactate, and creation of a specialized microenvironment at the implatation site, an important mediator of maternal–fetal signalling to promote endometrial receptivity and implantation?Is oxytocin receptor antagonist administration around embryo transfer associated with IVF treatment success? A systematic review and meta-analysis
A systematic literature review and meta-analysis was conducted to evaluate whether the administration of an oxytocin receptor antagonist (OTR-a) around embryo transfer is associated with live birth and pregnancy achievement in IVF treatment. Multiple databases were searched for randomized controlled trials (RCT) comparing the outcome of IVF treatment with administration of an OTR-a before, during or after embryo transfer versus administration of placebo/nil. The literature search identified 11 eligible RCT.Comparison of methods for isolation and quantification of circulating cell-free DNA from patients with endometriosis
Endometriosis is a common oestrogen-dependent benign disease, which is defined by the presence of endometrial-like tissue outside of the uterus. Clinical features associated with endometriosis are chronic pelvic pain, pain during intercourse, dysmenorrhoea and infertility (Bulun, 2009; Burghaus et al., 2019). Endometriosis can be detected in 25–50% of infertile women, and 30–50% of women with endometriosis are infertile (Bulletti et al., 2010). Endometriosis affects the receptivity of the endometrium and the development of the oocyte and embryo, leading to significant lower pregnancy rates by natural conception and by IVF (Barnhart et al., 2002; de Ziegler et al., 2010).Clinical outcomes and utilization from over a decade of planned oocyte cryopreservation
An age-related decline in fertility is a well-known physiologic effect related to decreases in oocyte quantity and quality (ACOG and ASRM, 2014). Older women who conceive naturally have an increased risk of fetal chromosomal abnormalities and pregnancy loss (Spandorfer and Chung, 2004). Despite this association, a global shift towards delayed childbearing has occurred (OECD Family Database, OECD, 2019). Age at first birth and the proportion of pregnancies in women over the age of 35 years have been increasing in the USA since 1980 (Martin et al., 2019).IVF impact on the risk of recurrence of endometrial adenocarcinoma after fertility-sparing management
Do IVF treatments after conservative management of endometrial atypical hyperplasia or grade 1 endometrial adenocarcinoma (AH/EC) increase the risk of disease recurrence?The inhibition of WIP1 phosphatase accelerates the depletion of primordial follicles
What role does wild-type p53-induced phosphatase 1 (WIP1) play in the regulation of primordial follicle development?Lower risk of adverse perinatal outcomes in natural versus artificial frozen–thawed embryo transfer cycles: a systematic review and meta-analysis
Frozen–thawed embryo transfer (FET) has increased steadily worldwide over the past few years (De Geyter et al., 2020; Zegers-Hochschild et al., 2020). In 2015, FET accounted for about 40% of all IVF cycles in Europe (De Geyter et al., 2020). The freeze-all strategy has reported successful results with higher live birth rates and lower incidence of ovarian hyperstimulation syndrome compared with fresh embryo transfer (Roque et al., 2019; Wei et al., 2019). Some studies have suggested that singletons born after FET also have better neonatal outcomes compared with singletons born after fresh embryo transfer, e.g.Whether to transfer mosaic embryos: a cytogenetic view of true mosaicism by amniocentesis
Preimplantation genetic testing for aneuploidies has increasingly been employed for embryo selection, resulting in a recent surge in mosaic embryos. According to the cytogenetic results, which types of mosaic embryo survive early pregnancy, progress to the second trimester and finally result in a live birth?Impact of chronic endometritis in infertility: a SWOT analysis
Chronic endometritis is a pathology often associated with reproductive failure, but there are still no clear recommendations on whether its inclusion in the initial study of infertile couples is necessary. In this discussion paper, based on a SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis, the different aspects of the repercussions of chronic endometritis in fertility are evaluated. To avoid possible subjectivity in the analysis and results of this study, the researchers followed the Oxford criteria for the evaluation of evidence.Influence of ethnicity on different aspects of polycystic ovary syndrome: a systematic review
This systematic review aimed to assess variations in the clinical presentation and treatment outcomes of patients with polycystic ovary syndrome (PCOS) belonging to different ethnicities. A search was performed for studies comparing various clinical aspects of PCOS in two or more different ethnic groups. After screening 2264 studies, 35 articles were included in the final analysis. In comparison with White women with PCOS (wPCOS), East Asian women with PCOS (eaPCOS) were less hirsute, whereas Hispanic women with PCOS (hPCOS), South Asian women with PCOS (saPCOS) and Middle Eastern women with PCOS (mePCOS) were more hirsute.Spatial and temporal changes in follicle distribution in the human ovarian cortex
How does follicle distribution evolve in the human ovarian cortex between the ages of 20 and 35 years?miR-532-3p: a possible altered miRNA in cumulus cells of infertile women with advanced endometriosis
Is the profile of microRNA (miRNA) altered in cumulus cells of infertile women with early (EI/II) and advanced (EIII/IV) endometriosis?An artificial intelligence model based on the proteomic profile of euploid embryos and blastocyst morphology: a preliminary study
The two main factors responsible for the success of an IVF treatment are the endometrium and the embryo (Edwards et al., 1984). Non-invasive methods (morphological and morphokinetic) as well as invasive methods (genetic testing) are currently used in IVF laboratories in embryo selection. However, new approaches to select embryos are still being investigated due to the limited improvement in live birth rate over the last few years (Dyer et al., 2016; De Geyter et al., 2018).Do fertility tracking applications offer women useful information about their fertile window?
To characterize mobile fertility tracking applications (apps) to determine the use of such apps for women trying to conceive by identifying the fertile window.A revolutionary joins the establishment: Reproductive Biomedicine Online turns 20
This commentary highlights the publishing revolution achieved by Robert Edwards in founding Reproductive Biomedicine Online. It corrects some inaccuracies in the account given by Roger Gosden in his recently published book Let There Be Life: An Intimate Portrait of Robert Edwards and His IVF Revolution.Same-sex male couples and single men having children using assisted reproductive technology: a quantitative analysis
How do same-sex male couples (SSMC) and single men perceive their experience of using assisted reproductive technology (ART) in Canada; what factors contribute to their experience and the decisions made throughout the ART process?The prevalence, promotion and pricing of three IVF add-ons on fertility clinic websites
How are IVF clinic websites advertising three common IVF add-ons: assisted hatching, time-lapse embryo imaging and preimplantation genetic testing for aneuploidies (PGT-A)?Empathetic application of machine learning may address appropriate utilization of ART
The value of artificial intelligence to benefit infertile patients is a subject of debate. This paper presents the experience of one aspect of artificial intelligence, machine learning, coupled with patient empathy to improve utilization of assisted reproductive technology (ART), which is an important aspect of care that is under-recognized. Although ART provides very effective options for infertile patients to build families, patients often discontinue ART when further treatment is likely to be beneficial and most of these patients do not achieve pregnancy without medical aid.Candidate genes for age at menarche are associated with endometriosis
Are the candidate genes for age at menarche associated with a risk of endometriosis?The performance of the Elecsys® anti-Müllerian hormone assay in predicting extremes of ovarian response to corifollitropin alfa
What is the performance of anti-Müllerian hormone (AMH) as measured by the Elecsys® AMH assay in predicting ovarian response in women treated with 150 µg corifollitropin alfa (CFA)?Maternal and perinatal outcomes in programmed versus natural vitrified–warmed blastocyst transfer cycles
Do maternal and perinatal outcomes differ between natural and programmed frozen embryo transfer (FET) cycles?Cytogenetic testing of pregnancy loss tissue: a meta-analysis
Of all clinically recognized pregnancies, about 15% end in loss (Nybo Andersen et al., 2000; Rai and Regan, 2006). The great majority of pregnancy losses occur within the first trimester of pregnancy (Baird, 2009; Farr et al., 2007). Aneuploidy of the embryo is an important female age-related genetic cause of pregnancy loss and can be tested in pregnancy loss tissue (Hassold and Hunt, 2001; Rai and Regan, 2006). A proportion of couples (1–3%) not only suffer from one ‘sporadic’ pregnancy loss but from recurrent pregnancy loss, meaning two or more pregnancy losses (historically three or more losses) (Ford and Schust, 2009).Prospective randomized multicentre comparison on sibling oocytes comparing G-Series media system with antioxidants versus standard G-Series media system
Does the inclusion of three antioxidants (A3), acetyl-l-carnitine (ALC), N-acetyl-l-cysteine (NAC) and alpha-lipoic acid (ALA) improve human embryo development and pregnancy potential?Durations of intrauterine balloon therapy and adhesion reformation after hysteroscopic adhesiolysis: a randomized controlled trial
Does placing an intrauterine balloon for different durations (7, 14 or 28 days) affect the recurrence of intrauterine adhesions after hysteroscopic adhesiolysis?Context-based infertility care
Over the last few months we have reflected in these pages on a number of challenging issues that need to be addressed if clinical research in our field is to continue to impact on day-to-day infertility care (Macklon et al., 2019; Fauser and Macklon, 2019). As articulated by others (Horwitz et al 2017; Kent et al. 2018), we have argued that limiting clinical practice to only those interventions that have been shown to be ‘effective’ for a group of patients included in randomized controlled trials (RCTs) threatens to prevent rather than encourage the development of a clinically useful evidence-based medicine (EBM) for individual patients.Identification of research priorities in infertility and assisted reproduction: an international, multicentre study
What are the main research interests among patients of assisted reproductive technologies (ART)?‘There is only one thing that is truly important in an IVF laboratory: everything’ Cairo Consensus Guidelines on IVF Culture Conditions
This proceedings report presents the outcomes from an international expert meeting to establish consensus guidelines on IVF culture conditions. Topics reviewed and discussed were: embryo culture – basic principles and interactions; temperature in the IVF laboratory; humidity in culture; carbon dioxide control and medium pH; oxygen tension for embryo culture; workstations – design and engineering; incubators – maintaining the culture environment; micromanipulation – maintaining a steady physcochemical environment; handling practices; assessment practices; culture media – buffering and pH, general composition and protein supplementation, sequential or single-step media for human embryo culture; use and management – cold chain and storage; test equipment – calibration and certification; and laboratory equipment and real-time monitoring.Risk factors associated with pre-eclampsia in pregnancies conceived by ART
What are the factors associated with the increased incidence of pre-eclampsia in pregnancies conceived through IVF using autologous oocytes?Ovarian stimulation for oocyte vitrification does not modify disease-free survival and overall survival rates in patients with early breast cancer
Does ovarian stimulation for oocyte vitrification affect disease-free survival and overall survival rates in women with early breast cancer?Controversies in ART: can the IVF laboratory influence preimplantation embryo aneuploidy?
Published reports have indicated that rates of preimplantation embryo aneuploidy in a control donor population may vary between IVF centres. This suggests that location-specific conditions, in the clinic, IVF or genetics laboratory, may be influencing the chromosome dynamics or diagnosis. More recent reports suggest that rates of embryo mosaicism, representing mitotic errors, may vary between IVF centres. This would suggest perhaps a laboratory-controlled variable is influencing mitotic cell division during preimplantation embryo development.Use of progestins to inhibit spontaneous ovulation during ovarian stimulation: the beginning of a new era?
Advances in oocyte and embryo cryopreservation for assisted reproduction prompted new approaches to ovarian stimulation. Attention has been paid to progesterone and its derivatives to block the LH surge, as oocyte vitrification removes possible harmful effects of progestins on endometrial receptivity. This review summarizes the current status of progestin use to inhibit ovulation during ovarian stimulation compared with conventional ovarian stimulation. Progestin-primed ovarian stimulation is shown to effectively inhibit spontaneous ovulation, without affecting the number of retrieved oocytes and embryo quality.Childbirth close to natural menopause: does age at menopause matter?
Does a successful spontaneous pregnancy in the years close to natural menopause depend on age at menopause?Differential impacts of gonadotrophins, IVF and embryo culture on mouse blastocyst development
Conception via assisted reproductive technology (ART) increases the risk of type 2 diabetes and cardiovascular disease in adulthood. Underlying differences between ART-conceived and in-vivo-conceived embryos that contribute to this increased risk are, however, not known.Human growth hormone for poor responders: a randomized placebo-controlled trial provides no evidence for improved live birth rate
Does the addition of human growth hormone (HGH) to an IVF cycle improve the live birth rate in previously documented poor responders to FSH?Protective effect of oestrogen receptor α-PvuII transition against idiopathic male infertility: a case-control study and meta-analysis
Is there any genetic association between oestrogen receptor alpha [ERα]-PvuII polymorphism and idiopathic male infertility?Overnight ovarian tissue transportation for centralized cryobanking: a feasible option
Is overnight transportation of ovarian tissue before cryopreservation in a centralized cryobank from the FertiPROTEKT network feasible?Autologous endometrial cell co-culture improves human embryo development to high-quality blastocysts: a randomized controlled trial
Does autologous endometrial cell co-culture (AECC) improve the number of good-quality blastocysts obtained by IVF/intracytoplasmic sperm injection (ICSI), compared with conventional embryo culture medium in a broad group of patients referred to assisted reproductive technology (ART)?Morphokinetic parameters in chromosomal translocation carriers undergoing preimplantation genetic testing
Can embryo morphokinetic parameters help identify unbalanced embryos in translocation carriers?The impact of maternal lifestyle factors on periconception outcomes: a systematic review of observational studies
The main risk factors for important reproductive health issues such as subfertility and perinatal mortality largely originate in the periconception period. To evaluate associations between modifiable maternal lifestyle factors and periconception outcomes, a systematic search was conducted for relevant studies published from 1990 to February 2017 on Embase, Medline, Web of Science, Cochrane database, PubMed and Google Scholar. The initial search identified 6166 articles, of which 49 studies were eligible for inclusion.Imaging the ovary
Using mainly histological analyses of fixed ovarian tissues and ultrasound imaging of ovaries in vivo, earlier imaging studies have established the basic framework of ovarian folliculogenesis as well as luteal formation and regression. The ovary contains individual follicles as functional structures, together with corpora lutea, interstitial tissues, innermost medulla and the outmost layer of the surface epithelium. Most of the 800,000 primordial follicles found at birth in human females remain at the dormant stage.A search for molecular mechanisms underlying male idiopathic infertility
Infertility affects approximately 15% of the couples wanting to conceive. In 30 − 40% of the cases the aetiology of male infertility remains unknown and is called idiopathic male infertility. When assisted reproductive technologies are used to obtain pregnancy, an adequate (epi)genetic diagnosis of male infertility is of major importance to evaluate if a genetic abnormality will be transmitted to the offspring. In addition, there is need for better diagnostic seminal biomarkers to assess the success rates of these assisted reproductive technologies.The uterine fibroid/myoma tumour: analysis of the global research architecture using density-equalizing mapping
Uterine fibroids can severely impact a woman’s quality of life, result in significant morbidity and are a leading indication for hysterectomy. Many aspects of the disease remain largely obscure. Despite these knowledge gaps, no detailed maps of the global fibroid research architecture have yet been generated. This study used the NewQIS approach to assess worldwide research productivity, encompassing numerous aspects of the scientific output, quality and socioeconomic features. Regression analysis indicated an increase in fibroid research activity in the investigated time periods.Insights from clinical experience in treating IVF poor responders
‘Poor responders’ is a term used to describe a subpopulation of IVF patients who do not respond well to ovarian stimulation with gonadotrophins. While there is no standard definition of a poor responder, these patients tend to be of advanced maternal age (≥40 years), have a history of poor ovarian response with conventional stimulation protocols, and/or have low ovarian reserve. Despite the heterogeneity of this patient group, there are characteristics and needs common to many poor responders that can be addressed through a holistic approach.Perinatal outcomes after gestational surrogacy versus autologous IVF: analysis of national data
Anonymized data were obtained from the Human Fertilization and Embryology Authority to determine whether gestational surrogacy influences perinatal outcomes compared with pregnancies after autologous IVF. A total of 103,160 singleton live births, including 244 after gestational surrogacy, 87,571 after autologous fresh IVF and intractyoplasmic sperm injection (ICSI) and 15,345 after autologous frozen embryo transfers were analysed. Perinatal outcomes of pretern birth (PTB), low birth weight (LBW) and high birth weight (HBW) were compared.Chimeras intended for human gamete production: an ethical alternative?
Human eggs for basic, fertility and stem-cell research are in short supply. Many experiments that require their use cannot be carried out at present, and, therefore, the benefits that could emerge from these are either delayed or never materialise. This state of affairs is problematic for scientists and patients worldwide, and it is a matter that needs our attention. Recent advances in chimera research have opened the possibility of creating human/non-human animal chimeras intended for human gamete production (chimeras-IHGP).Timing therapeutic donor inseminations in natural cycles: human chorionic gonadotrophin administration versus urinary LH monitoring
This cohort study assessed whether timing therapeutic donor sperm inseminations (TDI) in natural cycles (NC) using ultrasound monitoring and ovulation trigger with human chorionic gonadotrophin (US/HCG) improves cumulative live birth rates (LBR) compared with detection of LH surge with urinary kits (u-LH). It included 232 normo-ovulatory women aged ≤40 years, undergoing 538 TDI in NC between 2011 and 2014. In the u-LH group (113 women, 267 cycles), TDI was performed the day following a positive test.Bio-equivalent doses of recombinant HCG and recombinant LH during ovarian stimulation result in similar oestradiol output: a randomized controlled study
In nature, HCG is secreted by the implanting embryo from peri-implantation and onwards. In contrast, LH is mandatory for steroidogenesis and follicular development during the follicular phase, working in synergy with FSH. Moreover, LH is mandatory for the function of the corpus luteum. Although LH and HCG bind to the same receptor, significant molecular, structural and functional differences exist, inducing differences in bioactivity. This randomized controlled study compared the effect of recombinant FSH stimulation combined with daily either micro-dose recombinant HCG or recombinant LH supplementation in a 1:1 bioactivity ratio from day 1 of stimulation in a long gonadotrophin releasing hormone agonist down regulation protocol.Chromosomal polymorphisms are associated with female infertility and adverse reproductive outcomes after infertility treatment: a 7-year retrospective study
Data from 19,950 women were retrospectively analysed to determine the effect of chromosomal polymorphisms on female infertility and pregnancy outcome; fertile women were used as controls. Frequency of chromosomal polymorphisms and adverse pregnancy outcomes were compared between groups. A significantly higher incidence of chromosomal polymorphisms was found in total infertile patients, and patients with tubal infertility, ovulatory dysfunction, cervical and uterine abnormalities, and unexplained infertility compared with controls (5.53% [P < 0.001], 4.86% [P = 0.012] 5.40% [P < 0.001], 5.75% [P < 0.001] and 8.51% [P < 0.001], versus 3.74%, respectively).Live birth derived from oocyte spindle transfer to prevent mitochondrial disease
Mutations in mitochondrial DNA (mtDNA) are maternally inherited and can cause fatal or debilitating mitochondrial disorders. The severity of clinical symptoms is often associated with the level of mtDNA mutation load or degree of heteroplasmy. Current clinical options to prevent transmission of mtDNA mutations to offspring are limited. Experimental spindle transfer in metaphase II oocytes, also called mitochondrial replacement therapy, is a novel technology for preventing mtDNA transmission from oocytes to pre-implantation embryos.Ovarian tissue cryopreservation in female-to-male transgender people: insights into ovarian histology and physiology after prolonged androgen treatment
Female-to-male transgender people (trans men), are faced with the risk of losing their reproductive potential owing to gender affirming hormone treatment and genital reconstructive surgery. Transgender people also tend to start sex reassignment treatment at a young age, when reproductive wishes are not yet clearly defined nor fulfilled (De Sutter, 2001). About one-half of trans men, however, express the desire to have children (Wierckx et al., 2012). It is, therefore, recommended by the most recent Standards of Care of the World Professional Association for Transgender Health to clearly discuss fertility and fertility preservation before any treatment (Coleman et al., 2012).Anti-Müllerian hormone kinetics in pregnancy and post-partum: a systematic review
The aim of this systematic review is to critically appraise the available evidence regarding the kinetics of anti-Müllerian hormone (AMH) during pregnancy and post-partum. A systematic literature search was conducted in MEDLINE, Embase, CENTRAL, Scopus and Web of Science on 14 December 2015, aiming to identify studies providing data on the serum concentration of AMH in women at various stages of gestation and post-partum. There was a total of 1719 participants across eight studies. Seven out of the eight studies reported a decline in serum AMH concentration with advancing gestational age.‘Model’ versus ‘everyday’ patients: can randomized controlled trial data really be applied to the clinic?
New drug approval requires a new drug to undergo rigorous clinical trials to determine its efficacy and safety. A drug is approved only for the population on which it was tested, i.e. those who meet the inclusion criteria of the trial. The aim of this study was to determine what percentage of ‘real life’ patients in our clinic meet the inclusion and exclusion criteria used in large-scale clinical trials required for drug registration in the field of assisted reproduction. All 265 consecutive patients with pertinent data treated in a tertiary centre IVF Unit during 2015 were surveyed.Embryos with morphokinetic abnormalities may develop into euploid blastocysts
Irregular cleavage divisions are expected to produce chromosomally deviant embryos. We investigated whether embryos from irregular cleavages could develop into euploid blastocysts, and, if so, whether any evidence existed of a self-correction mechanism of the embryo. We also investigated the role of different dynamic aspects of morula compaction in this process. A total of 791 embryos from 141 patients undergoing pre-implantation genetic screening were retrospectively analysed using a time-lapse imaging system, and multiple cell divisions were evaluated.Increased miscarriage of euploid pregnancies in obese women undergoing cryopreserved embryo transfer
Obesity is known to be associated with an increased risk of miscarriage after natural and assisted conception. Although most sporadic miscarriages are caused by genetic abnormalities, it is presently uncertain if genetics is also the underlying mechanism leading to increased pregnancy loss seen in obese women. Karyotyping of the products of conception suggests a reduced rate of fetal aneuploidy in miscarriages from obese compared with lean individuals. Karyotype analysis, however, is prone to false negative results because of inadvertent culture of maternal rather than fetal tissue.Subfertility factors rather than assisted conception factors affect cognitive and behavioural development of 4-year-old singletons
Research on cognitive and behavioural development of children born after assisted conception is inconsistent. This prospective study aimed to explore underlying causal relationships between ovarian stimulation, in-vitro procedures, subfertility components and child cognition and behaviour. Participants were singletons born to subfertile couples after ovarian stimulation IVF (n = 63), modified natural cycle IVF (n = 53), natural conception (n = 79) and singletons born to fertile couples (reference group) (n = 98).Disclosure of sperm donation: a comparison between solo mother and two-parent families with identifiable donors
Disclosure of donor conception to children was compared between solo mother and two-parent families with children aged 4–8 years conceived since the removal of donor anonymity in the UK. Semi-structured interviews were conducted with 31 heterosexual solo mothers and 47 heterosexual mothers with partners to investigate their decisions and experiences about identifiable donation and disclosure to their children. No significant difference was found in the proportion of mothers in each family type who had told their children about their donor conception (solo mothers 54.8%; partnered mothers 36.2%).Pregnancy derived from human zygote pronuclear transfer in a patient who had arrested embryos after IVF
Nuclear transfer of an oocyte into the cytoplasm of another enucleated oocyte has shown that embryogenesis and implantation are influenced by cytoplasmic factors. We report a case of a 30-year-old nulligravida woman who had two failed IVF cycles characterized by all her embryos arresting at the two-cell stage and ultimately had pronuclear transfer using donor oocytes. After her third IVF cycle, eight out of 12 patient oocytes and 12 out of 15 donor oocytes were fertilized. The patient's pronuclei were transferred subzonally into an enucleated donor cytoplasm resulting in seven reconstructed zygotes.Survival and growth of human preantral follicles after cryopreservation of ovarian tissue, follicle isolation and short-term xenografting
In women, chemotherapy and radiotherapy can be harmful to the ovaries, causing loss of endocrine and reproductive functions. When gonadotoxic treatment cannot be delayed, ovarian tissue cryobanking is the only way of preserving fertility. This technique, however, is not advisable for patients with certain types of cancer, because of the risk of reintroducing malignant cells present in the cryopreserved tissue. Our objective is therefore to develop a transplantable artificial ovary. To this end, cryopreserved human preantral follicles were isolated and embedded in fibrin formulations prepared with 50 mg/ml fibrinogen and 10 IU/ml thrombin supplemented or not with 3% hyaluronic acid, and respectively xenografted to specially created right and left peritoneal pockets in eight nude mice.Sperm cryopreservation and reproductive outcome in male cancer patients: a systematic review
This systematic review of the literature reports on the use and effectiveness of sperm banking programmes for cancer patients. Thirty studies with 11798 patients were included. The aggregated rate of use of cryopreserved semen was 8% (95% CI 8 to 9%). A statistically significant correlation emerged between the mean and median duration of follow-up and the rate of use (R2 = 0.46; P = 0.03). The rate of patients discarding their frozen sample was reported in 11 studies. The aggregated rate was 16% (95% CI 15 to 17%).Endometrial transcriptome analysis indicates superiority of natural over artificial cycles in recurrent implantation failure patients undergoing frozen embryo transfer
Little consensus has been reached on the best protocol for endometrial preparation for frozen embryo transfer (FET). It is not known how, and to what extent, hormone supplementation in artificial cycles influences endometrial preparation for embryo implantation at a molecular level, especially in patients who have experienced recurrent implantation failure. Transcriptome analysis of 15 endometrial biopsy samples at the time of embryo implantation was used to compare two different endometrial preparation protocols, natural versus artificial cycles, for FET in women who have experienced recurrent implantation failure compared with fertile women.GnRH agonist trigger for the induction of oocyte maturation in GnRH antagonist IVF cycles: a SWOT analysis
Gonadotrophin releasing hormone agonist (GnRHa) trigger is effective in the induction of oocyte maturation and prevention of ovarian hyperstimulation syndrome during IVF treatment. This trigger concept, however, results in early corpora lutea demise and consequently luteal phase dysfunction and impaired endometrial receptivity. The aim of this strenghths, weaknesses, opportunities and threats analysis was to summarize the progress made over the past 15 years to optimize ongoing pregnancy rates after GnRHa trigger.Factors associated with willingness to donate embryos for research among couples undergoing IVF
Most couples enrolled in IVF and intracytoplasmic sperm injection (ICSI) cycles need to make decisions about embryo disposition (Provoost et al., 2010; Wånggren et al., 2013). It has been consistently shown that this is a complex decision-making process, involving different sequential stages that can change over time (de Lacey, 2005; Provoost et al., 2009, 2012a). Patients undergoing IVF usually reveal multifaceted views about embryo status (Haimes and Taylor, 2009; Provoost et al., 2009), disagreements between partners (Provoost et al., 2012b) and emotional distress (de Lacey, 2005; Fuscaldo et al., 2007).Women's intentions to use fertility preservation to prevent age-related fertility decline
The optimal age to cryopreserve oocytes for later use is before 36 years. Current users are on average 38 years old. In this cross-sectional study an online survey was constructed about the factors associated with the intentions of childless women aged 28–35 years to use fertility preservation (FP). Questions were derived from the Theory of Planned Behaviour (attitudes and subjective norms regarding FP and perceived behaviour control to do FP) and the Health Belief Model (perceived susceptibility of infertility, perceived severity of childlessness, barriers and benefits of FP and cue to use FP).Increasing fertility knowledge and awareness by tailored education: a randomized controlled trial
Women of reproductive age have insufficient fertility knowledge and awareness. Reproductive lifespan and assisted reproduction are the primary areas in which awareness is lacking. Relatively simple interventions can be used to increase knowledge among university students; however, no intervention has been tested to date in a population with more varied education levels. The aim of this study was to evaluate which intervention most improved fertility knowledge in women attending a fertility centre for oocyte donation.The endocrine function of human placenta: an overview
During pregnancy, several tightly coordinated and regulated processes take place to enable proper fetal development and gestational success. The formation and development of the placenta is one of these critical pregnancy events. This organ plays essential roles during gestation, including fetal nourishment, support and protection, gas exchange and production of several hormones and other mediators. Placental hormones are mainly secreted by the syncytiotrophoblast, in a highly and tightly regulated way.The effect of protein supplement concentration in embryo transfer medium on clinical outcome of IVF/ICSI cycles: a prospective, randomized clinical trial
The aim of this prospective, randomized clinical trial (RCT) was to evaluate whether the supplemental protein concentration in embryo transfer (ET) medium affects the clinical outcomes in IVF–ET. A total of 750 patients undergoing IVF–ET who met the inclusion criteria were randomly divided into three groups, according to the concentration of synthetic serum substitute (SSS) in ET medium as follows: 10% (Group A), 20% (Group B) and 50% (Group C). The patient characteristics and embryology data were all similar among the groups.Association between leukaemia inhibitory factor gene polymorphism and pregnancy outcomes after assisted reproduction techniques
Certain gene polymorphisms are associated with implantation failure and pregnancy loss. Studies of leukaemia inhibitory factor (LIF) gene polymorphisms are scarce. The LIF single nucleotide polymorphism (SNP) thymine (T)/guanine (G) (rs929271) was studied in women to determine whether an association existed with pregnancy outcomes after intracytoplasmic sperm injection (ICSI); 411 women who underwent ICSI were recruited. DNA was extracted from the peripheral blood, and the LIF gene SNP T/G (rs929271) was genotyped using real-time polymerase chain reaction.Baby factories taint surrogacy in Nigeria
The practice of reproductive medicine in Nigeria is facing new challenges with the proliferation of ‘baby factories’. Baby factories are buildings, hospitals or orphanages that have been converted into places for young girls and women to give birth to children for sale on the black market, often to infertile couples, or into trafficking rings. This practice illegally provides outcomes (children) similar to surrogacy. While surrogacy has not been well accepted in this environment, the proliferation of baby factories further threatens its acceptance.Polymorphism of CAG and GGN repeats of androgen receptor gene in women with polycystic ovary syndrome
One characteristic of polycystic ovary syndrome (PCOS) is hyperandrogenism, which may be related to the activity of androgen receptor (AR). This study was designed to investigate the polymorphism of CAG and GGN repeats in the AR gene in women with PCOS. The frequency distributions of CAG and GGN repeat alleles, as well as their X-inactivation patterns, were compared between 76 age-matched normal women (control group) and 80 women with PCOS (PCOS group). The expression of AR mRNA in the ovarian tissues of seven patients with PCOS and five normal women was also tested using real-time quantitative PCR.A pilot study to evaluate a device for the intravaginal culture of embryos
The aim of this comparative randomized embryology trial was to determine if an intravaginal culture device (IVC) can provide acceptable embryo development compared with conventional IVF. Ten women between the ages of 27 and 37 years with an indication for IVF treatment were included in this study. After ovarian stimulation, oocytes were randomized to fertilization in the IVC device or using conventional IVF. Fertilization rates were higher in the IVF group compared with the IVC device (68.7% ± 36 % versus 40.7% ± 27%), respectively, whereas cleavage rates were similar (93% ± 1.5% versus 97% ± 6%) for both groups.What's in a name? Variations in terminology of third-party reproduction
The terminology used to discuss third-party reproduction, as with other new biomedical processes, can ease or impede communication and even influence behaviour. In an effort to sensitize analysts and stakeholders to variations in terminology and to facilitate communication on issues arising from international surrogacy arrangements, this paper examines variations in terms used. We introduce some of the issues previously raised by scholars concerned with analysis of discourse related to third-party reproduction.Validation of next-generation sequencing for comprehensive chromosome screening of embryos
Massively parallel genome sequencing, also known as next-generation sequencing (NGS), is the latest approach for preimplantation genetic diagnosis. The purpose of this study was to determine whether NGS can accurately detect aneuploidy in human embryos. Low coverage genome sequencing was applied to trophectoderm biopsies of embryos at the blastocyst stage of development. Sensitivity and specificity of NGS was determined by comparison of results with a previously validated platform, array-comparative genomic hybridization (aCGH).Intended parents' motivations and information and support needs when seeking extraterritorial compensated surrogacy
Cross-border reproductive care (CBRC) is becoming increasingly common. Little is known about the motivations and information and support needs of people who cross borders to access surrogacy. This study aimed to explore: how those considering or undertaking extraterritorial surrogacy reach their decision; what other avenues they have considered and tried to have children; their sources of information and support; and perceptions of how others view their decision. Members of two Australian parenting support forums completed an anonymous online survey.System for evaluation of oxidative stress on in-vitro-produced bovine embryos
This study proposed a quantitative evaluation of oxidative status (OS) in bovine embryos. Sixteen-cell stage embryos, cultured under 5% O2, were treated with oxidative stress inducer menadione (0, 1, 2.5 and 5 µmol/l) for 24 h. Blastocyst rate (BLR) was recorded and expanded blastocysts were stained with CellROX®Green (CRG; OS evaluation) and evaluated under epifluorescence microscopy (ratio of pixel/blastomere). A significant effect of menadione was observed for BLR (P = 0.0039), number of blastomeres/embryo (P < 0.0001) and OS (P < 0.001).Live births following Karyomapping of human blastocysts: experience from clinical application of the method
The clinical application of a new, widely applicable method known as Karyomapping to carry out a total of 55 clinical cases of preimplantation genetic diagnosis (PGD) for single gene disorders is reported. Conventional polymerase chain reaction (PCR) testing was carried out in parallel to the new method for all cases. Clinical application of Karyomapping in this study resulted in three live births and nine clinical pregnancies out of 20 cases with a transfer. All in all, results presented in this study indicate that Karyomapping is a highly efficient, accurate and robust method for PGD of single gene disorders.Genetic variants associated with female reproductive ageing – potential markers for assessing ovarian function and ovarian stimulation outcome
This study searched for genetic markers of ovarian function, ovarian stimulation and IVF treatment outcome among genetic variants related to female reproductive ageing. It included 471 treatment cycles from 306 women undergoing IVF treatment. Genotypes for 36 single nucleotide polymorphisms (SNPs) were evaluated for their association with early follicular phase parameters together with ovarian stimulation and IVF outcome parameters. Results show that genetic variation related to menopause timing also affects ovarian function, as several selected genetic markers were associated with studied traits.Physical activity, fatness, educational level and snuff consumption as determinants of semen quality: findings of the ActiART study
In this study, the association between physical activity and other potential determinants, objectively measured by accelerometry, was examined. Sixty-two men attending an infertility clinic participated in the study. Obese men (body mass index ≥ 30) and those with a waist circumference 102 cm or more had lower semen volume than the other men (P < 0.05). Higher values in sperm parameters were observed in participants who completed university studies and those who did not consume snuff, compared with the other participants (P < 0.05).Fresh and cryopreserved ovary transplantation and resting follicle recruitment
Ovary cryopreservation and transplantation has garnered increasing interest as a possible method to preserve fertility for cancer patients and to study ovarian resting follicle recruitment. Eleven consecutive women underwent fresh donor ovary transplantation, and 11 underwent cryopreserved ovary auto-transplantation in the same centre, with the same surgeon. Of the 11 fresh transplant recipients, who were all young but menopausal, nine women had normal ovarian cortex transplanted from an identical twin sister, and two had a fresh allograft from a non-identical sister.Cytoplasmic, rather than nuclear-DNA, insufficiencies as the major cause of poor competence of vitrified oocytes
An oocyte is a unique body cell that is developmentally committed to support fertilization and early embryonic development (Hosseini et al., 2012). This capacity strongly depends on the cellular and molecular aspects of nucleo-cytoplasmic interactions, which facilitate early mitotic divisions of the embryo until broad embryonic genome activation (Sirard, 2012). During vitrification, this highly organized structure often incurs serious damage which inevitably affects its capacity to respond to subsequent treatment (Smith et al., 2011).Non-synchronized endometrium and its correction in non-ovulatory cryopreserved embryo transfer cycles
The aim of this case series study was to investigate the effect of adjusting the length of progesterone exposure on clinical pregnancy rates in cryopreserved embryo transfer cycles of patients with out-of-phase classic endometrial dating. Eighty infertile women with previous implantation failure and good-quality embryos underwent endometrial biopsy before cryopreserved embryo transfer and were included in this study. The main outcome measures were clinical pregnancy rate and histologic endometrial dating.Impact of blastocyst biopsy and comprehensive chromosome screening technology on preimplantation genetic screening: a systematic review of randomized controlled trials
Embryonic aneuploidy is highly prevalent in IVF cycles and contributes to decreased implantation rates, IVF cycle failure and early pregnancy loss. Preimplantation genetic screening (PGS) selects the most competent (euploid) embryos for transfer, and has been proposed to improve IVF outcomes. Use of PGS with fluorescence-in-situ hybridization technology after day 3 embryo biopsy (PGS-v1) significantly lowers live birth rates and is not recommended for use. Comprehensive chromosome screening technology, which assesses the whole chromosome complement, can be achieved using different genetic platforms.Reporting of embryo transfer methods in IVF research: a cross-sectional study
If we accept that reproducibility is one of the principles of the scientific method (Siegel, 2011), then reporting the methods of research is equally important as disseminating its results. A good description of a study's methodology allows others to replicate the experiment accurately and verify previous findings. Current research, however, shows that scientific reporting can often be inadequate, even in the case of high-quality studies such as randomized controlled trials (Péron et al., 2012; Turner et al., 2012; Wang et al., 2011).No evidence of association between blastocyst aneuploidy and morphokinetic assessment in a selected population of poor-prognosis patients: a longitudinal cohort study
Recent studies involving a limited number of patients have indicated a correlation between aneuploidy and various morphokinetic parameters during preimplantation development. The results among different groups, however, have been inconsistent in identifying the parameters that are able to predict chromosomal abnormalities. The aim of this study was to investigate whether aneuploidy of human blastocysts was detectable by specific morphokinetic parameters in patients at increased risk of aneuploidy because of advanced maternal age, history of unsuccessful IVF treatments, or both.Effects of in-vitro or in-vivo matured ooplasm and spindle-chromosome complex on the development of spindle-transferred oocytes
To study the effects of in-vitro matured ooplasm and spindle-chromosome complex (SCC) on the development of spindle-transferred oocytes, reciprocal spindle transfer was conducted between in-vivo and in-vitro matured oocytes. The reconstructed oocytes were divided into four groups according to their different ooplasm sources and SCC, artificially activated and cultured to the blastocyst stage. Oocyte survival, activation and embryo development after spindle transfer manipulation were compared between groups.Double stimulations during the follicular and luteal phases of poor responders in IVF/ICSI programmes (Shanghai protocol)
Previous studies have shown that existing antral follicles in the luteal phase enable ovarian stimulation. In a pilot study, the efficacy of double stimulations during the follicular and luteal phases in women with poor ovarian response was explored (defined according to the Bologna criteria). Thirty-eight women began with mild ovarian stimulation. After the first oocyte retrieval, human menopausal gonadotrophin and letrozole were administrated to stimulate follicle development, and oocyte retrieval was carried out a second time when dominant follicles had matured.
