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Department of Obstetrics and Gynecology, New York University, Langone Medical Center, New York, New York, USA
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Lay summary
The placenta plays an essential role at the beginning of life, nourishing and supporting the fetus, but its life span is limited. In late pregnancy, the placenta develops signs of aging, including inflammation and impaired function, which may complicate pregnancy. Placentas also show another sign of aging – cells with extra or missing chromosomes. Chromosomally abnormal cells could gather in the placenta if they get stranded there and/or if the cells do not separate normally. Chromosome separation goes wrong in aging cells when the DNA sequences, which protect the ends of the chromosomes, erode. When chromosomes lose their protective caps, they fuse which leads to abnormal numbers of chromosomes. In this pilot study, for the first time, we found fusions between the caps in a human placenta when it reaches full term. More studies are needed to decide whether this has an influence on how the placenta works and outcomes of pregnancy.
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Yellowish myotis present a seasonal reproduction, influenced by rainfall distribution, in which the testis mass, germ cell composition, and brown adipose tissue (B.A.T.) mass change along the reproductive stages. In the present study, tissue xenografts were performed in immunodeficient mice to investigate spermatogenesis development in a stable endocrine milieu and the possible androgenic role of B.A.T. In this study, 41 adult male bats were captured in the Santuário do Caraça, Minas Gerais, Brazil. The gonads and B.A.T. were collected, weighed, and grafted under the mice's back skin. Mice biometric and hormonal data were evaluated after grafting, and the testis grafts and mice gonads were fixed for histological and immunohistochemical analyses. As a result, testis grafts from adult bats presented a continuous germ cell development in all reproductive stages, showing round spermatids in all testis tissues. Furthermore, testis fragments in the Rest stage presented elongating spermatids as the most advanced germ cell type in the seminiferous epithelium after 7 months of grafting. These data indicated that yellowish myotis spermatogenesis could be continued (presenting a constant spermatogonial differentiation) in a stable endocrine milieu, as found in mice. In addition, the best spermatogenic development was achieved when testis fragments were transplanted at their lowest activity (Rest stage). Regarding the B.A.T. grafts, the adipose tissue consumption by mice increased seminal vesicle mass and testosterone serum levels. This data proves that B.A.T. is related to testosterone synthesis, which may be critical in stimulating the differentiation of spermatogonia in yellowish myotis.
Lay summary
Bats are essential seed dispersers, pollinators, and agricultural pest regulators. Despite their ecological importance, bats face different threats due to environmental destruction and usually have few offspring per year. This study aimed to understand better how bats reproduce, but studying them in captivity is complicated and may not replicate what happens in the natural environment. To overcome this obstacle, we transplanted tissues from bats into mice which allowed in-depth research in lab conditions into bat reproduction. We looked at the tissues of adult bats after they had been transplanted into mice, and this allowed us to see which types of tissue played a critical role in reproduction.
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Complete Fertility Centre Southampton, Princess Anne Hospital, Division of Women and Newborn, Southampton, UK
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Endometrial glands are essential for fertility, consisting of ciliated and secretory cells that facilitate a suitable uterine environment for embryo implantation. This study sought to determine whether an endometrial gland-specific transcriptome and splicing profile are altered in women with recurrent pregnancy loss. Our data provide a comprehensive catalogue of cilia and progestagen-associated endometrial protein (PAEP) gene isoforms and relative exon usage in endometrial glands. We report a previously unannotated endometrial gland cilia transcript GALNT11 and its susceptibility to exon skipping. Key endometrial receptivity gene transcripts are also reported to change in endometrial glands of women with recurrent pregnancy loss. The endometrial gland cilia and PAEP targets identified in this study could be used to identify a perturbed endometrium, isolate causes of recurrent pregnancy loss and develop targeted therapies in personalised medicine.
Lay summary
Successful embryo implantation is a trade-off between the lining of the womb which receives an implanting embryo, termed the endometrium, and a good quality embryo. For days 21–24 of the menstrual cycle, the endometrium undergoes changes into a receptive state in which it can receive an implanting embryo. Inappropriate endometrial receptivity is thought to underlie recurrent pregnancy loss. Improving pregnancy success in women with recurrent pregnancy loss requires an increased understanding of the endometrium at the molecular level. Genes contain the instructions for the cell and which genes are turned on or off determine how well it can do its role. We sought to determine a gene expression pattern of human endometrial glands in women with recurrent pregnancy loss (n = 5) vs a control group (n = 5). We identify target genes altered in women with recurrent pregnancy loss. Endometrial gland markers could be used to identify inappropriate endometrial receptivity.
Fertility Centre, Lanka Hospitals Corporation Plc, Colombo, Sri Lanka
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NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, UK
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The use of intracytoplasmic sperm injection (ICSI) has recently increased worldwide. The live birth rate per ICSI cycle is low, and over half of infertile couples remain childless. Chromosomal polymorphisms are up to five times more common in couples with infertility compared to the general population. We aimed to investigate the association between chromosomal polymorphisms and reproductive outcomes in couples undergoing ICSI treatment. We analysed 942 ICSI fresh and frozen embryo transfer cycles in 697 women who underwent karyotyping analysis using Giemsa-Trypsin-Leishman banding prior to assisted conception at the Fertility Centre of Lanka Hospitals, Sri Lanka, between 2016 and 2018. The primary outcomes were pregnancy, miscarriage, and live birth rates. We compared outcomes according to the presence or absence of chromosomal polymorphism in females, males and couples. There were 294 pregnancies (31.2%) recorded in the study; 130 suffered a miscarriage (13.8%), 13 were ectopic pregnancies (1.3%) and 151 resulted in a live birth (16.0%). The evidence from univariable and multivariable analyses (adjusted for age, BMI, ovarian reserve and treatment type) did not confidently identify a difference in pregnancy, miscarriage or live birth rates between couples with no chromosomal polymorphisms compared to couples where the female, male or both partners were carriers of a chromosomal polymorphism. Further, we did not identify a clear association between the presence of chromosomal polymorphisms and reproductive outcomes compared to participants without chromosomal polymorphisms. Wide CIs precluded the identification of clinically meaningful associations.
Lay summary
Infertility affects approximately one in eight couples worldwide. The use of intracytoplasmic sperm injection (ICSI), where the sperm is directly injected into an egg using a micromanipulator outside the body, has become particularly popular in recent years. However, the success rate remains low. In human cells, the genetic material is arranged in structures called chromosomes. Chromosomal polymorphism is a normal variation where the genetic material is arranged differently to the average individual and is more common in infertile couples compared to the general population. We analysed data from 942 ICSI cycles in 697 couples who underwent karyotyping analysis to assess the changes in chromosomes between 2016 and 2018. The pregnancy rate was 31.2%, with 16.0% of participants experiencing a live birth, while 13.8% of pregnancies resulted in a miscarriage and 1.3% were outside the womb cavity (ectopic). The evidence did not identify a clear association between the chromosomal polymorphism and the outcome of treatment.
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Graphical abstract
Abstract
This study was carried out to investigate whether repeated controlled ovarian hyperstimulation (COH) affects ovarian reserve. For this reason, we aimed to show possible changes in the expression of PTEN and FOXO3, which are involved in preserving the over-reserve, after applying the COH protocol methods. For this purpose, 18 young Wistar albino female rats (8 weeks old) were randomly assigned as group 1 (control), group 2, and group 3 as 6 subjects in each group. Experimental groups were treated with 10 IU/0.1 mL pregnant mare’s serum gonadotropin and a COH protocol consisting of 10 IU/0.1 mL human chorionic gonadotropin injection after 48 h. This procedure was applied three and five times to group 2 and group 3, respectively. For the control groups, the same procedures were performed with 0.1 mL of 0.9% sodium chloride solution. At the end of the experiment, the ovarium tissues were placed in a 10% neutral formaldehyde solution for light microscopic examinations. In histological sections stained with hematoxylin and eosin, the number of ovarian follicles was determined using the physical dissector method. However, the expression of PTEN, FOXO3, and LH-R molecules was evaluated by immunohistochemical methods. As a result of our study, it was concluded that COH administration reduces the expression levels of PTEN and FOXO3 proteins and LH-R, which are among the essential components of the PIK3 intracellular signaling pathway and also increased the levels of hormones such as follicle-stimulating hormone, estradiol, and luteinizing hormone, which are over-reserve markers, and causes adverse effects on the histological structure, oocyte morphology, and number of ovaries.
Lay summary
Today, approximately 10–15% of couples experience fertility problems. However, assisted reproductive techniques help people with fertility problems to get pregnant. The main purpose of these techniques is to put the sperm and egg together outside the woman’s body where the eggs are fertilized and then to return the fertilized eggs (embryos) to the womb. During a woman’s menstrual cycle, several hormones influence the growth of the eggs. This process can be mimicked by using various medications. Medication is given to increase the number of eggs that develop. However, this method is not the same as normal ovulation. Therefore, in our study, we wanted to examine the effect that developing multiple follicles has on the number and quality of eggs remaining for the future.
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In vitro
culturing of endometrial cells obtained from the uterine mucosa or ectopic sites is used to study molecular and cellular signalling relevant to physiologic and pathologic reproductive conditions. However, the lack of consensus on standard operating procedures for deriving, characterising and maintaining primary cells in two- or three-dimensional cultures from eutopic or ectopic endometrium may be hindering progress in this area of research. Guidance for unbiased in vitro research methodologies in the field of reproductive science remains essential to increase confidence in the reliability of in vitro models. We present herein the protocol for a Delphi process to develop a consensus on in vitro methodologies using endometrial cells (ENDOCELL-Seud Project). A steering committee composed of leading scientists will select critical methodologies, topics and items that need to be harmonised and that will be included in a survey. An enlarged panel of experts (ENDOCELL-Seud Working Group) will be invited to participate in the survey and provide their ratings to the items to be harmonised. According to Delphi, an iterative investigation method will be adopted. Recommended measures will be finalised by the steering committee. The study received full ethical approval from the Ethical Committee of the Maastricht University (ref. FHML-REC/2021/103). The study findings will be available in both peer-reviewed articles and will also be disseminated to appropriate audiences at relevant conferences.
Lay summary
Patient-derived cells cultured in the lab are simple and cost-effective methods used to study biological and dysfunctional or disease processes. These tools are frequently used in the field of reproductive medicine. However, the lack of clear recommendations and standardised methodology to guide the laboratory work of researchers can produce results that are not always reproducible and sometimes are incorrect. To remedy this situation, we define here a method to ascertain if researchers who routinely culture cells in the lab agree or disagree on the optimal laboratory techniques. This method will be used to make recommendations for future researchers working in the field of reproductive biology to reproducibly culture endometrial cells in the laboratory.
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Kirinyaga University, Kerugoya, Kenya
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Endometriosis has long been wrongly perceived to be rare among women of African descent. The misconception about the prevalence of endometriosis among African women has significantly contributed to long diagnostic delays, limited access to diagnosis and care, and a scarcity of research on the condition among African women. In this commentary, we highlight the prevalence of endometriosis among African women, the state of endometriosis care in Africa, and the gaps in knowledge that need to be addressed. Based on the available data, the prevalence of endometriosis in Africa is likely higher than previously thought, with varying subtypes. There is a long diagnostic delay of endometriosis among African women. Additionally, endometriosis care in Africa from the general population and health practitioners is poor; this can be attributed to the high diagnostic cost, scarcity of trained specialists, as well as patients’ inability to express their symptoms due to societal taboos surrounding menstrual health. Public sensitization on endometriosis may help improve endometriosis diagnosis and care in Africa.
Lay summary
Endometriosis is a condition in which tissue like the uterine lining is found outside the uterus, causing women to experience pain especially before, during, or after menstruation. Although endometriosis affects an estimated 176 million women worldwide, it has been wrongly reported that endometriosis is a rare condition among African women, mainly due to lack of awareness among healthcare providers and historical bias. In the current commentary, we discuss the prevalence of endometriosis, the diagnostic delays, and the care of endometriosis among black African women living in the African continent. Much of the literature has demonstrated (falsely) that endometriosis is rare in Black women compared to White ethnicity. African women experience a long diagnostic delay and do not receive appropriate care. Public awareness of endometriosis may help improve diagnosis delay and endometriosis care in Africa.
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Lay summary
The need to develop new treatments to prevent unprompted premature delivery before 37 weeks of pregnancy remains pressing and unmet. Bacteria (Lactobacillus species) that promote vaginal health produce biochemical compounds that prevent the growth of microbes such as Gardnerella vaginalis. Overgrowth of G. vaginalis can cause vaginal infection with smelly discharge and increase a woman’s risk of sexually transmitted infections and premature delivery. In this study, we examined how normal health-promoting (L. crispatus) and potentially harmful (G. vaginalis) vaginal bacteria interact in a laboratory setting. This was in order to observe natural and effective agent(s) from L. crispatus that can hinder the growth of G. vaginalis and accompanying immune response. We observed that L. crispatus clears G. vaginalis by itself and with several biochemical compounds that it produces. Such biochemical compounds can be developed into treatment for vaginal infections and premature delivery due to infection and inappropriate immune response.
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To gain more knowledge about the influence of hormone regulation on follicle development, ovarian ultrasounds were performed, and urinary hormone profiles were determined in ovulating and non-ovulating female bottlenose dolphins (n = 15) following estrus synchronization with altrenogest. Ovarian ultrasounds were conducted daily, post-synchronization to describe follicular recruitment in relation to the endocrine profile. Follicle sizes were grouped into very small (VSM), small (SM), medium (MD) and large (LG). In ovulating females, two follicular waves were identified, and follicular deviation toward establishing a dominant follicle only occurred during the second wave. For non-ovulating females, only the first wave was observed. For all urinary hormones, the non-ovulating group presented significantly lower concentrations of follicle-stimulating hormone (uFSH), luteinizing hormone (uLH), estrone conjugates (uE1-C) and estriol (uE3) but similar progestagen and cortisol concentrations compared to the ovulating group. Concentrations of uE1-C and uE3 and the numbers of MD and LG follicles significantly (P < 0.05) increased, while uFSH concentrations significantly (P < 0.05) decreased as ovulation approached. Urinary LH significantly increased concurrently with increasing numbers of LG follicles and decreasing numbers of SM follicles. The characterization of follicular development and its relationship with hormone assessment complements our understanding of follicular recruitment post-synchronization in bottlenose dolphins and provides new information concerning differences between ovulating and non-ovulating females in response to an estrous synchronization protocol.
Lay summary
Many species of fresh and saltwater dolphins and porpoises are facing increasing pressure for food and habitats due to human activities. One of the primary aspects that can be affected by such activities is reproduction. The bottlenose dolphin has been successfully bred in zoos and aquariums for at least 70 years, and they can be trained for several voluntary behaviors that enable medical examinations. Therefore, they represent a unique resource for research and understanding of normal dolphin reproduction. In this research, voluntary ultrasound exams and urine samples from 15 female dolphins were used to describe changes in their ovaries. The resulting descriptions and comparisons provide insight into the unique ovarian physiology of bottlenose dolphins and into the differences between animals after treatment. This information adds to the body of knowledge which one day may be used for developing advanced reproductive techniques to help preserve endangered species of dolphins.
Liverpool Women’s NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool, UK
Hewitt Centre for Reproductive Medicine, Liverpool Women’s NHS Foundation Trust, Liverpool, UK
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Hewitt Centre for Reproductive Medicine, Liverpool Women’s NHS Foundation Trust, Liverpool, UK
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Hewitt Centre for Reproductive Medicine, Liverpool Women’s NHS Foundation Trust, Liverpool, UK
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Liverpool Women’s NHS Foundation Trust, Member of Liverpool Health Partners, Liverpool, UK
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Optimisation of lifestyle factors such as smoking and alcohol is encouraged to improve fecundability rates in the fertility setting. Currently, routine fertility consultations do not involve counselling or imparting advice regarding habitual physical activity (PA) and/or structured exercise, despite data showing that vigorous PA can be associated with delayed time to pregnancy. Therefore, this study aimed to determine habitual PA in a sample of women attending the one-stop infertility (OSI) clinic. In total, 250 women attending a large tertiary level NHS fertility unit prospectively completed a questionnaire anonymously over a period of 9 months. The participants (mean age: 34 ± 5 years, mean BMI: 29 ± 7 kg/m2) habitual PA levels varied from vigorous exercise on ≥5 days/week (8%, n = 17) to no moderate or high-intensity activities across the whole week (66%, n = 29). A majority of women reported no structured exercise (72%, n = 179). No association was identified between any domain of PA and BMI, age, alcohol units, regular periods, or time spent trying to conceive (P > 0.05). The participants habitual PA levels varied widely and no association between any domain of PA and background of the women was identified. No existing evidence and/or guidelines to explicitly inform women attempting to conceive regarding recommended PA levels are available, despite PA being a modifiable, affordable, and feasible lifestyle choice with the possible potential to improve fertility. A large-scale, clinical trial assessing the effects of PA on fecundability is warranted to gain insight into the potential of this lifestyle factor to improve fertility outcomes and to explore the underlying biological mechanisms involved.
Lay summary
Infertility affects approximately one in seven couples with many and varied causes, including lifestyle factors such as smoking, alcohol, and diet. Lifestyle changes are low-cost unimposing options to implement in routine fertility care. Information on regular physical activity is not currently enquired from women and no agreement regarding the best levels of exercise exists for fertility patients. In this study, we aimed to determine the exercise habits of women attending the OSI clinic. In total. 250 women attending OSI clinic over a period of 9 months completed a questionnaire collecting data on their exercise habits. The levels of physical activity performed varied widely from vigorous exercise on ≥5 days/week to no moderate or high-intensity activities across the whole week. A majority of women did no structured exercise (72%). These novel data highlight the variations in form, type and intensity of exercise women who attend OSI clinics perform. Currently, there is no existing evidence and/or guidelines to explicitly inform women attempting to conceive regarding the recommended physical activity levels. Physical activity is a modifiable, affordable, and feasible lifestyle choice that is not currently acknowledged in the fertility setting and has the potential to improve fertility.
