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Charvi Kanodia, Michael P Rimmer, Kathleen Duffin, and Rod T Mitchell
Lay Summary of Letter
Men and boys with cancer treated with chemotherapy are known to have reduced fertility following their treatment. This is because some chemotherapy drugs can damage the cells in the testicles that make sperm. This study found there is limited information available on the effect of one group of chemotherapy drugs, called taxanes, on testicular function and fertility. More studies are needed to aid clinicians in advising patients on how this taxane-based chemotherapy may affect their future fertility.
Yorain Sri Ranjan, Nida Ziauddeen, Beth Stuart, Nisreen Alwan, and Ying Cheong
Endometriosis is a chronic and debilitating condition which can affect the entire reproductive life course of women with a potentially detrimental effect on pregnancy. Pregnancy (and increasing parity) can affect endometriosis by modulating disease severity and suppressing symptoms. Multiparous women could be less likely to suffer from endometriosis related pregnancy complications than primiparous women. We aimed to systematically review the evidence examining the role of parity in the relationship between pregnancy outcomes and endometriosis. A systematic search of MEDLINE, EMBASE, CINAHL, Web of science and Cochrane library was performed from inception to May 2022. We searched for experimental and observational studies. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to assess the quality of evidence with the risk of bias in non-randomised studies of interventions (ROBINS-I) tool incorporated. Eleven studies were included in the meta-analysis. Primiparous women with endometriosis had almost double the risk of hypertensive disorders of pregnancy (OR 1.99, 95%CI 1.50-2.63, P <0.001) compared to multiparous women with endometriosis. Primiparous women with endometriosis were at significantly increased risk of preterm delivery, caesarean delivery, and placenta praevia compared to primiparous women without endometriosis. There were no significant differences in outcomes when multiparous women with endometriosis were compared to multiparous women without endometriosis. There is limited evidence to suggest that primiparous women with endometriosis maybe at higher risk of adverse pregnancy outcomes compared to multiparous women. The modulatory role of parity in the pathophysiology of endometriosis and impact on pregnancy outcomes should be investigated.
Yu-Fei Yang, Jia-Hao Wu, Run-Lan Lin, Shang-Jun Yin, Guoying Qian, Wei Wang, and Yong-Doo Park
The Chinese soft-shelled turtle, Pelodiscus sinensis (Reptilia: Trionychidae) is a typical seasonal breeding species and its spermatogenesis pattern is complex. In this study, the process of sperm cell development was studied using histology. The process of sperm cell development may be divided into six stages based on a combination of different cell types in the seminiferous epithelium. A close examination revealed two patterns of sperm cell development in the seminiferous tubules during the breeding season. The first is a normal sperm cell development pattern, in which the process of sperm cell development and maturation are completed in the seminiferous epithelium without round spermatozoa in the lumen. The second is rapid sperm cell development, in which the first batches of round spermatozoa fall off the seminiferous epithelium before they mature, thus beginning a second batch of sperm cell development. The round sperm cells are shed into the lumen and further mature in the seminiferous tubules and epididymis. This rapid sperm cell development process of the Chinese soft-shelled turtle is rare in other vertebrate species and may be an adaptation to cope with seasonal breeding. The results of this study provide insight into the theory of seasonal reproduction in reptiles.
Velez Carolina, Clauzure Mariangeles, Williamson Delia, Garcia Monica, Koncurat Mirta, and Barbeito Claudio
In the present work, we emphasize the studies about integrins and their receptors in pig placental interface at different times of gestation. Uterine placental interface (n = 24) of 17, 30, 60 and 70 days of gestation (dg) and non-pregnant uterus (n = 4) of crossbred sows were used. The presence of αvβ3 (ITGAV (integrin subunit alpha V) ITGB3 (integrin subunit beta 3)) and α5β1 (ITGA5 (integrin subunit alpha V) ITGB3 (integrin subunit beta 3)) integrins, and their ligands fibronectin (FN) and osteopontin (OPN/ SPP1), was detected by immunohistochemistry, and the immunolabeled area percentage (IAP) and the optical density (OD) were determined. The integrins and its ligands analyzed have presented peaks of expression in early and mid-gestation, both in IAP and in the OD area, decreasing at 70 dg. These temporal changes showed us that the molecules studied in this work participate in embryo/feto–maternal attachment, variably. Besides, we found a significant correlation both in the intensity and in the extension of immunostaining for trophoblastic FN and endometrial αvβ3, and trophoblastic OPN and endometrial α5β1, throughout the entire pig pregnancy. At late gestation, there is notable placental remodeling with subsequent removal or renewal of folds at the uterine–placental interface that results in the loss of focal adhesions. The decrease of the expression of some integrins and their ligands in late gestation, particularly at 70 dg, would demonstrate that there would be other adhesion molecules and other ligands that could be participating in the establishment of the maternal–fetal interface.
Lay summary
To carry a successful pregnancy, the formation of the placenta in pigs depends on adhesion molecules. Some of these molecules called integrins bind to other molecules such as fibronectin (FN) and osteopontin (OPN/SPP1). The variation in those molecule amounts during gestation would indicate which molecule is participating and what role it plays in pregnancy. We worked with pig placentas of early, mid- and late- gestation and non-pregnant uteruses. αvβ3 (ITGAV (integrin subunit alpha V) ITGB3 (integrin subunit beta 3)) and α5β1 (ITGA5 (integrin subunit alpha 5) ITGB1 (integrin subunit beta 1)) integrins, FN and OPN were found until mid-gestation but not at late gestation, suggesting that other types of molecules have a role in the last period of gestation.
Noof Abdulrahman Alrabiah, Constantine A Simintiras, Alexander C O Evans, Patrick Lonergan, and Trudee Fair
Follicular fluid (FF), a product of vascular transudate and granulosa and thecal cell secretions, is the milieu that has evolved to support oocyte growth and maturation which plays a central role in oocyte quality determination. Therefore, a suboptimal FF composition may be reflected in compromised oocyte progression through maturation, fertilization, or embryo development. To date, the composition of bovine FF remains understudied. To address this, we comprehensively characterized the metabolomic constituency of bovine FF in the period during which the oocyte undergoes meiotic maturation. More specifically, FF from pre (−24 h) and peri (−2 h)-ovulatory follicles was profiled by high-throughput untargeted ultra-HPLC tandem mass spectroscopy. A total of 634 metabolites were identified, comprising lipids (37.1%), amino acids (30.0%), xenobiotics (11.5%), nucleotides (6.8%), carbohydrates (4.4%), cofactors and vitamins (4.4%), peptides (3.6%), and energy substrates (2.1%). The concentrations of 67 metabolites were significantly affected by the stage of follicle development, 33.3% (n = 21) were reduced (P ≤ 0.05) by a mean of 9.0-fold, whereas 46 were elevated (P ≤ 0.05) by a mean of 1.7-fold in peri- vs pre-ovulatory FF. The most pronounced individual metabolite concentration decreases were observed in hypoxanthine (98.9-fold), xanthine (65.7-fold), 17β-oestradiol (12.4-fold), and inosine (4.6-fold). In contrast, the greatest increases were in retinal (4.9-fold), 1-methyl-5-imidazoleacetate (2.7-fold), and isovalerylcarnitine (2.7-fold). This global metabolomic analysis of bovine FF temporal dynamics provides new information for understanding the environment supporting oocyte maturation and facilitating ovulation that has the potential for improving oocyte quality both invivo and in vitro.
Lay Summary
The ovaries are part of the female reproductive system, and they produce and store eggs in structures known as ‘follicles’. Depending on the species, one or more follicles release an egg from the ovary during ovulation. FF, which is formed from the secretions of follicle cells and substances delivered from the bloodstream, bathes the eggs as they develop within their follicles. For pregnancy to happen, the egg must be capable of being fertilised by a sperm cell, developing into an embryo and implanting it in the womb. FF has evolved to support the egg to achieve this. Using the cow as a model, this study looks at the composition of FF during the final hours before ovulation, when the egg becomes mature and ready for fertilisation. More than 600 different substances were identified, providing new information, that has the potential to improve egg quality.
Dareen Mattar, Warakorn Cheewasopit, Moafaq Samir, and Phil G Knight
Kisspeptin, a hypothalamic neuropeptide encoded by the KISS1 gene, has a pivotal role in promoting gonadotrophin-releasing hormone secretion in mammals. Kisspeptin and its receptor (KISS1R) are also expressed in certain peripheral tissues including gonads, suggesting intra-gonadal roles. Such actions at the level of the bovine ovary have not been explored previously. The current aims were to determine whether KISS1 and KISS1R are expressed in the bovine ovary and whether kisspeptin or a kisspeptin antagonist can modulate ovarian steroid production by cultured ovarian cells. Granulosa cells (GC) and theca interna cells (TC) were collected from antral follicles (3–18 mm) categorized into five class sizes. Early, mid and regressing corpora lutea (CL) were also collected for RT-qPCR analysis of KISS1 and KISS1R expression. Bovine TC and GC cultured under both non-luteinizing (serum-free) and luteinizing (serum-supplemented) conditions were treated for 4 days with kisspeptin-10 (10– 10–10– 6M) or kisspeptin antagonist (kp234; 10–10–10–6M), alone and in combination with either follicle-stimulating hormone (GC), luteinizing hormone (TC) or forskolin (luteinized GC/TC). Steroid secretion (GC: oestradiol, progesterone; TC: androstenedione, progesterone; luteinized GC/TC: progesterone) was measured by ELISA and viable cell number determined by neutral red uptake assay. KISS1 and KISS1R transcripts were detected in TC, GC and CL with significant differences between follicle categories and CL stages. However, neither kisspeptin-10 nor kisspeptin antagonist affected steroid secretion or viable cell number in any of the four ovarian cell culture models. As such, the hypothesis that kisspeptin has a direct intraovarian role to modulate follicular or luteal steroidogenesis, or cell proliferation/survival, is not supported.
Lay summary
Kisspeptin-producing nerve cells (neurones) in the hypothalamus play a crucial role in controlling the reproductive system. Kisspeptin activates receptors on gonadotrophin-releasing hormone neurones which, in turn, stimulate the pituitary gland to release gonadotrophins. Gonadotrophins act on the gonads (ovaries or testes) to regulate their function (e.g. ovarian follicle development and steroid production). Evidence has emerged in several species that kisspeptin and its receptor are also present in certain peripheral tissues, including the ovaries, suggesting ‘local’ actions. So far, few studies have investigated this. Here, we first show that both kisspeptin and its receptor are expressed by key ovarian cell types of cattle. However, we found that treating cultured bovine theca and granulosa cells with kisspeptin or kisspeptin antagonist did not modify steroid secretion. As such, the hypothesis that kisspeptin has a direct intraovarian role to modulate ovarian steroid production is not supported.
Mohamed Elkalyoubi, Larissa Schindler, and Hena Zaheer
Treatment of sub-fertile women aged ≥ 40 years old (advanced maternal age (AMA)) is challenging. Co-treatment with growth hormone (GH) is suggested to improve reproductive outcomes in poor responders. However, few studies, and with conflicting results, focused on women of AMA. A systematic review and meta-analysis of randomized controlled trials (RCTs) and comparative retrospective trials (CRTs) of GH cotreatment in AMA women undergoing in vitro fertilization or intracytoplasmic injection treatment using their autologous oocytes was performed. The search included studies published in English up to the end of 2021. The primary outcome was the clinical pregnancy rate per embryo transfer. Secondary outcomes were the number of mature and retrieved oocytes and the rate of live birth. A total of 406 studies were found. The final analysis included 3 RCTs and 4 CRTs with 481 patients who used GH and 400 patients who did not. Clinical pregnancy and live birth rates were significantly higher in the GH cotreatment group compared to the placebo as well as the group without GH co-treatment, (odds ratio (OR): 2.2; 95% CI: 1.34–3.61 and OR: 4.12; 95% CI: 1.82–9.32, respectively). Intriguingly, the subgroup analysis showed that poor-responder patients did not benefit from co-treatment with GH. There were no statistically significant differences in the number of mature or retrieved oocytes. GH cotreatment in a subgroup of women of AMA improves clinical pregnancy and live birth per fresh embryo transfer. However, this conclusion must be taken with caution and further research is needed. The review is registered in the PROSPERO database (www.crd.york.ac.uk/prospero/; CRD42021252618).
Lay summary
Women over 40 years undergoing in vitro fertilization (IVF) treatment commonly require high doses of injectable medications to stimulate their ovaries. Co-treatment with growth hormone (GH) has been shown to enhance the ovarian response and improve the outcome. The investigators found seven studies that compared 881 women over 40 years of age who had undergone IVF treatment with or without GH cotreatment. Statistical analysis of data from these studies showed that some of these women may benefit from adding a GH to their ovarian stimulation medications. The benefit was evident in those with good ovarian reserve. Women over 40 years with a good ovarian reserve can increase their chance of pregnancy by 4–20% when using GH during ovarian stimulation. However, this finding requires confirmation in a well-designed study with large sample size. Furthermore, the optimal dose, regimen, safety, and cost-effectiveness of GH cotreatment should be clarified.
Bethany Chung, Charlotte Greene, Alice Pearson, Lisa M Starrs, and W Colin Duncan
Lay Summary
During the COVID-19 pandemic, the public delayed seeking medical help, which may have affected the impact of having an ectopic pregnancy. An ectopic pregnancy is when pregnancy tissue grows outside its normal position in the womb, and it can be life-threatening. It can be treated by non-surgical or surgical options, and any delay in seeking help can reduce the options for treatment and increase the need for more urgent management. We wanted to assess whether there were differences in the presentation and management of ectopic pregnancies in a major teaching hospital between 2019 (pre-COVID-19) and 2021 (COVID-19 period). We found that the pandemic did not cause a delay in seeking medical help or cause worse outcomes. In fact, immediate surgical treatment and time in the hospital were less during COVID-19, perhaps because of a desire to avoid admission to hospital. One outcome of COVID-19 is reassurance that we can safely use more non-surgical treatments for ectopic pregnancies.