Showing papers in "Human Fertility in 2022"

The microbiome and male infertility: looking into the past to move forward.

Abstract: The human body harbours trillions of microbes, and their influence on human health has been explored in many parts of the human body, including the male reproductive system. From routine culturing to polymerise chain reaction (PCR) and high throughput DNA sequencing, several studies have identified bacteria in the male reproductive system. In this review, we discuss the past and current literature surrounding the testicular and semen microbiome in correlation with male infertility. We further highlight the potential benefits of probiotics as an alternative therapeutic option for male infertility. Although not conclusive, emerging data are indicating potential implications of certain bacterial members on male fertility. There is a general agreement on the negative impact of some pathogenic bacterial species on semen parameters, including sperm counts, motility, morphology, and DNA integrity. On the other hand, Lactobacillus, known as a human-friendly bacteria, has shown protective effects on semen parameters, which makes it a potentially good probiotic. In order to confirm the findings of previous studies, more clinical studies with larger sample sizes and the right controls are needed.

Fertility preservation provision in the NHS: a national assessment of care policies.

Abstract: Fertility preservation has gained momentum in recent years. As cancer survival rates improve, late effects of loss of gonadal function have increased the need to consider fertility preservation. NICE recommends offering cryopreservation of gametes or embryos to patients undergoing gonadotoxic therapy, highlighting that this should be extrapolated to those with non-malignant conditions that pose a risk to fertility. We investigated whether variation in fertility preservation provision exists across the United Kingdom, with a view to identifying equitable models of provision. In England, cryopreservation of gametes and embryos is funded for all patients undergoing treatment for cancer, but eligibility criteria and duration of storage funding vary widely. In Scotland, a national policy is applied, with health boards equitably providing funding for cryopreservation of gametes, embryos, and ovarian and testicular tissue for those undergoing treatment for benign and malignant conditions which impair fertility, including gender incongruence. In Wales and Northern Ireland, cryopreservation of gametes and embryos is funded for those undergoing treatment likely to make them infertile, but ovarian tissue cryopreservation is not funded. Funding criteria for fertility preservation in England, Wales, and Northern Ireland deviates from NICE guidance. Standardization of fertility preservation policies is needed to provide equity of access for patients.

Maternal and child-health outcomes in different endometrial preparation methods for frozen-thawed embryo transfer: a retrospective study.

Abstract: The purpose of this study was to analyse the obstetric outcome after frozen embryo transfer depending on the protocol used. The endometrial preparation during frozen embryo transfer (FET) was performed in the natural cycle (NC) with timing based on monitoring of the naturally occurring luteinizing hormone (LH) peak or in human chorionic gonadotropin (hCG)-triggered modified natural cycles (MNC), artificial cycle (AC) with hormone replacement therapy cycle and cycle with ovulation induction (OI). A retrospective cohort study was conducted between 2018 and 2020. Pregnancy, perinatal complications and neonatal outcomes were compared among patients treated during AC or MNC or OI protocols. After adjusting for the effect of gravidity, parity, pre-pregnancy body mass index (BMI) and number of miscarriages, the AC group had higher but not significantly different rates of gestational hypertension, preeclampsia and intrahepatic cholestasis of pregnancy (ICP) than women in OI and MNC groups. Significant differences were observed in the rates of placental adherence (15.30% in AC vs. 9.24% in MNC, p = 0.004) and postpartum haemorrhage (PPH) (24.33% in AC vs. 13.07% in OI, p = 0.003, 24.33% in AC vs. 16.24% in MNC, p = 0.002) among the three groups. In singletons, significant differences were observed in the rates of placental adherence (14.09% in AC vs. 8.57% in MNC, p = 0.002), AC and MNC groups had higher risk of PPH compared with OI group (18.36% in AC vs. 12.38% in MNC, p = 0.042 and 7.69% in OI vs. 18.36% in AC, p = 0.013). Neonatal outcomes were similar among the three groups except risk of small for date infants (0.35% in AC vs. 1.44% in MNC, p = 0.008). These findings are important in view of increasing use of frozen cycles and new policy of freeze-all cycles in in vitro fertilization (IVF). The results suggest a link between the absence of corpus luteum and adverse obstetric outcomes.

Sperm donors versus long-term mates: a comparison of preferences of heterosexual and lesbian women.

Abstract: The present study aimed to explore whether lesbian women's preferences for a sperm donor or a long-term mate show a pattern similar to those of heterosexual women. Three hundred and eighty-three donor insemination patients, of whom 278 were heterosexual and 105 were lesbian, completed a questionnaire comprising a series of 35 traits and rated the importance of each trait in a sperm donor and again in a long term mate. Results showed that traits relating to socioeconomic status, genetic background and general health, physical appearance, and personality were rated by lesbian women as more important in a long-term mate than in a sperm donor. It was further found that both heterosexual and lesbian women attached higher importance to the socioeconomic status, personality and physical appearance of the long-term mate than of the sperm donor; heterosexual women attached similar importance to the genes and health of a long-term mate and a sperm donor, while lesbian women attached greater importance to the genetic background and general health of the sperm donor than those of a long-term mate. The implications and interpretations of the findings are discussed in light of Trivers' parental investment theory.

Clinical features of isolated Fallopian tube torsion: evidence from a large series.

Abstract: We aimed at studying isolated Fallopian tube torsion (IFTT) in a relatively large cohort of women and to evaluate different features of IFTT in comparison to a large cohort of women with non-IFTT adnexal torsion (NIAT). This was a retrospective cohort study. We included women with surgically confirmed ovarian and/or Fallopian tube torsion between March 2011 and June 2020. Fifty-four cases of IFTT were surgically confirmed during the study period and were compared to 422 surgically confirmed NIAT. The rate of controlled ovarian hyperstimulation treatments, current pregnancy, and vomiting was lower in the IFTT group compared with the NIAT group. Cervical tenderness and vaginal discharge were more common in the IFTT group. Oedematous and enlarged ovaries were less common in the IFTT group. In multivariate regression analysis, the following factors were independently associated with IFTT: (i) vaginal discharge [adjusted odds ratio (aOR) 95% CI 8.16, 1.98-33.55]; (ii) cervical motion tenderness (aOR 95% CI 2.71, 1.01-7.29); (iii) fertility treatments (aOR 95% CI 0.26, 0.70-0.77); (iv) previous abdominal surgery (aOR 95% CI 0.46, 0.22-0.96); (v) vomiting (aOR 95% CI 0.38, 0.19-0.76); and (vi) enlarged ovary (aOR 95% CI 0.34, 0.18-0.65). In conclusion, we have identified factors positively and negatively associated with IFTT in a large cohort of women with adnexal torsion.

Chromosomal polymorphisms in assisted reproduction: a systematic review and meta-analysis.

Abstract: This systematic review and meta-analysis investigated the effects of chromosomal polymorphisms in reproductive outcomes following IVF or ICSI. Literature in CENTRAL, CINAHL, EMBASE and MEDLINE were searched from 1974 to March 2020 with no language restrictions. Ten published cohort studies were chosen for analysis. Studies included females, males and couples undergoing assisted reproductive treatments with the presence or absence of chromosomal polymorphisms. Reproductive outcomes were reported and their quality assessed using the Newcastle-Ottawa Quality Assessment Scale. Meta-analysis of five cohort studies (9,659 participants) indicated that female carriers with chromosomal polymorphisms had a higher miscarriage rate compared to non-carriers (risk ratio (RR) 1.54 (95% CI 1.19-1.98), whereas no significant association was found for males (RR 0.96, 95% CI 0.64-1.43) and couples (RR 1.93, 95% CI 0.32-11.83) indicating that this effect appeared to be gender-dependent. There was no association between chromosomal polymorphisms and a higher rate of biochemical, clinical, ongoing pregnancy, and preterm and live birth.

Does being conceived by assisted reproductive technology influence adult quality of life?

Abstract: Numerous studies have investigated the physical health and development of children and adolescents conceived with assisted reproductive technology (ART). Less is known about the quality of life of ART-conceived adults. This study explores the contributions of being conceived with ART and psychosocial cofactors present in young adulthood to the quality of life of adults aged 22-35 years. Young adults conceived through ART or natural conception (NC) completed questionnaires which included a standardized measure of quality of life (World Health Organization Quality of Life - Brief assessment (WHOQoL-BREF)) when aged 18-28 years (T1) and again when aged 22-35 years (T2). The WHOQoL-BREF has four domains: (i) Physical, (ii) Psychological, (iii) Social relationships and (iv) Environment. A total of 193 ART-conceived and 86 NC individuals completed both questionnaires. When accounting for other cofactors in multivariable analyses, being ART-conceived was strongly associated with higher scores (better quality of life) on the Social relationships, and Environment WHOQoL-BREF domains at T2. In addition, less psychological distress, a better relationship with parents, a better financial situation, and perceptions of being about the right weight at T1 were associated with higher scores on one or more of the WHOQoL-BREF domains at T2. In conclusion, being ART-conceived can confer advantages in quality of life in adulthood, independent of psychosocial cofactors.

Fertility knowledge and its related factors among married men and women in Zanjan, Iran

Abstract: Abstract This study aimed to investigate the fertility knowledge and its related factors in married men and women in Zanjan, Iran. In this cross-sectional study, 1200 individuals (including 600 women aged 18–49 years and 600 men aged 18–59 years) referred to urban and rural health centres in Zanjan, were recruited through cluster sampling from June to September 2020. The Cardiff Fertility Knowledge Scale was used to assess fertility knowledge. Data were analysed by descriptive statistical methods such as mean and standard deviation and analytical statistics, including independent sample t-test, ANOVA test, Pearson Correlation and Linear Regression were used. The average correct scores of fertility knowledge were 49.7%, 53.3%, and 51.55% for men, women, and in total, respectively. The multiple linear regression model showed that fertility knowledge was significantly related to being female, being from a higher economic status, having desire to have children in the future, and having desire to increase fertility knowledge (all p < 0.05). Fertility knowledge among the Iranian reproductive-age men and women was modest. The findings suggested that interventions to increase fertility knowledge are essential, especially interventions targeting men and lower socioeconomic groups.

Response to Boulicault et al. (2022) from women in the field

Abstract: As female scientists who have dedicated our research careers to understanding the adverse impact of environmental endocrine disrupting chemicals (EDCs) on reproductive health, we write in response to the recent article by Boulicault et al. (2022). Since the publication of Rachel Carson’s Silent Spring in 1962 (Carson, 1962), in which she noted the connection between use of the pesticide DDT and reproductive failure in wildlife, evidence that EDCs impair reproductive function and outcomes has increased exponentially. Links between EDCs and human health were still not widely accepted forty years after publication of Carson’s book when the Endocrine Society, the world’s largest medical and scientific society focussed on hormones and endocrine diseases, convened its first Forum on Endocrine Disrupting Chemicals. The goal was to review the latest evidence for EDC effects and determine if potential consequences on human health had reached critical mass. Interest in the topic was so great that the Society published its first scientific statement on EDCs in 2009 (Diamanti-Kandarakis et al., 2009). Subsequent research led to important consensus statements from other medical societies, a second statement by the Endocrine Society in 2015 and broad acceptance of the contribution of EDCs to many diseases and disorders, including reproductive dysfunctions. As in every scientific discipline, uncertainties must be acknowledged. Assessing the impact of any environmental factor on human health and disease is complex: individuals have unique genetic risk factors and lifestyle and exposure histories. This makes demonstrating cause-andeffect in humans virtually impossible, a fundamental caveat acknowledged by epidemiologists conducting research in the environmental health sciences. It is the combination of epidemiologic human data and mechanistic basic research from mainly animal models that make a compelling case that EDC exposures – especially during development – increase the likelihood of long-term and often latent disease. In their paper, Boulicault et al. (2022) challenge the interpretation that historical trends in sperm count data provide evidence of declining male fertility likely induced by growing EDC exposure. Their thesis is that the evidence of declining sperm counts published in the metaanalysis by Levine et al. (2017) is inherently flawed. Part of the basis of their critique, with which we agree, is that sperm counts are an imperfect proxy for reproductive competence. In fact, this is an exemplar of difficulties in conducting a study based on 30 years’ worth of banked data: the quality of the data may be uneven, and the population from which the data were collected may be skewed by what was or was not possible in 1973. These are inherent problems in retrospective studies. Nevertheless, sperm counts are the best (and only) possible measurement that can be used for apples-to-apples comparisons within and among populations, as well as over time, to assess male fertility. Boulicault et al. (2022) end by saying that claims that sperm count declines reflect declining fertility ‘require evidence of a causal relationship between sperm count and life historical and ecological factors...’. Because, as noted above, such causal relationships are not possible in human studies, this holds the field to an unattainable standard. Evidence from animal models, however, provide both strong causal evidence as well as mechanistic insight and evidence that EDC exposures induce a constellation of reproductive effects that include not only reduced sperm production but also male reproductive tract disorders that have increased in frequency in human populations (i.e. hypospadias, cryptorchidism and testicular cancer; collectively known as Testicular Dysgenesis Syndrome or TDS). Thus, the alternative biovariability hypothesis put forth by the authors not only is undermined by the lack of biological data to support it but also by compelling evidence for a causal relationship based on consistency between human trends and experimental data. Boulicault et al. (2022) express concern about what they view as male-centric science. This does a great disservice to our field. Effects of EDCs are not limited to males. Indeed, most of our own research is on EDC effects on female reproduction. However, a decades-long human study of the female counterpart to sperm (ova) is simply not feasible due to obvious difficulties in obtaining gamete samples from women. Thus, to date, population assessments typically have focussed on the male, something we hope will be remedied moving forward. Boulicault et al. (2022) also raise concern that the meta-analysis conducted by Levine et al. (2017) revealed significant trends only in Western countries. We believe the rationale for the separation of data into ‘Western’ and ‘other’ provided by Levine et al. (2017) is sound and that their explanation for the lack of significance in the ‘other’ group due to the small size of the available dataset from these countries is logical. Research today is far more inclusive of different races, ethnicities and

Investigation of the risk of paternal cell contamination in PGT and the necessity of intracytoplasmic sperm injection.

Abstract: ICSI is widely recommended for patients undergoing preimplantation genetic testing (PGT), but are sperm a potential source of paternal cell contamination in PGT? Semen samples were obtained from five normozoospermic men consenting to research. From each sample 1, 2, 4, 8 and 10 sperm were collected in PCR tubes and whole genome amplification according to PGT-A and PGT-SR processing protocols was undertaken. None of the 25 samples submitted (a total of 125 sperm) showed evidence of DNA amplification. Thus, paternal cell contamination resulting from using conventional in vitro fertilization (IVF) as the insemination method, carries a low risk of an adverse event or misdiagnosis in PGT-A. Due to the higher risk incurred with PGT-SR, clinics may wish to exercise increased caution and continue using ICSI, while PGT-M involves different processing protocols, presenting a different risk profile.

Identification of potential key genes related to idiopathic male infertility using RNA-sequencing data: an in-silico approach.

Abstract: Among reproductive health problems, idiopathic infertility affects married couples. The current diagnosis of male infertility focuses on the concentration, motility, and morphology of sperm in the ejaculate. Since the molecular mechanism of idiopathic infertility is unknown, identification of Differentially Expressed Genes (DEGs) among the control and idiopathic infertile male can shed light on diagnosis and treatment. Here, we analyzed the dataset GSE65683 to identify DEGs in idiopathic human sperm in three groups of patients: (i) Timed Intercourse (TIC); (ii) Intrauterine Insemination (IUI); and (iii) Assisted Reproductive Technology (ART). The enrichment analysis was carried out using DAVID (Database for Annotation, Visualization and Integrated Discovery) and GeneCodis for the DEGs. Protein-Protein Interaction (PPI) network of these DEGs were constructed using the STRING database. The network parameters such as degree and betweenness were calculated to select the important hubs. In total, 118 DEGs in TIC, 446 in IUI, and 188 in ART were identified. PPI network was constructed and identified critical top hub genes such as ACTB, BTBD6, EIF2S3, EIF3A, EIF4E, POLR2L, RPL4, RPL7, RPS11, RPL13, RPS15, RPL23, RPL27, RPL9, RPLP0 and UBA52 that may play an essential role in idiopathic male infertility. Thus, the identified hub genes may provide an insight into the molecular mechanism and contribute to discovering novel therapeutic targets and developing new strategies for idiopathic male infertility.

Motherhood and motivations for bariatric surgery – a qualitative study

Abstract: Abstract Obesity and its concomitant comorbidities have a myriad of detrimental effects on health, fertility, and quality of life. Bariatric surgery is an effective treatment for inducing weight loss and reduction of obesity-related comorbidities including subfertility. The aim of this study was to explore the expectations and experiences of women with a desire to have children as a motivation for undergoing bariatric surgery. An inductive qualitative design was used. Fourteen women were interviewed, and transcriptions were analysed with thematic analysis. Two themes emerged: (i) Motherhood and Femininity and (ii) A Normal Life. Participants found no other solution than to seek bariatric surgery to be able to become pregnant and carry a child to term. Coping physically with pregnancy and being an active mother were important factors. Overall, postoperative expectations were met, and the women experienced the effects of normalised sex hormone levels, were more physically mobile, and were released from the previous social hindrances that obesity caused them. This study has clinical implications for providing support and information to women with subfertility considering bariatric surgery and to better understand their experiences of life after bariatric surgery.

Research funding for male reproductive health and infertility in the UK and USA [2016 - 2019].

Abstract: There is a paucity of data on research funding levels for male reproductive health (MRH). We investigated the research funding for MRH and infertility by examining publicly accessible web-databases from the UK and USA government funding agencies. Information on the funding was collected from the UKRI-GTR, the NIHR's Open Data Summary, and the USA's NIH RePORT web-databases. Funded projects between January 2016 and December 2019 were recorded and funding support was divided into three research categories: (i) male-based; (ii) female-based; and (iii) not-specified. Between January 2016 and December 2019, UK agencies awarded a total of £11,767,190 to 18 projects for male-based research and £29,850,945 to 40 projects for female-based research. There was no statistically significant difference in the median funding grant awarded within the male-based and female-based categories (p = 0.56, W = 392). The USA NIH funded 76 projects totalling $59,257,746 for male-based research and 99 projects totalling $83,272,898 for female-based research Again, there was no statistically significant difference in the median funding grant awarded between the two research categories (p = 0.83, W = 3834). This is the first study examining funding granted by main government research agencies from the UK and USA for MRH. This results should stimulate further discussion of the challenges of tackling male infertility and reproductive health disorders and formulating appropriate investment strategies.

Ambivalence experienced by infertile couples undergoing IVF: a qualitative study

Abstract: Abstract The emotional consequences of infertility are well documented. However, relatively few studies have emphasized the dyadic emotional interaction within couples, despite infertility being a shared life event. This study adopted a dyadic (between two people) approach to explore the emotional complexity that infertile couples face. A descriptive qualitative study was conducted with 24 participants, including eight infertile couples and eight wives undergoing infertility treatments. Conjoint and individual interviews were conducted through purposive sampling in a large fertility centre in Tianjin, China, between June and August 2015. Thematic analysis identified two main themes: (i) ‘decisional ambivalence’, with subthemes of ‘ambivalent attitudes towards treatment’, ‘uncertainty about treatment outcomes’, and ‘treatment-related lifestyle changes’; and (ii) ‘relational ambivalence’ which included subthemes of ‘intergenerational ambivalence’ and ‘partner ambivalence’. Complex emotions of ambivalence among infertile couples were common as infertility clearly shattered their assumptive world on family formation. With complex entanglement of mixed emotions, ambivalence was intimately associated with cultural norms, social expectations, and active or over engagement of family members in Chinese societies. Since ambivalence could threaten mental and physical health during pregnancy, healthcare professionals should be prepared to assist infertile couples with identifying, articulating, and normalizing decisional and relational ambivalence during the treatment process.

The role of myo-inositol supplement in assisted reproductive techniques.

Abstract: Assisted reproductive techniques can help many infertile couples conceive. Therefore, there is a need for an effective method to overcome the widespread problems of infertile men and women. Oocyte and sperm quality can increase the chances of successful in vitro fertilisation. The maturation environment in which gametes are present can affect their competency for fertilisation. It is well established that myo-inositol (MI) plays a pivotal role in reproductive physiology. It participates in cell membrane formation, lipid synthesis, cell proliferation, cardiac regulation, metabolic alterations, and fertility. This molecule also acts as a direct messenger of insulin and improves glucose uptake in various reproductive tissues. Evidence suggests that MI regulates events such as gamete maturation, fertilisation, and embryo growth through intracellular Ca2 + release and various signalling pathways. In addition to the in-vivo production of MI from glucose in the reproductive organs, its synthesis by in vitro-cultured sperm and follicles has also been reported. Therefore, MI is suggested as a therapeutic approach to maintain sperm and oocyte health in men and women with reproductive disorders and individuals of reproductive age.

EMLA (lidocaine-prilocaine) cream for pain relief during hysterosalpingography: a systematic review and meta-analysis of randomised placebo-controlled trials.

Abstract: We systematically investigated the efficacy and safety of EMLA (5% lidocaine-prilocaine cream) versus placebo for pain relief among infertile patients undergoing hysterosalpingography (HSG). We screened four databases from inception until 25 November 2020. We included only randomised placebo-controlled trials (RCTs) and assessed their risk of bias. The main efficacy outcomes included safety and pain scores during the different stages of HSG. The pooled outcomes were summarised as mean difference (MD) with 95% confidence interval (CI). Three RCTs were included, comprising 258 patients (131 and 127 patients received EMLA and placebo, respectively). All RCTs revealed an overall low risk of bias. EMLA significantly reduced pain perception during cervical instrumentation of tenaculum and cannula (MD = -1.53, 95% CI [-2.59, -0.47], p = 0.005) and at 24 h after completion of HSG (MD = -1.30, 95% CI [-2.57, -0.03], p = 0.04). Despite EMLA decreased pain perception during the other procedural stages of HSG, the differences were not statistically significant compared with placebo. EMLA was safe and free of local and systemic adverse reactions. This meta-analysis advocates that topical application of 5% EMLA cream is safe and correlates with decreased pain perception during HSG, particularly during the cervical instrumentation step and at 24 h after HSG completion.

Recombinant human granulocyte colony stimulating factor (rhG-CSF) participates in the progression of implantation via the hsa_circ_0001550-miRNA-mRNA interaction network.

Abstract: Inadequate endometrial receptivity is a key factor affecting the successful implantation of embryos. Recombinant human granulocyte colony stimulating factor (rhG-CSF) can increase endometrial thickness and improve the outcomes of assisted reproductive technologies (ARTs). In this preliminary study, the function and possible molecular mechanisms of recombinant human granulocyte colony stimulating factor (rhG-CSF) which affects endometrial receptivity and implantation in human Embryonic Stem Cells (hESCs) were investigated. The cell viability of endometrial stromal cells treated with rhG-CSF 0.5 ng/ml for 24 h was significantly increased. Moreover, the expression of hsa_circ_0001550 was downregulated in endometrial stromal cells treated with rhG-CSF. Furthermore, the hsa_circ_0001550-miRNA-mRNA network was constructed and the downstream target genes (including 4 miRNAs and 117 mRNAs) of hsa_circ_0001550 were mainly involved in the cAMP and calcium signalling pathways, which play important roles in regulating endometrial receptivity and embryo implantation. We conclude that rhG-CSF participates in the regulation of embryo implantation by regulating the hsa_circ_0001550-miRNA-mRNA interaction network.

The effect of alpha lipoic acid supplementation on sperm functions in idiopathic asthenozoospermic patients: a case-controlled study.

Abstract: Alpha-lipoic acid (ALA) is a natural short chain fatty acid containing sulfhydryl groups generated from octanoic acid and cysteine in the mitochondria, and is found in both the aqueous and lipid phases. The present study aimed to assess the efficacy of ALA supplementation in primary infertile males complaining of idiopathic asthenozoospermia. Eighty patients were randomly allocated to treatment group A (n = 40) and control group B (n = 40) groups, receiving daily doses of 600 mg (divided into two daily doses of 300 mg each) of alpha lipoic acid (ALA) or an identical placebo for 90 days. Semen analysis, anthropometric and total antioxidant capacity were analysed and compared before and after treatment. Daily supplementation with ALA improved total motility and progressive motility of the spermatozoa. In the ALA-treated group, sperm motility and progressive motility increased significantly, similarly, the mean percentage of sperm vitality demonstrated a significant increase among the ALA treated group (p < 0.001). Analysis revealed a statistically significant increase in semen volume and sperm concentration in the ALA supplemented group, while abnormal morphology decreased significantly (p < 0.001). ALA supplementation significantly improved sperm parameters and functional tests in group A patients. ALA supplementation in patients with idiopathic asthenozoospermic thus enhanced sperm quality and viability, which could therefore be considered as an adjunct therapy pending further verification of its association and mechanisms involved.

Sperm toxicity testing on lubricant gels: should we be recommending 'fertility-friendly' specialist products?

Abstract: Couples trying to conceive or providing samples for Assisted Reproductive Technologies (ART) are advised against the use of lubricant-gels due to the risk of sperm-toxicity. However, gels now exist which are specifically formulated to help couples conceive but without consensus on their toxicity relative to non-specialist products. This study tested gels recently introduced as 'sperm friendly' (FertilSafe Plus, Fertile Check) alongside established lubricants intended for pleasure only using a recently published toxicity testing regime. Computer Assisted Sperm Analysis (CASA) was performed at 1 and 2 h on donor sperm (n = 12) pre-incubated with each gel (10% v/v) and controls. All gels led to a significant loss of motility/velocity at 1 and 2 h (p < 0.01), with the most significant loss from the 2 Durex pleasure products (11% and 15%, vs 47% progression) at 60 min, although these performed better than saliva (used as negative control). Incubation with FertilSafePlus led to the smallest loss of motility (24% vs 47%) at 1 h. Saliva and products designed for lubrication only exhibited the most negative effect on motility and those marketed as 'sperm safe' could be considered the best performers. Whether these affects are due to direct toxicity or are indirect due to other factors such as viscosity, pH or osmolality remains uncertain.

Estimation of follicular growth—widely used, seldom studied

Abstract: We assessed whether estimation of follicular growth, rather than actual measurement of follicular size on the day of hCG trigger, affected pregnancy rates in intrauterine insemination (IUI) cycles. Patient and cycle characteristics were extracted from an existing database. Comparisons were made between the pregnant (defined as a positive beta hCG) and non-pregnant groups for the following variables: patient's age, number of previous IUI cycles, type of ovarian stimulation, endometrial thickness, number of follicles measuring 14 mm and above, pre and post wash sperm parameters, cycle day when IUI was done and number of days between last ultrasound scan and ovulation trigger. A total of 7302 cycles were included in the final analysis. In 4055 cycles (55.5%) the hCG trigger was on the day of the last ultrasound, in 2285 cycles (31.3%) the hCG trigger was 1 day after the last ultrasound, in 850 (11.6%) it was 2 days after the last ultrasound and in 112 (1.5%) it was 3 or more days after the last ultrasound. Sperm parameters, younger maternal age, and the number of follicles above 14 mm were all associated with pregnancy. No association was found between positive pregnancy test rates and the time from last ultrasound to hCG trigger. Planning IUI based on the estimation of follicular growth 1-4 days before trigger, does not affect pregnancy rates.

Lessons from 10 years' experience running the Fiom KID-DNA database, a voluntary DNA-linking register for donor-conceived people and donors in The Netherlands.

Abstract: Worldwide, there is increasing acknowledgment of the importance of getting access to ancestry information. More and more countries facilitate access to this information through law changes and voluntary contact-services. In the Netherlands, the state-funded Fiom KID-DNA database was established in 2010 to facilitate information and/or contact exchange between those people who are genetically related as a result of donor-assisted conception. By the end of 2021, 846 donors and 2355 donor-conceived people are registered in the database. For 25% of the donors a link was found with one or more donor-conceived people, and 39% of the donor-conceived people were linked to a donor-profile. Fiom offers support by professionally qualified staff throughout the entire process from registration to contact to donor-conceived people, donors and their relatives. During the period of more than 10 years several challenges emerged; how does a state-funded DNA database function in the area of commercial DNA databases?; what can be learned from the continuous growing donor-conceived half-siblings networks?; how to deal with malpractices from the past and how to cope with ageing donors?

Donor sperm treatment: the role of semen parameters in intracervical insemination, a retrospective cohort study.

Abstract: Donor sperm treatment is advised to be performed with frozen-thawed donor semen. A disadvantage of frozen-thawed semen is lower pregnancy rates compared to inseminations with fresh semen. Semen parameters affect ongoing pregnancy rates in intracervical inseminations with frozen-thawed donor semen. In an attempt to translate this into clinical relevance, cohort studies have tried to find cut-off values for semen parameters after thawing for intracervical insemination, but these studies assessed only one semen parameter per study, thereby overlooking the intricate interplay between all semen parameters. We performed a retrospective cohort study and tried to calculate thresholds for all semen parameters that lead to the best possible ongoing pregnancy rates in intracervical insemination with frozen-thawed donor semen. Between April 1999 and December 2015, data from 1,186 women who underwent 7,103 cycles of intracervical insemination with donor semen from 129 sperm donors were available for analysis. Our results showed that total motility and total motile count (TMC) after thawing were associated with ongoing pregnancy rate. The best possible ongoing pregnancy chances after intracervical insemination were obtained at a total motility of ≥20% and a total motile count (TMC) of ≥8 × 106 after thawing.

Simultaneous transfer of one good-quality and one poor-quality cleavage stage embryo does not improve pregnancy outcomes.

Abstract: Embryo quality and quantity are key factors that determine the success of IVF-ET. Yet it is still unclear if, for those patients with only one good-quality embryo in an IVF cycle, the inclusion of a poor-quality embryo increases the procedure's success rate. This is a common question for both clinicians and patients in determining their course of treatment. The purpose of this work was to answer this intriguing question in the context of prognosis of patients undergoing fresh cycles with only one good-quality and more than one poor-quality cleavage-stage embryos. To control for confounding effects, we only included patients at similar age, body mass index (BMI), level of basal follicle stimulating hormone (FSH) and endometrial thickness from January 2015 to June 2021. A propensity score-matched analysis was performed to extract the matched pairs. Then we evaluated pregnancy outcome, including the rate of clinical pregnancy, live birth, embryo implantation, early miscarriage, and ectopic pregnancy. We found that the clinical pregnancy rate (34.8 vs. 38.0%, p = 0.553), live birth rate (27.1 vs. 29.9%, p = 0.598), early miscarriage rate (18.1 vs. 9.5%, p = 0.171) and ectopic pregnancy rate (1.3 vs. 1.2%, p = 1.000) did not significantly differ between those two groups, notwithstanding significant difference of the implantation rate (34.8 vs. 21.3%, p <0.001). Our work indicates that, for prognosis patients at approximately 34 years old with only one good-quality embryo, having additional poor-quality embryos does not seem to help to improve ART success rates per intended embryo transfer. In conclusion, we found that simultaneous transfer of one good-quality and one poor-quality cleavage stage embryo does not improve pregnancy outcomes.

Evaluation of PGK2 and ACR proteins in seminal plasma: suggestion of potential new biomarkers for prediction of sperm retrieval in non-obstructive azoospermia patients.

Abstract: This study aimed to assess the role of testis-specific proteins, PGK2 and ACR, in the prediction of sperm retrieval results by microdissection testicular sperm extraction (micro-TESE) in men with non-obstructive azoospermia (NOA). This was a case-control study including 48 semen samples of NOA patients undergoing the micro-TESE procedure, 15 semen samples from normozoospermic men as the positive control, and 12 semen samples from obstructive azoospermia/post-vasectomy (OA/PV) as negative controls. We investigated the levels of PGK2 and ACR proteins by ELISA tests in seminal plasma samples. The ELISA results revealed a significantly higher concentration of PGK2 and ACR in the NOA patients with successful sperm retrieval (NOA+) in comparison to NOA patients with failed sperm retrieval (NOA-) group (p = 0.0001 in both cases). For the first time, the data from this study suggests that a seminal PGK2 concentration of 136.3 pg/ml and ACR concentration of 21.75 mIU/ml can be used as cut-off values for the prediction of micro-TESE outcomes in NOA patients. These findings may be useful to avoid unnecessary micro-TESE operations. Overall, the seminal levels of the PGK2 and ACR proteins may be useful in predicting sperm retrieval success by micro-TESE in NOA patients.

Clomiphene citrate priming increases sensitivity during ovarian stimulation in poor ovarian responders undergoing <i>in vitro</i> fertilization treatment: a retrospective cohort study

Abstract: This single-centre retrospective cohort study aimed to investigate whether a clomiphene citrate (CC) priming protocol could increase ovarian sensitivity in poor ovarian responders. It included 294 patients (374 ovarian stimulation cycles). Of these, 193 cycles were treated by a CC priming antagonist protocol (study group) and 181 by the classical flexible gonadotropin-releasing hormone antagonist protocol (control group). Stimulation data and laboratory and clinical outcomes were compared between the groups. The results showed that in the study group, total gonadotropin dosage and dosage per follicle were considerably lower, the follicle-to-oocyte index was significantly higher, and the gonadotropin duration was shorter. After adjusting for potential confounders, multivariate regression analysis showed that cumulative ongoing pregnancy remained comparable between the groups (adjusted odds ratio: 0.761, 95% confidence interval: 0.300-1.933, p = 0.566). Age, body mass index, gonadotropin dosage per follicle, and the follicle-to-oocyte index were negatively associated with the reproductive outcomes. The result of the sensitivity analysis showed that patients in the study group were administered less gonadotropin at a lower gonadotropin dosage per follicle and for a shorter duration. In conclusion, the CC priming antagonist protocol offered a convenient and patient-friendly way to increase ovarian sensitivity during ovarian stimulation in poor ovarian responders.