Factors influencing natural fecundity in fertile couples: a survey of puerperae and their partners.

RESEARCH QUESTION: What is the fecundity rate among fertile couples, and which factors influence it? DESIGN: Retrospective study of all puerperae attending Cruces University Hospital Human Reproduction Unit over 9 months. An anonymous questionnaire was circulated to all patients, and 2510 valid completed questionnaires were collected. The main inclusion criterion was natural conception resulting in delivery. Pregnancies resulting from ART and contraceptive method failure were excluded. Investigated parameters were time to pregnancy, age and smoking (in women and men), previous pregnancies and intercourse frequency. A mathematical formula was developed to predict the per-month fecundity rate (PMFR). RESULTS: The cumulative fecundity rate was 29.08%, 54.26%, 68.61%, 89.88%, 96.95% and 98.63% (at 1, 3, 6, 12, 24 and 36 months); between 12 and 36 months, the average PMFR ranged from 8.53-7.48%. Only 1.68% of pregnancies occurred between 24 and 36 months, and only 1.37% thereafter. The best fecundity markers were obtained in the group who had sexual intercourse seven to eight times a week. Women and men younger than 25 years had lower fecundity markers than those aged between 25 and 40 years. CONCLUSIONS: Fertile couples have a non-negligible per-month fecundity rate between 12 and 36 months, which should be considered when planning fertility studies. The lower fecundity rate observed in women and men aged younger than 25 years deserves more study. Coital frequencies of more than two or three times a week did not affect the fecundity rate and was better with frequencies of seven to eight times a week.

Endometriosis affects natural and ART fertility in different ways: let's look at the whole patient and not at the single lesion.

When considering the typical lesions associated with endometriosis, such as endometriomas, and pelvic adherences involving the tubes, it is very clear how this pathology may impair both natural and assisted reproductive technology (ART) fertility. It may be more difficult for clinicians to recognize that endometriosis can reduce female fertility potential through other mechanisms which may be independent of direct damage to ovarian reserve and tubal function. The most recent clinical studies have shown that endometriosis is associated with increased risk of infertility, independent of the type of endometriosis (ovarian, peritoneal and deep endometriosis). In the IVF setting, the cumulative live birth rate in women with endometriosis has been reported to be significantly lower compared with women without endometriosis. Endometriosis is a complex, multifactorial condition that encompasses not only the presence of endometriotic lesions, but also involves women's sexuality, uterine and ovarian compartment. Endometriosis should always be considered a severe risk factor for infertility and ART failure.

Understanding the perspective of women who use the Billings Ovulation Method®: a focus group study.

BACKGROUND: The Billings Ovulation Method®(the Billings Method) is a fertility awareness-based method (FABM) of family planning that relies on the observation of patterns of fertility and infertility based on vulvar sensations and appearance of discharges. This allows people to choose when to have intercourse, depending on whether they want to avoid or achieve pregnancy. Few studies have documented user experiences with FABMs. METHODS: We conducted four virtual focus groups (FGs) in May and June 2021 with current adult women users of the Billings Method. We asked questions about users' reasons for selecting a FABM and the Billings Method, positive experiences and challenges learning and using the Billings Method, and suggestions for improving the user experience. We performed a content analysis of the transcribed FGs to explore key themes from the discussions. COREQ guidelines were followed. RESULTS: Twenty women between the ages of 23 and 43 participated in the FGs. Reasons women described choosing a FABM included to follow religious beliefs, to avoid side effects of hormonal contraception, and/or to learn more about their bodies. Reasons for selecting the Billings Method included perceiving it as more precise and easier to understand than other FABMs, having a scientific basis, and being recommended by family and friends. Experiences related to learning and using the Billings Method were mainly positive. They included finding the method easy to use and learn, successfully using it to either postpone or achieve a pregnancy and increasing their awareness of their bodies. Challenges for participants included the inherent learning curve for identifying sensations at the vulva and the required periods of abstinence. Participants provided suggestions and recommendations for improving users' experience, including raising awareness of the Billings Method among healthcare providers. CONCLUSIONS: Users of the Billings Method expressed an overall positive experience when learning and using it for family planning and body awareness. Some challenges were identified that offer opportunities to improve how the Billings Method is taught and delivered. These findings can also enhance healthcare providers' interactions with FABM users, including those of the Billings Method.

The Barren Bear Fruit: Good News for Sterile Couples.

It is estimated that between 2.1 percent and 8.3 percent of Catholic couples remain biologically childless after exhausting all morally upright approaches for assisting reproduction. This represents a significant group within the Church earnestly seeking to live a fruitful married life in the absence of conceiving children. This essay seeks to provide a theologically and pastorally enriching exploration of marital fruitfulness for sterile Catholic couples in two ways: first, by demonstrating how the meanings of human fruitfulness and sterility have been definitively transformed by Christ and second, by exploring some of the ways sterile Christian marriages are abundantly fruitful. The insights of twentieth-century theologian, Hans Urs von Balthasar are drawn upon and shaped for this purpose. The essay concludes by highlighting ways that sterile Christian couples can be supported to come to a better understanding of the abundant fruitfulness of their marriage.

Omega-3 fatty acid supplementation and fecundability.

STUDY QUESTION: Is self-reported use of omega-3 fatty acid supplements associated with fecundability, the probability of natural conception, in a given menstrual cycle? SUMMARY ANSWER: Prospectively recorded omega-3 supplement use was associated with an increased probability of conceiving. WHAT IS KNOWN ALREADY: In infertile women, omega-3 fatty acid intake has been associated with increased probability of pregnancy following IVF. In natural fertility, studies are conflicting, and no study of natural fertility has evaluated omega-3 fatty acid supplementation and fecundity. STUDY DESIGN, SIZE, DURATION: Secondary data analysis of 900 women contributing 2510 cycles in Time to Conceive (TTC), a prospective, time to pregnancy cohort study from 2008 to December 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 30-44 years, trying to conceive <3 months, without history of infertility were followed using standardized pregnancy testing. While attempting to conceive, women daily recorded menstrual cycle events and supplement and medication intake using the Cerner Multum Drug Database. Supplements and vitamins containing omega-3 were identified. Omega-3 use, defined as use in at least 20% of days in a given menstrual cycle, in each pregnancy attempt cycle was determined. A discrete-time Cox proportional hazards model was used to calculate the fecundability ratio. MAIN RESULTS AND THE ROLE OF CHANCE: Women taking omega-3 supplementation were more likely to be younger, thinner, nulligravid, white and to take vitamin D, prenatal and multivitamins compared to women not taking omega-3s. After adjusting for age, obesity, race, previous pregnancy, vitamin D and prenatal and multivitamin use, women taking omega-3 supplements had 1.51 (95% CI 1.12, 2.04) times the probability of conceiving compared to women not taking omega-3s. LIMITATIONS, REASONS FOR CAUTION: Our study was not a randomized controlled trial. The women who used omega-3 supplements may represent a more health-conscious population. We sought to address this by adjusting for multiple factors in our model. Additionally, the omega-3 fatty acid supplements that TTC participants used included multiple types and brands with varying dosages of omega-3 fatty acids. Women reported the type of supplement they were taking but not the concentration of omega-3s in that supplement. It is therefore not possible to compare dosing or a dose-response relationship in our study. WIDER IMPLICATIONS OF THE FINDINGS: Omega-3 supplementation may present a feasible and inexpensive modifiable factor to improve fertility. Randomized controlled trials are needed to further investigate the benefits of omega-3 supplementation for women trying to conceive naturally. STUDY FUNDING/COMPETING INTERESTS: This study was supported by the Division of Reproductive Endocrinology and Infertility at the University of North Carolina at Chapel Hill, the NIH/NICHD (R21 HD060229-01 and R01 HD067683-01), and in part by the Intramural Research Program of the National Institute of Environmental Health Sciences (Z01ES103333). The authors declare that there is no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

A Spring in the Desert: Infertility and Merciful Accompaniment.

The mystery of love as it unfolds in marriage is an adventure filled with wonder and anticipation for what the future holds. Such is the excitement and optimism of the couple embarking on family life by actively trying to conceive a child. For the couple struggling with infertility, however, joyful anticipation can soon devolve into anguish as they realize that their hoped-for children might not come. Though the pain of infertility is a shared experience in marriage, it is to the woman that evaluation, testing, and treatment is often directed. She may experience infertility as an assault on her feminine identity, her marriage, and her faith, leaving her vulnerable to reliance on scientific and technological solutions as the only relief for her pain. This turn toward science, if not integrated into the larger framework of overall health and well-being, has the danger of making the natural, good desire for a child into a quest to achieve a single-minded goal. When the child becomes a "goal," husband, wife, and potential offspring become (unintentionally) objectified, and the woman's identity and the future of her marriage rest precariously on the shoulders of an ideal. It is within the context of the authors' lived experience of infertility, as well as hundreds of encounters with women in the Springs in the Desert community, that the authors contend that it is necessary to integrate the pain of infertility into a framework of merciful accompaniment. Pastors, physicians, and Fertility Care Providers are all uniquely well-placed to offer support and encouragement that affirm the intrinsic dignity of the wife and her husband, and the truth of their marriage as a witness to Christ in the world. When they meet the woman amidst her pain and longing, they can help her to understand infertility as a circumstance and not her identity. When the pain of infertility is seen and acknowledged, the medical and pastoral care she receives can positively impact her overall health and wellbeing, help her to turn to her husband, and ultimately encourage her to find God in the midst of the struggle.

Misrepresentation of contraceptive effectiveness rates for fertility awareness methods of family planning.

AIM: Simplified contraceptive method-efficacy and/or typical-use effectiveness rates are commonly used for direct comparison of the various contraceptive methods. Use of such effectiveness rates in this manner is, however, problematic in relation to the fertility awareness methods (FAMs). The aim of this review is to critically examine current international representation of contraceptive effectiveness for the various FAMs in clinical use. This review also details important issues when appraising and interpreting studies on FAMs used for avoiding pregnancy. METHODS: Current international literature regarding contraceptive effectiveness of FAMs was surveyed and appraised. This included World Health Organization and Centers for Disease Control (USA) resources, key clinical studies and recent systematic reviews. Chinese literature was also searched, since these data have not been reported in the English literature. RESULTS: Reliance on certain historical studies has led to the misrepresentation of contraceptive effectiveness of FAMs by perpetuation of inaccurate figures in clinical guidelines, the international literature and the public domain. Interpretation of published study results for FAMs is difficult due to variability in study methodology and other clinical trial quality issues. Recent systematic analyses have noted the considerable issues with study designs and limitations. Several non-English published studies using the Billings Ovulation Method have demonstrated that a broader review of the literature is required to better capture the data potentially available. CONCLUSION: A deeper understanding by clinicians and the public of the applicability of contraceptive effectiveness rates of the various FAMs is needed, instead of reliance on the inaccurate conglomerate figures that are widely presented.

Serum omega-3 and omega-6 fatty acid concentrations and natural fertility.

STUDY QUESTION: Are serum omega-3 and omega-6 essential fatty acid concentrations associated with the probability of conceiving? SUMMARY ANSWER: There is no strong association between serum concentrations of omega-3 and omega-6 fatty acids and the probability of conceiving naturally. WHAT IS KNOWN ALREADY: Omega-3 and omega-6 fatty acid serum concentrations have been shown to play an important role in reproduction in animal models, while conflicting results have been reported in human studies of infertile women. It is unknown to what extent omega fatty acid serum concentrations impact natural fertility. STUDY DESIGN, SIZE, DURATION: A nested, case-control study was conducted consisting of 200 participants [fertile: conceived within 3 cycles of attempt (n = 50), subfertile: conceived within 4 and 12 cycles of attempt (n = 100) and infertile: did not conceive within 12 cycles of attempt (n = 50)] randomly selected from the Time to Conceive cohort, a prospective time-to-pregnancy study (2008 to 2015). PARTICIPANTS/MATERIALS, SETTING, METHODS: In the Time to Conceive study, women aged 30-44 years who were trying to conceive for <3 months and had no history of infertility were recruited and followed until the end of their pregnancy or ~1 year of pregnancy attempt. For this study, serum collected early in the woman's pregnancy attempt was analysed for anti-Müllerian hormone (AMH) and omega-3 and omega-6 fatty acid concentrations by liquid chromatography-mass spectrometry. The primary outcome was a positive home pregnancy test. The secondary outcomes were miscarriage and serum AMH level. A discrete-time Cox proportional hazards model was used to estimate the fecundability ratio. The odds ratios for miscarriage were calculated using logistic regression. The association between serum omega fatty acid concentrations and AMH level (natural log transformed) was analysed using Pearson's Correlation. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 200 women provided 1321 cycles for analysis.Mean omega-3, omega-6 and omega-6:omega-3 ratios did not significantly differ between the fertile, subfertile and infertile groups. There were no associations (all fecundability ratios ~1.0) between pregnancy and individual omega-3 fatty acid concentrations, including alpha-linolenic acid, eicosapentaenoic acid and docosahexaenoic acid, or omega-6 fatty acids, including linoleic acid (LA), dihommo-gamma linolenic acid and arachidonic acid. There was no significant association between any individual omega fatty acid serum concentration and the age-adjusted odds of miscarriage. No association was found between any serum omega fatty acid concentration and AMH. LIMITATIONS, REASONS FOR CAUTION: This study is limited by the sample size. Omega-3 and omega-6 fatty acid concentrations were derived from serum provided at a single timepoint in the first cycle of enrollment. Serum concentrations may therefore not be representative of all critical timepoints in the menstrual cycle or throughout their attempts to conceive. Additionally, women enrolled in this study were 30 years of age and older, and therefore the findings may not apply to younger women. WIDER IMPLICATIONS OF THE FINDINGS: These data would suggest that omega-3 and omega-6 serum levels are not associated with natural fertility or risk of miscarriage. However, due to the above-mentioned limitations, future investigation is still needed to determine whether omega-3 fatty acid supplementation may benefit women planning to conceive naturally. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Division of Reproductive Endocrinology and Infertility at the University of North Carolina at Chapel Hill, by the NIH/NICHD (R21 HD060229-01 and R01 HD067683-01) and, in part, by the Intramural Research Program of the National Institute of Environmental Health Sciences (Z01ES103333). Dr. Jukic received vitamin D supplements for a research study from Theralogix, Inc. The authors have no other conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Twins Support the Absence of Parity-Dependent Fertility Control in Pretransition Populations.

A conclusion of the European Fertility Project in 1986 was that pretransition populations mostly displayed natural fertility, where parity-dependent birth control was absent. This conclusion has recently been challenged for England by new empirical results and has also been widely rejected by theorists of long-run economic growth, where pre-industrial fertility control is integral to most models. In this study, we use the accident of twin births to show that for three Western European-derived pre-industrial populations-namely, England (1730-1879), France (1670-1788), and Québec (1621-1835)-we find no evidence for parity-dependent control of marital fertility. If a twin was born in any of these populations, family size increased by 1 compared with families with a singleton birth at the same parity and mother age, with no reduction of subsequent fertility. Numbers of children surviving to age 14 also increased. Twin births also show no differential effect on fertility when they occurred at high parities; this finding is in contrast to populations where fertility is known to have been controlled by at least some families, such as in England, 1900-1949, where a twin birth increased average births per family by significantly less than 1.

A Comparison of User Behaviors for a Fertility-Tracking App: Does Training in an NFP Method Improve Persistence and Use?

This study explores differences in the use of CycleProGo™ (CPG), a fertility-tracking app developed by Couple to Couple League (CCL), between those exposed to it as a part of natural family planning (NFP) instruction versus those who find it on their own. An anonymous data set of 17,543 CPG accounts opened between April 2013 and June 2016 was used for analysis. Nonmember users opened the most accounts (58 percent, n = 10,134), CCL members represented 38 percent (n = 6,758) of new accounts, and 207 CCL teachers (4 percent) were using CPG for personal charting. Significantly more nonmember accounts had zero days of use after the initial opening compared to CCL member accounts (61 percent vs. 23 percent, respectively, χ2 = 2,405.9, p < .001). Conversely, significantly more CCL member accounts were used for ninety days or longer than nonmember accounts (47 percent vs. 13 percent, respectively, χ2 = 2,404.2, p < .001). CCL students-those who began using the app as part of a formal NFP teaching curriculum-were more likely to use the app for > six cycles compared to nonmembers. In accounts with at least one complete cycle, CCL students were the most diligent at daily recording (95 percent of cycle days with observation recorded) followed by CCL members (88 percent) and nonmembers (76 percent). CCL teachers had the lowest frequency of cycle days with a recorded observation (73 percent). Within each cohort, accounts with > six recorded cycles had a lower proportion of cycle days with an observation recorded, likely reflecting increasing knowledge of their personal fertility patterns. Long-term users who had no known formal training in NFP still had the lowest proportion cycle days with a fertility observation. We conclude formal NFP instruction increases the probability of long-term app use, and regardless of training, long-term users will likely record observations on about 70 percent of cycle days. SUMMARY: "CycleProGo™ users with NFP training were more persistent and diligent about daily data input than those without training."

Randomness in the Bedroom: There Is No Evidence for Fertility Control in Pre-Industrial England.

Overturning a generation of research, Cinnirella et al. Demography, 54, 413-436 (2017) found strong parity-dependent fertility control in pre-Industrial England 1540-1850. We show that their result is an unfortunate artifact of their statistical method, relying on mother fixed effects, which contradicts basic biological possibilities for fecundity. These impossible parity effects also appear with simulated fertility data that by design have no parity control. We conclude that estimating parity control using mother fixed effects is in no way feasible. We also show, using the Cambridge Group data that Cinnirella et al. used, that there is no sign of parity-dependent fertility control in English marriages before 1850.

Can anti-Müllerian hormone predict success outcomes in donor sperm inseminations?

Anti-Müllerian hormone (AMH) is a useful biomarker to predict the ovarian response to controlled ovarian stimulation (COS) for IVF. However, currently there is a lack of evidence for the role of ovarian reserve markers when there is no need of COS. The aim of this study was to evaluate the usefulness of AMH to predict the outcomes of donor sperm insemination cycles in non-infertile women. A retrospective study including 139 healthy women, who underwent 348 intrauterine insemination (IUI) cycles with donor sperms under the stimulated or natural cycles, was conducted. All patients had an AMH evaluation performed before starting the first IUI attempt. AMH levels were similar in both, women who conceived and those who did not (2.00 ± 1.52 vs. 1.88 ± 1.64 ng/ml; p = .45). The area under the ROC curve in predicting pregnancy for AMH was 0.53. After adjusting for other confounding variables, the multivariate analysis revealed that AMH was not associated with pregnancy (aOR 0.89; 95% CI 0.57-1.37). We conclude that AMH is not predictive of pregnancy in healthy non-infertile women who perform IUI with donor sperm. These findings suggest the low capability of AMH to predict fertility when no COS is needed.

Mortality-fertility synergies during the demographic transition in the developed world.

The classic theory used to explain the demographic transition assumes that mortality is the key explanatory variable influencing the decline in fertility. However, the empirical results obtained in what is known as the Princeton European Fertility Project have led many specialists to question this assumption. Using both national and provincial aggregated data for 25 countries over a long time span, the analysis reported in this paper found that mortality does indeed play a fundamental role in accounting for the main demographic changes that occurred both before and during the transitional period. Others' research based on individual data has shown clearly that the number of surviving children was indeed an important factor for reproductive decisions. My analysis, using aggregated data, reached largely similar conclusions regarding the role of mortality in changing reproductive trends, via its impact on nuptiality and marital fertility at different stages of the demographic transition.

Realizing a desired family size: when should couples start?

STUDY QUESTION: Until what age can couples wait to start a family without compromising their chances of realizing the desired number of children? SUMMARY ANSWER: The latest female age at which a couple should start trying to become pregnant strongly depends on the importance attached to achieving a desired family size and on whether or not IVF is an acceptable option in case no natural pregnancy occurs. WHAT IS KNOWN ALREADY: It is well established that the treatment-independent and treatment-dependent chances of pregnancy decline with female age. However, research on the effect of age has focused on the chance of a first pregnancy and not on realizing more than one child. STUDY DESIGN, SIZE, DURATION: An established computer simulation model of fertility, updated with recent IVF success rates, was used to simulate a cohort of 10 000 couples in order to assess the chances of realizing a one-, two- or three-child family, for different female ages at which the couple starts trying to conceive. PARTICIPANTS/MATERIALS, SETTING, METHODS: The model uses treatment-independent pregnancy chances and pregnancy chances after IVF/ICSI. In order to focus the discussion, we single out three levels of importance that couples could attach to realizing a desired family size: (i) Very important (equated with aiming for at least a 90% success chance). (ii) Important but not at all costs (equated with a 75% success chance) (iii) Good to have children, but a life without children is also fine (equated with a 50% success chance). MAIN RESULTS AND THE ROLE OF CHANCE: In order to have a chance of at least 90% to realize a one-child family, couples should start trying to conceive when the female partner is 35 years of age or younger, in case IVF is an acceptable option. For two children, the latest starting age is 31 years, and for three children 28 years. Without IVF, couples should start no later than age 32 years for a one-child family, at 27 years for a two-child family, and at 23 years for three children. When couples accept 75% or lower chances of family completion, they can start 4-11 years later. The results appeared to be robust for plausible changes in model assumptions. LIMITATIONS, REASONS FOR CAUTION: Our conclusions would have been more persuasive if derived directly from large-scale prospective studies. An evidence-based simulation study (as we did) is the next best option. We recommend that the simulations should be updated every 5-10 years with new evidence because, owing to improvements in IVF technology, the assumptions on IVF success chances in particular run the risk of becoming outdated. WIDER IMPLICATIONS OF THE FINDINGS: Information on the chance of family completion at different starting ages is important for prospective parents in planning their family, for preconception counselling, for inclusion in educational courses in human biology, and for increasing public awareness on human reproductive possibilities and limitations. STUDY FUNDING/COMPETING INTERESTS: No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared.

Too old to have children? Lessons from natural fertility populations.

STUDY QUESTION: Is it possible to construct an age curve denoting the ages above which women are biologically too old to reproduce? SUMMARY ANSWER: We constructed a curve based on the distribution of female age at last birth in natural fertility populations reflecting the ages above which women have become biologically too old to have children. WHAT IS KNOWN ALREADY: The median age at last birth (ALB) for females is ∼40-41 years of age across a range of natural fertility populations. This suggests that there is a fairly universal pattern of age-related fertility decline. However, little is known about the distribution of female ALB and in the present era of modern birth control, it is impossible to assess the age-specific distribution of ALB. Reliable information is lacking that could benefit couples who envisage delaying childbearing. STUDY DESIGN, SIZE, DURATION: This study is a review of high-quality historical data sets of natural fertility populations in which the distributions of female age at last birth were analysed. The studies selected used a retrospective cohort design where women were followed as they age through their reproductive years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using a common set of eligibility criteria, large data files of natural fertility populations were prepared such that the analysis could be performed in parallel across all populations. Data on the ALB and confounding variables are presented as box and whisker plots denoting the 5th, 25th, 50th, 75th and 95th percentile distribution of the age at last birth for each population. The analysis includes the estimation of Kaplan-Meier curves for age at last birth of each population. The hazard curve for ALB was obtained by plotting the smoothed hazard curve of each population and taking the lowest hazard within a time period of at least 5 years. This lowest hazard curve was then transformed into a cumulative distribution function representing the composite curve of the end of biological fertility. This curve was based on the data from three of the six populations, having the lowest hazards of end of fertility. MAIN RESULTS AND THE ROLE OF CHANCE: We selected six natural fertility populations comprising 58 051 eligible women. While these populations represent different historical time periods, the distribution of the ages at last birth is remarkably similar. The curve denoting the end of fertility indicates that <3% of women had their last birth at age 20 years meaning that almost 98% were able to have at least one child thereafter. The cumulative curve for the end of fertility slowly increases from 4.5% at age 25 years, 7% at age 30 years, 12% at age 35 years and 20% at age 38 years. Thereafter, it rises rapidly to about 50% at age 41, almost 90% at age 45 years and approaching 100% at age 50 years. LIMITATIONS, REASONS FOR CAUTION: It may be argued that these historical fertility data do not apply to the present time; however, the age-dependent decline in fertility is similar to current populations and is consistent with the pattern seen in women treated by donor insemination. Furthermore, for reproductive ageing, we note that it is unlikely that such a conserved biological process with a high degree of heritability would have changed significantly within a century or two. WIDER IMPLICATIONS OF THE FINDINGS: We argue that the age-specific ALB curve can be used to counsel couples who envisage having children in the future. Our findings challenge the unsubstantiated pessimism regarding the possibility of natural conception after age 35 years. STUDY FUNDING/COMPETING INTEREST(S): No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared.

Effects of diabetes mellitus on sperm quality and fertility outcomes: Clinical evidence.

BACKGROUND: Diabetes mellitus is a global epidemic characterized by high morbidity and mortality. Diabetes mellitus can lead to acute and chronic systemic complications. Among them, a negative effect of diabetes mellitus on sperm quality and male/couple fertility has been suggested. However, available studies in diabetes mellitus men evaluated relatively small cohorts with discordant results. OBJECTIVES: To evaluate the clinical evidences of the effects of diabetes mellitus on sperm quality and fertility outcomes. METHODS: An extensive Medline search was performed identifying studies in the English language. RESULTS: The prevalence of diabetes mellitus in infertile men ranges from 0.7% to 1.4%, while the prevalence of infertility in diabetes mellitus men, evaluated in a few studies, ranges from 35% to 51%. Male diabetes mellitus seems to play a negative effect on couple fecundity, while being childless or subfertile men might increase the risk of diabetes mellitus. Available cross-sectional studies investigating semen parameters and male sexual hormones in men with diabetes mellitus are heterogeneous, assessed relatively small cohorts, show often discordant results and frequently are not directly comparable to derive robust conclusions. Two meta-analyses support a negative effect of diabetes mellitus on sperm normal morphology and no effect on sperm total count, with contradictory results regarding other semen parameters. Considering only studies on type 1 diabetes mellitus men, meta-analyses support a negative effect of diabetes mellitus on sperm motility and no effect on sperm total count, with contradictory results regarding other semen parameters. The rate of children observed among type 1 diabetes mellitus men was lower than controls, especially in subjects with a longer diabetes mellitus duration. Couples with a diabetes mellitus male partner undergoing assisted reproduction techniques showed lower pregnancy rates than controls. No study evaluated the impact of diabetes mellitus treatment on semen quality and male fertility. CONCLUSIONS: Overall, available data show that diabetes mellitus might impair male reproductive health and couple fertility. However, further larger and full of details studies are needed.

Survey of Long-Term Experiences of Sperm Cryopreservation in Oncological and Non-Oncological Patients: Usage and Reproductive Outcomes of a Large Monocentric Cohort.

Progress in oncological treatment has led to an improved long-term survival of young male cancer patients over the last decades. However, standard cancer treatments frequently implicate fertility-damaging potential. Cryopreservation of sperm is the current standard option to preserve patient's fertility after treatment, yet long-term data on usage and reproductive experiences is still limited. Natural fertility after treatment and especially in relation to the type of treatment has been poorly analyzed so far. Therefore, we performed a retrospective survey including male patients with an indication for gonadotoxic treatment who cryopreserved reproductive material at our institution between 1994 and 2017. Study questionnaires regarding treatment, material usage, and reproductive outcomes were sent to eligible patients. Additionally, semen analyses of study participants from the time of cryopreservation were evaluated. A total of 99 patients were included in the study. Respondents' median age was 38.0 years. Most frequent diagnoses were testicular cancer (29.3%) and lymphoma (26.3%). A further 8.1% suffered from autoimmune diseases. Testicular cancer patients had a significantly lower pre-treatment median sperm concentration (18.0 million/ml) compared to non-testicular cancer patients (54.2 million/ml). Until November 2020, the determined sperm usage and cumulative live-birth rate per couple were 17.2% and 58.8%, respectively. Most sperm users received treatments with high (40.0%) or intermediate (33.3%) gonadotoxic potential. 20.7% of all patients reported to had fathered at least one naturally conceived child after treatment, this being the case especially if they had been treated with less or potentially gonadotoxic therapies. In conclusion, our findings emphasize the importance of sperm cryopreservation in the context of male fertility preservation. Furthermore, they indicate that the gonadotoxic potential of patients' treatments could represent a predictive factor for sperm usage.

Age of Natural Menopause and Related Factors among the Tabari Cohort.

OBJECTIVES: The age of menopause is affected by several factors. In this study we aimed to identify the age of natural menopause and its related factors in a large-scale population-based cohort in Iran. METHODS: In this study, a subset of data collected during the enrollment phase of the Tabari cohort study was utilized. Reproductive history and other related data were collected using a structured questionnaire. Blood samples were obtained from all participants. Data were analyzed using chi-square test, independent t test, and ANOVA as well as a multivariate linear regression model. RESULTS: Among participants of the Tabari cohort, 2,753 were menopausal women. The mean age of natural and induced menopause was 49.2 ± 4.7 and 43.2 ± 6.4 years, respectively (P = 0.001). The number of pregnancies, duration of breastfeeding, level of education, residency, presence of thyroid disease, and body mass index affected the age of menopause. After adjustments for confounding variables, the number of pregnancies remained significantly associated with late menopause. CONCLUSIONS: The age of natural menopause in this study was similar to that in other studies, and the number of pregnancies was positively associated with the age of menopause after adjustments for confounding variables.

Prospective evaluation of luteal phase length and natural fertility.

OBJECTIVE: To evaluate the impact of a short luteal phase on fecundity. DESIGN: Prospective time-to-pregnancy cohort study. SETTING: Not applicable. PATIENT(S): Women trying to conceive, ages 30-44 years, without known infertility. INTERVENTION(S): Daily diaries, ovulation prediction testing, standardized pregnancy testing. MAIN OUTCOME MEASURE(S): Subsequent cycle fecundity. RESULT(S): Included in the analysis were 1,635 cycles from 284 women. A short luteal phase (≤11 days including the day of ovulation) occurred in 18% of observed cycles. Mean luteal phase length was 14 days. Significantly more women with a short luteal phase were smokers. After adjustment for age, women with a short luteal phase had 0.82 times the odds of pregnancy in the subsequent cycle immediately following the short luteal phase compared with women without a short luteal phase. Women with a short luteal length in the first observed cycle had significantly lower fertility after the first 6 months of pregnancy attempt, but at 12 months there was no significant difference in cumulative probability of pregnancy. CONCLUSION(S): Although an isolated cycle with a short luteal phase may negatively affect short-term fertility, incidence of infertility at 12 months was not significantly higher among these women. CLINICAL TRIAL REGISTRATION NUMBER: NCT01028365.