Ovulatory cycle shifts in human motivational prioritisation of sex and food.

Previous research on the endogenous effects of ovarian hormones on motivational states in women has focused on sexual motivation. The Motivational Priority Shifts Hypothesis has a broader scope. It predicts a shift from somatic to reproductive motivation when fertile. In a highly powered preregistered online diary study across 40 days, we tested whether 390 women report such an ovulatory shift in sexual and eating motivation and behaviour. We compared 209 naturally cycling women to 181 women taking hormonal contraceptives (HC) to rule out non-ovulatory changes across the cycle as confounders. We found robust ovulatory decreases in food intake and increases in general sexual desire, in-pair sexual desire and initiation of dyadic sexual behaviour. Extra-pair sexual desire increased mid-cycle, but the effect did not differ significantly in HC women, questioning an ovulatory effect. Descriptively, solitary sexual desire and behaviour, dyadic sexual behaviour, appetite, and satiety showed expected mid-cycle changes that were diminished in HC women, but these failed to reach our strict preregistered significance level. Our results provide insight into current theoretical debates about ovulatory cycle shifts while calling for future research to determine motivational mechanisms behind ovulatory changes in food intake and considering romantic partners' motivational states to explain the occurrence of dyadic sexual behaviour.

Demographic and socio-economic correlates of knowledge of the ovulatory cycle among tribal women in India: Evidence from the nationally representative survey (NFHS-5).

BACKGROUND: The knowledge of ovulatory cycle (KOC) is the basis for natural family planning methods. The absence of knowledge is a notable issue since the ovulatory cycle plays a crucial role in reproductive health and empowers women to make informed decisions that influence their lives. This study examines the knowledge of the ovulatory cycle among reproductive tribal women in India and its demographic and socio-economic determinants. METHODS: The data were derived from the National Family Health Survey conducted in 2019-2021. The effective sample size for the present study was 1,01,914 tribal women aged 15-49 years in India. Descriptive statistics along with bivariate analysis were conducted to find the preliminary results. Additionally, multivariable binary logistic regressions were conducted to determine the likelihood of KOC among tribal women across different characteristics. We conducted statistical analysis in STATA 17.0 (StataCorp) and used ArcGIS 10.8.2 for spatial mapping. RESULTS: Out of 1,01,914 tribal women, 78.8 per cent lack correct knowledge of the ovulatory cycle. Notably, Education level significantly influences KOC, with secondary education showing higher odds of KOC (AOR: 1.24, 95% CI:1.006-1.528) compared to no education. Christian women exhibit lower odds of having KOC (AOR: 0.749, 95% CI:0.564-0.996) compared to Hindu women. Husband/partner's education level shows a strong association, with higher-educated partners correlating with higher odds of KOC (AOR: 2.501, 95% CI: 1.807-3.461) for higher education. Knowledge of any contraceptive method and current contraceptive use type are strongly associated with KOC. Additionally, rural residence negatively influences KOC (AOR: 1.545, 95% CI: 1.236-1.932), while exposure to mass media has a positive effect (AOR: 1.152, 95% CI: 0.975-1.362) albeit modest. CONCLUSION: The study highlights the need for targeted educational and awareness programs to improve KOC among tribal women in India. By addressing factors such as education, religious influences, and place of residence, we can empower these women to make informed decisions about their reproductive health, ultimately enhancing their overall well-being and quality of life. This knowledge is not only a foundation for natural family planning but also a key driver of women's agency and autonomy in shaping their lives.

Knowledge of the ovulatory cycle and its determinants among women of childbearing age in Haiti: a population-based study using the 2016/2017 Haitian Demographic Health Survey.

BACKGROUND: The knowledge of ovulatory cycle (KOC) is the base for natural family planning methods, yet few studies have paid attention to women's KOC. This study aimed to assess the prevalence of correct KOC and its determinants among women of childbearing age in Haiti. METHODS: Data from the nationally representative cross-sectional Haiti Demographic and Health Survey 2016/17 were used. STATA/SE version 14 was employed to analyse the data by computing descriptive statistics, Chi­square, and binary logistic regression model to assess the socio-economic and demographic predictors of correct KOC. P-value less than 0.05 was taken as a significant association. RESULTS: Out of 14,371 women of childbearing age who constituted our sample study, 24.1% (95% CI 23.4-24.8) had correct KOC. In addition, the findings showed that place of residence, respondent's education level, wealth index, currently working, husband/partner's education level, contraceptive use, exposure to mass media FP messages, and fieldworker visit were significantly associated with correct KOC. CONCLUSION: Policies should include increasing the literacy at community level as well as of individual women and their partners. Moreover, increasing awareness about family planning should be prioritized, especially for women from poor households and rural areas.

Exploring health insurance and knowledge of the ovulatory cycle: evidence from Demographic and Health Surveys of 29 countries in Sub-Saharan Africa.

BACKGROUND: Unplanned pregnancy continues to be a major public health concern in Sub-Saharan Africa (SSA). Understanding the ovulatory cycle can help women avoid unplanned pregnancy. Though a wide range of factors for ovulatory cycle knowledge in SSA countries has not been well assessed, the influence of health insurance on ovulatory cycle knowledge is largely unknown. As a result, we set out to investigate the relationship between health insurance enrollment and knowledge of the ovulatory cycle among women of childbearing age. This study aims to investigate the relationship between health insurance enrollment and knowledge of the ovulatory cycle among women of childbearing age in sub-Saharan Africa (SSA). METHODS: Demographic and Health Surveys (DHSs) data from 29 SSA countries were analyzed. The association between health insurance and ovulatory cycle knowledge was investigated using bivariate and multivariate multilevel logistic regression models among 372,692 women of reproductive age (15-49). The findings were presented as adjusted odds ratios (AOR) with 95% confidence intervals (CI). A p-value of 0.05 was considered statistically significant. RESULTS: The pooled result shows that the prevalence of knowledge of ovulatory cycle in the studied 29 SSA countries was 25.5% (95% CI; 24.4%-26.6%). Findings suggest higher odds of ovulatory cycle knowledge among women covered by health insurance (AOR = 1.27, 95% CI; 1.02-1.57), with higher education (higher-AOR = 2.83, 95% CI; 1.95-4.09), from the richest wealth quintile (richest-AOR = 1.39, 95% CI; 1.04-1.87), and from female headed households (AOR = 1.16, 95% CI; 1.01-1.33) compared to women who had no formal education, were from the poorest wealth quintile and belonged to male headed households, respectively. We found lower odds of ovulatory cycle knowledge among women who had 2-4 parity history (AOR = 0.80, 95% CI; 0.65-0.99) compared to those with history of one parity. CONCLUSIONS: The findings indicate that the knowledge of the ovulatory cycle is lacking in SSA. Improving health insurance enrollment should be considered to increase ovulatory cycle knowledge as an approach to reduce the region's unplanned pregnancy rate. Strategies for improving opportunities that contribute to women's empowerment and autonomy as well as sexual and reproductive health approaches targeting women who are in poorest quintiles, not formally educated, belonging to male headed households, and having high parity should be considered.

Hormones, ovulatory cycle phase and pathogen disgust: A longitudinal investigation of the Compensatory Prophylaxis Hypothesis.

Multiple studies have argued that disgust, especially pathogen disgust and contamination sensitivity, change across women's ovulatory cycle, with higher levels in the luteal phase due to an increase in progesterone levels. According to the Compensatory Prophylaxis Hypothesis (CPH), women have a higher disgust sensitivity to pathogen cues when in the luteal phase (or when progesterone levels are higher), because progesterone is associated with suppressed immune responses. Evidence for this hypothesis is rather mixed and uncertain, as the largest study conducted so far reported no compelling evidence for an association between progesterone levels and pathogen disgust. Further, ovulatory cycle research has been criticized for methodological shortcomings, such as invalid cycle phase estimates, no direct hormone assessments, small sample sizes or between-subjects studies. To address these issues and to contribute to the literature, we employed a large, within-subjects design (N = 257 with four sessions each), assessments of salivary hormone levels and cycle phase estimates based on luteinizing hormone tests. A variety of multilevel models suggest no compelling evidence that self-reported pathogen disgust or contamination sensitivity is upregulated in the luteal phase or tracks changes in women's hormone levels. We further found no compelling evidence for between-subjects associations of pathogen disgust or contamination sensitivity and hormone levels. Results remain robust across different analytical decisions (e.g. in a subsample of women reporting feeling sick). We discuss explanations for our results, limitations of the current study and provide directions for future research.

Individual and community-level determinants of knowledge of ovulatory cycle among women of reproductive age in 29 African countries: a multilevel analysis.

BACKGROUND: Knowledge of the ovulatory cycle (KOC) can help reduce the chances of unwanted pregnancies and may improve a woman's reproductive health. However, little is known about the factors associated with knowledge of the ovulatory cycle across Africa. Therefore, we aimed to investigate the individual/household and community level determinants of KOC among women of childbearing age in 29 African countries. METHODS: We used data from the Demographic and Health Surveys of 29 African countries conducted between 2010 and 2020. Bivariate and multivariate multilevel logistic regressions were used to examine the association between women's correct knowledge of the ovulatory cycle and individual/household and community-level factors. The results were reported using adjusted odds ratios (AOR) with a 95% confidence interval (CI). RESULTS: The pooled results showed that correct KOC among women was 15.5% (95% CI 14.2-17.0%), varying from 11.5% in Liberia to 57.1% in the Democratic Republic of Congo. Regarding regional distribution, the highest prevalence of KOC was observed in West Africa (38.8%) followed by East Africa (21.3%) and was lowest in Southern Africa (15.6%) and Central Africa (15.5%). After adjusting for potential confounders, at the individual level, we found the odds of KOC to be higher among older women (40-44 years-aOR 3.57, 95% CI 1.90-6.67, 45-49 years-aOR 2.49, 95% CI 1.29-4.82), and women with higher educational level (aOR 2.58, 95% CI 1.40-4.75); at the community level, higher KOC was among women exposed to media (aOR 2.24, 95% CI 1.32-3.81). CONCLUSIONS: Knowledge of ovulatory cycle among women of reproductive age was found to be low in the region and varied by country. Women's age and educational level were the individual-level factors associated with increased knowledge of ovulatory cycle while community-level media exposure was found to be associated with increased knowledge of ovulatory cycle in this study. This finding highlights the need for appropriate strategies (possibly use of mass media) to increase knowledge of ovulatory cycle among women of reproductive age, especially among adolescents in Africa.

A longitudinal evaluation of ovulatory cycle shifts in women's mate attraction and preferences.

Are ovulatory cycle shifts in women's mate attraction and preferences robust? What are underlying mechanisms of potential cycle shifts? These questions are the subject of a current scientific debate surrounding the good genes ovulatory shift hypothesis. Here, we report a large, preregistered, within-subjects study, including salivary hormone measures and conception risk estimates based on luteinizing hormone tests. In four sessions across one ovulatory cycle, N = 257 women (= 1028 sessions) rated the attractiveness of 40 natural male bodies, 40 natural female bodies and 40 objects. Multilevel analyses yielded weak evidence for ovulatory increases in women's general attraction, specifically to male bodies, though they are not systematically related to changes in steroid hormone levels. Further, we found no compelling robust evidence for mate preference shifts across the cycle, as only one out of many different tests showed some weak evidence for such effects. Mechanisms regulating cycle shifts, the impact of our results on developing and revising cycle shift theories, and influences of different methodologies on results are discussed.

Effects of controlled ovarian stimulation on vascular barrier and endothelial glycocalyx: a pilot study.

PURPOSE: Controlled ovarian stimulation significantly amplifies the number of maturing and ovulated follicles as well as ovarian steroid production. The ovarian hyperstimulation syndrome (OHSS) increases capillary permeability and fluid extravasation. Vascular integrity intensely is regulated by an endothelial glycocalyx (EGX) and we have shown that ovulatory cycles are associated with shedding of EGX components. This study investigates if controlled ovarian stimulation impacts on the integrity of the endothelial glycocalyx as this might explain key pathomechanisms of the OHSS. METHODS: Serum levels of endothelial glycocalyx components of infertility patients (n=18) undergoing controlled ovarian stimulation were compared to a control group of healthy women with regular ovulatory cycles (n=17). RESULTS: Patients during luteal phases of controlled ovarian stimulation cycles as compared to normal ovulatory cycles showed significantly increased Syndecan-1 serum concentrations (12.6 ng/ml 6.1125th-19.1375th to 13.9 ng/ml 9.625th-28.975th; p=0.026), indicating shedding and degradation of the EGX. CONCLUSION: A shedding of EGX components during ovarian stimulation has not yet been described. Our study suggests that ovarian stimulation may affect the integrity of the endothelial surface layer and increasing vascular permeability. This could explain key features of the OHSS and provide new ways of prevention of this serious condition of assisted reproduction.

CCL20-CCR6 axis directs sperm-oocyte interaction and its dysregulation correlates/associates with male infertility‡.

The interaction of sperm with the oocyte is pivotal during the process of mammalian fertilization. The limited numbers of sperm that reach the fallopian tube as well as anatomic restrictions indicate that human sperm-oocyte encounter is not a matter of chance but a directed process. Chemotaxis is the proposed mechanism for re-orientating sperm toward the source of a chemoattractant and hence to the oocyte. Chemokines represent a superfamily of small (8-11 kDa), cytokine-like proteins that have been shown to mediate chemotaxis and tissue-specific homing of leukocytes through binding to specific chemokine receptors such as CCRs. Here we show that CCR6 is abundantly expressed on human sperms and in human testes. Furthermore, radioligand-binding experiments showed that CCL20 bound human sperm in a specific manner. Conversely, granulosa cells of the oocyte-surrounding cumulus complex as well as human oocytes represent an abundant source of the CCR6-specific ligand CCL20. In human ovaries, CCL20 shows a cycle-dependent expression pattern with peak expression in the preovulatory phase and CCL20 protein induces chemotactic responses of human sperm. Neutralization of CCL20 in ovarian follicular fluid significantly impairs sperm migratory responses. Conversely, analyses in infertile men with inflammatory conditions of the reproductive organs demonstrate a significant increase of CCL20/CCR6 expression in testis and ejaculate. Taken together, findings of the present study suggest that CCR6-CCL20 interaction may represent an important factor in directing sperm-oocyte interaction.

Probing Ovulatory-Cycle Shifts in Women's Preferences for Men's Behaviors.

The existence of ovulatory-cycle shifts in women's mate preferences has been a point of controversy. There is evidence that naturally cycling women in their fertile phase, compared with their luteal phase, evaluate specific behavioral cues in men as more attractive for sexual relationships. However, recent research has cast doubt on these findings. We addressed this debate in a large, preregistered, within-participants study using salivary-hormone measures and luteinizing-hormone tests. One hundred fifty-seven female participants rated the sexual and long-term attractiveness of 70 men in dyadic intersexual interactions in natural videos. Multilevel comparisons across two ovulatory cycles indicated that women's mate preferences for men's behaviors did not shift across the cycle for either competitive or courtship behavior. Within-women hormone levels and relationship status did not affect these results. Hormonal mechanisms and implications for estrus theories are discussed.

Calcium signaling and expression of voltage-gated calcium channels in the mouse ovary throughout the estrous cycle†.

The estrous cycle is an iterative change in the anatomy, endocrinology, physiology, and behavior to provide maximum fecundity. Ovarian steroid production involves gonadotropin-induced [Ca2+]i raises due in part to voltage-gated Ca2+ channels (VGCCs) whose identity and tissue distribution in situ is largely unknown. Using fluorescence Ca2+ imaging and confocal microscopy, we recorded both spontaneous and depolarization-induced Ca2+ signals in living mouse ovarian slices. They were most prominent in theca cells (TCs) and oocytes. The presence of Ca2+ channel subunits CaV 1.2, CaV 1.3, CaV 2.1, CaV 2.2, and CaV 3 was examined with immunofluorescence of ovarian sections. CaV 1.2 and CaV 1.3 (L-type Ca2+ channels) are present in the stroma, granulosa cells (GCs), and corpora lutea (CL). Intriguingly subunits that are characteristic of nerve cells are also expressed: P/Q-type (CaV 2.1; α1A) in the stroma and CL cells and N-type (CaV 2.2; α1B) in perifollicular smooth muscle cells. The expression of α1 subunits fluctuates along the estrous cycle: in metestrus-diestrus (the quiescent stage of the cycle), CL and GCs are similarly stained, while in proestrus (stage of maximal ovarian stimulation) CL staining increases relatively to GCs. Also in proestrus, CaV 3 Ca2+ channel subunits are expressed more in CL compared to GC suggesting a more significant role of Ca2+ channels. In estrus, CaV 3 subunits from mesenchymal and interfollicular stromal cells become intensely stained. Our study represents an important step in understanding the role of VGCCs in ovarian physiology and possibly in ovarian cancer and other reproductive pathologies.

Do women's preferences for masculine voices shift across the ovulatory cycle?

Are estrous mate preference shifts robust? This question is the subject of controversy within human evolutionary sciences. For nearly two decades, mate preference shifts across the ovulatory cycle were considered an important feature of human sexual selection, directing women's attention toward mates with indicators of "good genes" in their fertile phase, when conception is possible. However, several recent studies on masculine faces, bodies and behaviors did not find evidence supporting this account, known as the good genes ovulatory shift hypothesis. Furthermore, evidence that preferences for masculine characteristics in men's voices are related to women's cycle phase and hormonal status is still equivocal. Here, we report two independent within-subject studies from different labs with large sample sizes (N = 202 tested twice in Study 1; N = 157 tested four times in Study 2) investigating cycle shifts in women's preferences for masculine voices. In both studies, hormonal status was assessed directly using salivary assays of steroid hormones. We did not find evidence for effects of cycle phase, conception risk, or steroid hormone levels on women's preferences for masculine voices. Rather, our studies partially provide evidence for cycle shifts in women's general attraction to men's voices regardless of masculine characteristics. Women's relationship status and self-reported stress did not moderate these findings, and the hormonal pattern that influences these shifts remains somewhat unclear. We consider how future work can clarify the mechanisms underlying psychological changes across the ovulatory cycle.

Egg deposition of maternal testosterone is primarily controlled by the preovulatory peak of luteinizing hormone in Japanese quail.

Differential transfer of maternal testosterone (T) into egg yolk provides a means of adjusting an offspring's phenotype to ambient environmental conditions. While the environmental and genetic driven variability in yolk T levels is widely described, the underlying mechanisms are poorly understood. Here, we investigated whether neuroendocrine mechanisms controlling ovulatory processes are associated with the regulation of yolk T deposition. Circulatory profiles of luteinizing hormone (LH), T and estradiol levels were analysed during the last 7h before ovulation in Japanese quail selected for contrasting yolk T concentrations. Moreover, the pituitary responsiveness to a single challenge with gonadotropin releasing hormone (GnRH) was evaluated. High egg T (HET) birds displayed higher concentrations of LH at 3.5h before ovulation than low egg T (LET) birds while no differences were found around the time of expected ovulation. The pre-ovulatory profile of T and estradiol levels did not differ between LET and HET females but pre-ovulatory plasma T positively correlated with LH concentrations at 6.5h and 3.5h before ovulation. The LH response to GnRH did not differ between LET and HET females. Our results demonstrate that the pre-ovulatory LH surge can determine the amount of T transferred into the egg yolk. This link between yolk T deposition and the ovulatory cycle driven variation of reproductive hormones may explain balance between the effects of circulating T on female's reproductive physiology and yolk T on offspring phenotype.

Investigating cycle shifts in women's clothing style and grooming.

In contrast to some non-human primate species, human females do not show overt cues to fertility. Previous research argued that women still show systematic changes in their appearance across their ovulatory cycle to enhance their mating success when fertile. We report five studies investigating whether women's clothing style and grooming behaviour change across the ovulatory cycle. All studies were large (with N = 157 in Study 1, N = 109 in Study 2, N = 257 in Studies 3-5), longitudinal studies with four testing sessions per participant. They involved salivary hormone samples and luteinizing hormone tests to validate conception risk estimates. Across all studies, our results suggest no compelling evidence for cycle shifts in clothing style and grooming. Rather, two studies suggest effects in the opposite direction as hypothesized, as women wore more skin-revealing clothes when non-fertile. One study suggests small effects of wearing necklaces more and eyeglasses less often when fertile. However, these effects were not robust across all studies. Our results are in line with other recent null replications and suggest that, if existent, cues to fertility might be even more subtle than previously assumed. We discuss the need for testing competing theories that explain the evolution of concealed ovulation.

Are there sex differences in oxytocin and vasopressin V1a receptors ligand binding affinities?

BACKGROUND: There is substantial evidence for sex differences in the functioning of one of the most common receptor systems; G protein-coupled receptors (GPCRs). There are many points along the GPCR-mediated molecular signaling pathway at which males and females may differ, one of the first of which, chronologically, is in the stability of the interaction between the ligand and the receptor, or its binding affinity. Here we investigate the binding affinities of oxytocin (OT) and vasopressin (AVP) at the oxytocin receptor (OTR) and the vasopressin V1a receptor (V1aR), both of which are present in numerous in brain regions associated with social behavior. METHOD: In order to investigate sex- and estrous cycle-dependent differences in ligand-receptor binding affinity, male (n = 6) Syrian hamsters (Mesocricetus auratus), females on the day of estrus (E females, n = 6), and females on the second day of diestrus (D2 females n = 6) were chosen for study. Brains from hamsters were mounted on slides and competition and saturation binding assays were conducted. RESULTS: We report a remarkable similarity in the binding affinities of OT and AVP in males and females. Small differences were detected, however, in receptor and ligand specificity in females depending on whether they were in the estrous or diestrous stage of their ovulatory cycle. CONCLUSION: These data suggest that sex differences in binding affinity are not a likely source of the many sex differences that have been observed in the effects of OT and AVP in hamsters and other species.

Revisiting the Relation Between Steroid Hormones and Unethicality in an Exploratory, Longitudinal Study With Female Participants.

Research on the relation between hormones and unethical behaviors and tendencies has provided mixed results, hindering the understanding of the potential biological regulation of unethical behaviors and tendencies. We conducted an exploratory, longitudinal study (N = 257 women) allowing to estimate relations between, on the one hand, steroid hormones (testosterone, cortisol, estradiol, and progesterone) and conception probability and, on the other hand, a broad variety of measures related to unethicality (self-reported personality variables, cheating in committed relationships, self-serving economic dishonesty in a behavioral task, namely, the mind game). Contrary to theoretical assumptions of and results from some previous studies, we find no consistent relation between hormones and unethical behavior or tendencies in the majority of analyses. Yet, some small, exploratory associations emerged that call for (preregistered) replications, before more firm conclusions can be made.

Sexual Desire of Women With Fast and Slow Life History Throughout the Ovulatory Cycle.

Findings on female sexual motivation across the ovulatory cycle are mixed. Some studies have reported increased female sexual desire on fertile days or midway through the ovulatory cycle, whereas others have reported increased sexual desire on nonfertile days. We postulated and tested the hypothesis that the pattern of the cyclical change of female sexual desire is associated with women's life history. Female participants completed life-history measures and rated their levels of sexual desire on the survey day and reported the first day of their current and subsequent cycle, respectively (Study 1), or recorded their sexual desire throughout an entire cycle by submitting daily reports (Study 2). Results indicate that women with a fast life history experienced peak sexual desire midcycle, whereas women with a slow life history experienced two peaks of sexual desire midcycle and around their menses. These findings suggest that, consistent with the underlying life history, cyclically differential peaking of sexual desire may serve different reproductive functions.

Does emotion recognition change across phases of the ovulatory cycle?

Recognizing emotions is an essential ability for successful interpersonal interaction. Prior research indicates some links between the endocrine system and emotion recognition ability, but only a few studies focused on within-subject differences across distinct ovulatory cycle phases and this ability. These studies have demonstrated mixed results that might be potentially due to heterogeneity in experimental tasks, methodologies, and lacking ecological validity. In the current study, we investigated associations between within-subject differences in ovarian hormones levels and emotion recognition from auditory, visual, and audiovisual modalities in N = 131 naturally cycling participants across the late follicular and mid-luteal phase of the ovulatory cycle. We applied a within-subject design with sessions in the late follicular and mid-luteal cycle phase, and also assessed salivary progesterone and estradiol in these sessions. Our findings did not reveal any significant difference in emotion recognition ability across two cycle phases. Thus, they emphasize the necessity of employing large-scale replication studies with well-established study designs along with proper statistical analyses. Moreover, our findings indicate that the potential link between ovulatory cycle phases (late follicular and mid-luteal) and emotion recognition ability might have been overestimated in previous studies, and may contribute to theoretical and practical implications of socio-cognitive neuroendocrinology.

Higher risk of pre-eclampsia and other vascular disorders with artificial cycle for frozen-thawed embryo transfer compared to ovulatory cycle or to fresh embryo transfer following in vitro fertilization.

Background: Risks of maternal morbidity are known to be reduced in pregnancies resulting from frozen embryo transfer (FET) compared to fresh-embryo transfer (fresh-ET), except for the risk of pre-eclampsia, reported to be higher in FET pregnancies compared to fresh-ET or natural conception. Few studies have compared the risk of maternal vascular morbidities according to endometrial preparation for FET, either with ovulatory cycle (OC-FET) or artificial cycle (AC-FET). Furthermore, maternal pre-eclampsia could be associated with subsequent vascular disorders in the offspring. Methods: A 2013-2018 French nationwide cohort study comparing maternal vascular morbidities in 3 groups of single pregnancies was conducted: FET with either OC or AC preparation, and fresh-ET. Data were extracted from the French National Health System database. Results were adjusted for maternal characteristics and infertility (age, parity, smoking, obesity, history of diabetes or hypertension, endometriosis, polycystic ovary syndrome and premature ovarian insufficiency). Results: A total of 68025 single deliveries were included: fresh-ET (n=48152), OC-FET (n=9500), AC-FET (n=10373). The risk of pre-eclampsia was higher in AC-FET compared to OC-FET and fresh-ET groups in univariate analysis (5.3% vs. 2.3% and 2.4%, respectively, P<0.0001). In multivariate analysis the risk was significantly higher in AC-FET compared to fresh-ET: aOR=2.43 [2.18-2.70], P<0.0001). Similar results were observed for the risk of other vascular disorders in univariate analysis (4.7% vs. 3.4% and 3.3%, respectively, P=0.0002) and in multivariate analysis (AC-FET compared to fresh-ET: aOR=1.50 [1.36-1.67], P<0.0001). In multivariate analysis, the risk of pre-eclampsia and other vascular disorders were comparable in OC-FET and fresh-ET: aOR=1.01 [0.87-1.17, P= 0.91 and aOR=1.00 [0.89-1.13], P=0.97, respectively).Within the group of FET, the risks of pre-eclampsia and other vascular disorders in multivariate analysis were higher in AC-FET compared to OC-FET (aOR=2.43 [2.18-2.70], P<0.0001 and aOR=1.5 [1.36-1.67], P<0.0001, respectively). Conclusion: This nationwide register-based cohort study highlights the possibly deleterious role of prolonged doses of exogenous estrogen-progesterone supplementation on gestational vascular pathologies and the protective role of the corpus luteum present in OC-FET for their prevention. Since OC-FET has been demonstrated not to strain the chances of pregnancy, OC preparation should be advocated as first-line preparation in FET as often as possible in ovulatory women.

Stability and validity of steroid hormones in hair and saliva across two ovulatory cycles.

Steroid hormones are often assessed via saliva samples, as they are noninvasive and easy to collect. However, hormone levels in saliva can fluctuate from moment-to-moment, are influenced by factors such as momentary emotional states and food intake, and some vary strongly across women's ovulatory cycle. In contrast, hormone levels in hair seem to be more robust against these influences and were previously suggested to be a good alternative to obtain women's baseline hormone levels. In the current study, we investigated whether hormone levels are stable across multiple assays and whether hormone levels from saliva and hair samples correlate. We collected saliva and hair samples from N = 155 naturally cycling women across two ovulatory cycles. All samples were analyzed for progesterone, testosterone and cortisol levels via mass spectrometry (LC-MS/MS). Results showed that both averaged saliva and hair hormone levels were moderately stable across cycles. Hair progesterone levels showed higher stability than the respective levels from saliva. Saliva and hair levels for progesterone and testosterone were moderately correlated, whereas cortisol levels from saliva and hair were only weakly correlated. Results suggest that the type of sample from which baseline hormone levels are assessed and the cycle phase in which saliva samples are collected may have a high impact on the obtained results. Implications for future studies are suggested.