Distribution and hormonal regulation of membrane progesterone receptors β and γ in ciliated epithelial cells of mouse and human fallopian tubes

<p>Abstract</p> <p>Background</p> <p>The controlled beating of cilia of the fallopian tube plays an important role in facilitating the meeting of gametes and subsequently transporting the fertilized egg to its implantation site. Rapid effects of progesterone on ciliary beat frequency have been reported in the fallopian tubes of cows, but the identity of the receptors mediating this non-genomic action of progesterone is not known. We recently identified a member of the non-genomic membrane progesterone receptor family, mPR gamma, as a candidate for mediating these actions of progesterone. Here, we investigated the possible presence of a related receptor, mPR beta, in the fallopian tubes of mice and women as well as the possible hormonal regulation of mPR beta and gamma.</p> <p>Methods</p> <p>Western blot and immunohistochemistry with specific antibodies were used to characterize the expression and cellular localization of the mPRs in mouse and human tissues. Taqman (Quantitative Polymerase Chain Reaction) assays were used to quantify mRNA levels in the fallopian tubes of two different mouse models after injections with different hormones and specific antagonists.</p> <p>Results</p> <p>In the fallopian tubes of both mouse and human, the expression of mPR beta and mPR gamma proteins was exclusively found in the ciliated cells. Whereas mPR beta was found on the cilia, mPR gamma was localized at the base of the same ciliated cells, as previously reported. In gonadotropin-primed mice, both mPRs genes were down-regulated after an injection with progesterone. Treatment with estradiol rapidly down-regulated the level of mPR beta mRNA and protein in immature mice. The mPR gamma protein was down-regulated around the time of ovulation in cycling women, similar to the regulation observed in mice stimulated to ovulate via gonadotropin injections.</p> <p>Conclusion</p> <p>Our findings show the presence and hormonal regulation of two distinct mPRs associated with the cilia of the fallopian tubes in both mice and women. It is hypothesized that these receptors are involved in the control of ciliary movement and, thus, gamete transport in the fallopian tubes of mammals.</p

Dietary and/or physical activity interventions in women with overweight or obesity prior to fertility treatment : protocol for a systematic review and individual participant data meta-analysis

Funding Information: This project is partly supported by the Centre for Research Excellence in Women's Health in Reproductive Life (app1171592) through a project support grant. RW is supported by a National Health and Medical Research Council (NHRMC) Investigator grant (2009767). LM is supported by a Heart Foundation Future Leader Fellowship. Funding Information: AH reports consultancy for Ferring with respect to the development of a lifestyle app. BWM is supported by an NHMRC Investigator grant (GNT1176437). BWM reports personal fees from ObsEva and Merck, and travel support from Merck, outside the submitted work. RW reports grants from the NHMRC. TM is supported by a Future Leader in Diabetes Award from the European Foundation for the Study of Diabetes/Novo Nordisk Foundation (NNF19SA058975) and grants from the regional health authority in Central Norway. ATK reports personal fees from Merck for lectures. The other authors do not have competing interest to declare. Funding Information: This project is partly supported by the Centre for Research Excellence in Women’s Health in Reproductive Life (app1171592) through a project support grant. RW is supported by a National Health and Medical Research Council (NHRMC) Investigator grant (2009767). LM is supported by a Heart Foundation Future Leader Fellowship. Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Peer reviewedPublisher PD

Elective single embryo transfer

The aim of the study was to evaluate if the elective single embryo transfer (eSET) strategy couldmaintain delivery rates, with at least one live born child, and at the same time decrease the rate ofmultiple births. A cost-effectiveness analysis was also performed between the elective single embryotransfer (SET) (1+1) and double embryo transfer (DET) (2+0) strategies. Another aim was toinvestigate whether it is possible, in a large randomized trial, to identify specific maternal and/orembryo variables that could independently predict ongoing implantation in IVF/ICSI.The study was a prospective randomized multicentre trial performed at five Swedish, four Danish andtwo Norwegian clinics. Patients under 36 years of age undergoing their first or second IVF cycle,resulting in at least two good-quality embryos, were randomized into two groups; one group received afresh eSET and if a live birth did not follow, a frozen SET and the other group received a DET on oneoccasion. Self-reporting questionnaires and medical records were collected to assess the obstetric andpaediatric outcomes and the costs. Two questionnaires were used to assess the quality of life of themothers. In the paper on predictors of ongoing implantation (n=521), an analysis was performed ofcycles with 0% or 100% ongoing implantation and with embryos transferred on day two, regardingmaternal and embryo variables.In the SET group a cumulative live birth rate of 128/330 (38.8%) was observed as compared with theDET group 142/331 (42.9%) (Difference 4.1%; 95% CI 3.4-11.6).The rates of multiple births in thetwo groups were 1/330 (0.8%) in SET and 49/331 (34.5%) in DET (p&lt;0.0001). The complicationsduring pregnancy and delivery were significantly lower in the SET group, as was the rate of Caesareansections. The children in the SET group had statistically higher mean gestational ages, lower rates ofpremature birth (&lt;37 weeks), higher mean birth weights and lower rates of low birth weight (&lt;2500 g)as compared with those in the DET group. Perinatal morbidity was markedly higher in the DET group,and the children in the DET group had significantly more days of treatment in a neonatal ward. Theincremental cost-effectiveness ratio (ICER) was SEK 675,053 per extra delivery (n=14) in the DETgroup. Mean total cost for maternal and paediatric health care was SEK 87,434 in the SET group andSEK 115,768 in the DET group. When including the costs for loss of productivity the costs were SEK102,492 and SEK 137,935, respectively. In the paper concerning predictors of ongoing implantation,in the univariate analysis, first IVF cycle, conventional IVF as fertilization method and four-cellembryos showed a statistically higher ongoing implantation rate than did second IVF cycle, ICSI andnon-four cell embryos. In the multivariate analysis the same variables and also ovarian sensitivity,expressed as number of IU of FSH per oocyte retrieved, correlated independently to ongoingimplantation.In conclusion, the SET group achieved a rate of live birth not substantially lower than was achievablewith DET and with a lower rate of maternal and paediatric complications, especially premature births.The single embryo transfer strategy resulted in better cost-effectiveness than DET and can berecommended for good prognosis women in order to decrease the twin rate

Is pre-implantation genetic diagnosis (PGD) more of a strain regarding satisfaction with marital quality for male or female partners? A three-year follow-up study

Introduction: Men and women with a hereditary genetic disease are faced with different options when they plan to become parents. One is pre-implantation genetic diagnosis (PGD) which is a combination of in vitro fertilization (IVF) and genetic analysis of the embryo before implantation. The present study focuses on how men and women planning for PGD experience the quality of marital satisfaction when they apply for treatment and again, three years later. Methods: The study was a prospective cohort study where all couples (n = 22) applying for PGD during 2010 and 2011 were eligible. Nineteen women and 17 men (i.e. 17 couples and two women) participated. Participants answered several questionnaires (Dyadic Adjustment Scale, Hospital Anxiety and Depression Scale and Parental Stress Questionnaire) before PGD treatment, and again three years later. Results: Women who underwent PGD rated the quality of their marital relationship similarly to that of first-time parents and IVF couples, whereas men rated the marital quality somewhat lower than the contrasts groups. Satisfaction with marital quality was stable over the three-year period although men were less satisfied than women on both occasions. At year three, there was a significant correlation between martial satisfaction and parental stress in men, and between martial satisfaction and anxiety and depression in women. Discussion: Men are equally, or more, affected by their situation than their female partners, with consequences for satisfaction with marital quality. For this reason they should be included in any counselling offered

The association between body mass index and live birth and maternal and perinatal outcomes after in-vitro fertilization: a national cohort study

ObjectiveTo investigate the association between female body mass index (BMI) and live birth rates and maternal and perinatal outcomes after in-vitro fertilization (IVF).MethodsWe performed a national, population-based cohort study including women undergoing IVF between 2002 and 2020. The cohort included 126,620 fresh cycles and subsequent frozen embryo transfers between 2007 and 2019 (subpopulation 1) and 58,187 singleton deliveries between 2002 and 2020 (subpopulation 2). Exposure was female BMI (kg/m2) categorized according to the World Health Organization as underweight (&lt;18.5), normal weight (18.5–24.9, reference), overweight (25.0–29.9), class I obesity (30.0–34.9), class II obesity (35.0–39.9), and class III obesity (≥40.0). The primary outcome in subpopulation 1 was cumulative live birth per started fresh IVF cycle, including fresh and subsequent frozen embryo transfers. Primary outcomes in subpopulation 2 were hypertensive disorders of pregnancy and preterm birth at less than 37 weeks. Risk ratios (RRs) with 95% confidence intervals (CIs) for the association between BMI class and outcomes were calculated using generalized linear models after adjustment for relevant confounders.ResultsThe cumulative live birth rate decreased significantly with increasing BMI from 32.6% in normal-weight women to 29.4% in overweight women, 27.0% in women in obesity class I, 21.8% in women in obesity class II, and 7.6% in women in obesity class III. The risk of hypertensive disorders of pregnancy increased significantly and progressively with increasing BMI, from 4.6% in normal-weight women to 7.8% in overweight women and 12.5%, 17.9%, and 20.3% in women in obesity classes I, II, and III. The risk of preterm birth followed a similar pattern, from 6.3% in normal-weight women to 7.5% in overweight women and 8.9%, 9.9%, and 15.3% in women in obesity classes I, II, and III. The risks of other perinatal complications, such as perinatal death, showed an even more pronounced increase.ConclusionUsing a large and complete national cohort of women undergoing IVF, we demonstrate a dose-dependent decrease in live birth rate and a substantial increase in maternal and perinatal complications with increasing BMI. Strategies to improve this situation are warranted

The number of oocytes retrieved during IVF : A balance between efficacy and safety

STUDY QUESTION: What is the relationship between the number of oocytes collected in fresh IVF treatments and the likelihood of cumulative delivery rate (fresh and frozen) per oocyte aspiration, severe ovarian hyperstimulation syndrome (OHSS) and thromboembolic events? SUMMARY ANSWER: Cumulative delivery rate per aspiration increases up to 20 oocytes retrieved and then evens out while the incidence of severe OHSS increases more rapidly from around 18 oocytes and thromboembolic events, although rare, occurs in particular if 15 or more oocytes are retrieved. WHAT IS KNOWN ALREADY?: Previous studies have shown that the number of oocytes retrieved for IVF is a positive predictor of live birth in fresh cycles. Few studies have investigated cumulative live birth rates and OHSS in relation to the number of aspirated oocytes. STUDY DESIGN, SIZE, DURATION: Retrospective population-based registry study including 39 387 women undergoing 77 956 fresh IVF cycles in the period 2007-2013 and 36 270 consecutive transfers of frozen/thawed embryos in the period 2007-2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from The Swedish National Quality Registry of Assisted Reproduction (Q-IVF) including all IVF cycles with oocyte retrieval performed in public or private infertility clinics during the study period, was cross-linked to the National Patient Register regarding diagnostic codes (ICD 10) for severe (OHSS) and thromboembolic events. Oocyte donation cycles were excluded. MAIN RESULTS AND THE ROLE OF CHANCE: Live birth delivery rate in fresh cycles increased up to 11 oocytes retrieved and then evened out, where the live birth rate was 30.3% for a 34-year-old woman. The cumulative delivery rate per aspiration, including fresh transfer and all subsequent transfers of frozen-thawed embryos (FET cycles) per oocyte retrieval, increased up to approximately 20 oocytes where it reached 45.8%. The adjusted odds ratio (AOR) for live birth by the number of oocytes was 1.064 (95% CI: 1.061; 1.067). The incidence of severe OHSS increased significantly by the number of oocytes, particularly if more than 18 oocytes were retrieved. The AOR for OHSS by the number of oocytes was 1.122 (95% CI: 1.08; 1.137). Thromboembolic events were rare, a total of 16 events in 14 patients were observed, and occurred in particular if 15 or more oocytes were retrieved. LIMITATIONS, REASONS FOR CAUTION: All FET cycles might not be included. Some embryos cryopreserved between 2010 and 2013 might still result in additional births until 2018. Furthermore the gonadotrophin dose was not included in the Q-IVF Registry in the study period, thus adjustment for dose was not possible. WIDER IMPLICATIONS OF THE FINDINGS: The results suggest a shift at approximately 18-20 oocytes where the cumulative delivery rate per aspiration levels off and, at the same time, the incidence of severe OHSS increases more rapidly. Thromboembolic events, although rare, should also be taken into consideration at stimulation regimes for IVF. Evaluating data taking both efficacy and the most serious safety aspects into account, is a new approach and of crucial importance both for patients undergoing IVF and their physicians. STUDY FUNDING/COMPETING INTEREST: Financial support was received through an agreement relating to research and the education of doctors (ALFGBG-70 940) and grant from the Hjalmar Svensson Research Foundation. None of the authors declares any conflict of interest

Obstetric outcome in singletons after in vitro fertilization with cryopreserved/thawed embryos

There is increasing use of cryopreservation in IVF. This study compared singletons born after cryopreservation with singletons born after fresh IVF cycles and singletons born to women in the general population. Data were collected for Swedish IVF treatments during the years 20022006. All singletons from single embryo transfer (SET) and double embryo transfer (DET) after cryopreserved (n 2348) and fresh cycles (n 8944) were included and cross-linked with the Swedish Medical Birth Registry and compared with all singletons born after spontaneous conception (n 571 914). Main outcomes were preterm and very preterm birth and low and very low birthweight (VLBW). Other outcomes were small for gestational age, large for gestational age (LGA), perinatal mortality and maternal outcomes. Singletons from cryopreserved SET/DET or cryopreserved SET had increased rates of extreme preterm birth compared with singletons from the general population. A lower rate of LBW was found for cryopreserved SET/DET singletons compared with singletons from fresh cycles; however, a higher rate of perinatal mortality was detected. The rates of LGA and macrosomia were increased for cryopreserved SET/DET singletons when compared with those from fresh cycles and the general population. For maternal outcomes, a higher rate of pre-eclampsia was noted for pregnancies from cryopreserved cycles compared with those from fresh cycles or the general population, but the rate of placenta praevia was lower in pregnancies from cryopreserved cycles compared with those from fresh cycles. The obstetric outcome of singletons after cryopreservation was slightly poorer when compared with the general population. In comparison with fresh cycles, the outcome varied. The finding of an increased rate of LGA after cryopreservation requires further study

A New Beginning : Young Women's Experiences and Sexual Function 18 Months After Bariatric Surgery

Introduction: Female patients expect improved quality of life, including sexual health and regain of fertility after bariatric surgery. Little has been published on to the extent to which patients’ expectations are met by the weight loss after surgery. Aim: To explore how women perceive the effects of bariatric surgery on quality of life, focusing on sexual health and fertility. Methods: A qualitative study based on thematic analysis, supported by questionnaire data. Interviews following a semistructured guide were conducted with childless women (n = 11) aged 25–34 years recruited from a university-affiliated Swedish bariatric center. The interviews took place 18 months after surgery in the participants’ homes or at the hospital and were recorded and transcribed verbatim. Data were analyzed with a thematic approach. Questionnaires were filled in at the time of the interviews and compared with preoperative data using a Wilcoxon test for paired data. Main outcome measures: Participants described experiences related to female sexual health after bariatric surgery. The Hospital Anxiety and Depression Scale and the Female Sexual Function Index questionnaires were administered preoperatively and postoperatively. Results: “A new beginning” was identified as the master theme, with 3 underlying subthemes: “Being worthy of love,” “Exploring sexuality,” and “Considering parenthood.” The participants described a transformation into being more comfortable with themselves that affected all areas of life, including sexual life. These findings were supported by lower scores for depression, 6.5 vs 2, and improved total Female Sexual Function Index scores, median 23.3 preoperatively and 29.1 postoperatively, P = .012. Conclusions: Improved body image and enhanced self-esteem play important roles in improved sexual functioning in women after bariatric surgery. Nilsson-Condori E, Järvholm S, Thurin-Kjellberg A, et al. A New Beginning: Young Women's Experiences and Sexual Function 18 Months After Bariatric Surgery