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Human Reproduction (Oxford, England) Jun 2024Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin...
A modified flexible GnRH antagonist protocol using antagonist early cessation and a gonadotropin step-down approach improves live birth rates in fresh cycles: a randomized controlled trial.
STUDY QUESTION
Can pregnancy outcomes following fresh elective single embryo transfer (eSET) in gonadotropin-releasing hormone (GnRH) antagonist protocols increase using a gonadotropin (Gn) step-down approach with cessation of GnRH antagonist on the day of hCG administration (hCG day) in patients with normal ovarian response?
SUMMARY ANSWER
The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on the hCG day is effective in improving live birth rates (LBRs) per fresh eSET cycle.
WHAT IS KNOWN ALREADY
Currently, there is no consensus on optimal GnRH antagonist regimens. Studies have shown that fresh GnRH antagonist cycles result in poorer pregnancy outcomes than the long GnRH agonist (GnRHa) protocol. Endometrial receptivity is a key factor that contributes to this phenomenon.
STUDY DESIGN, SIZE, DURATION
An open label randomized controlled trial (RCT) was performed between November 2021 and August 2022. There were 546 patients allocated to either the modified GnRH antagonist or the conventional antagonist protocol at a 1:1 ratio.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Both IVF and ICSI cycles were included, and the sperm samples used were either fresh or frozen from the partner, or from frozen donor ejaculates. The primary outcome was the LBRs per fresh SET cycle. Secondary outcomes included rates of implantation, clinical and ongoing pregnancy, miscarriage, and ovarian hyperstimulation syndrome (OHSS), as well as clinical outcomes of ovarian stimulation.
MAIN RESULTS AND THE ROLE OF CHANCE
Baseline demographic features were not significantly different between the two ovarian stimulation groups. However, in the intention-to-treat (ITT) population, the LBRs in the modified antagonist group were significantly higher than in the conventional group (38.1% [104/273] vs. 27.5% [75/273], relative risk 1.39 [95% CI, 1.09-1.77], P = 0.008). Using a per-protocol (PP) analysis which included all the patients who received an embryo transfer, the LBRs in the modified antagonist group were also significantly higher than in the conventional group (48.6% [103/212] vs. 36.8% [74/201], relative risk 1.32 [95% CI, 1.05-1.66], P = 0.016). The modified antagonist group achieved significantly higher implantation rates, and clinical and ongoing pregnancy rates than the conventional group in both the ITT and PP analyses (P < 0.05). The two groups did not show significant differences between the number of oocytes retrieved or mature oocytes, two-pronuclear zygote (2PN) rates, the number of embryos obtained, blastocyst progression and good-quality embryo rates, early miscarriage rates, or OHSS incidence rates (P > 0.05).
LIMITATIONS, REASONS FOR CAUTION
A limitation of our study was that the subjects were not blinded to the treatment allocation in the RCT trial. Only women under 40 years of age who had a good prognosis were included in the analysis. Therefore, use of the modified antagonist protocol in older patients with a low ovarian reserve remains to be investigated. In addition, the sample size for Day 5 elective SET was small, so larger trials will be required to strengthen these findings.
WIDER IMPLICATIONS OF THE FINDINGS
The modified GnRH antagonist protocol using the Gn step-down approach and cessation of GnRH antagonist on hCG day improved the LBRs per fresh eSET cycle in normal responders.
STUDY FUNDING/COMPETING INTEREST(S)
This project was funded by grant 2022YFC2702503 from the National Key Research & Development Program of China and grant 2021140 from the Beijing Health Promotion Association. The authors declare no conflicts of interest.
TRIAL REGISTRATION NUMBER
The RCT was registered in the Chinese Clinical Trial Registry; Study Number: ChiCTR2100053453.
TRIAL REGISTRATION DATE
21 November 2021.
DATE OF FIRST PATIENT’S ENROLLMENT
23 November 2021.
PubMed: 38942602
DOI: 10.1093/humrep/deae145 -
Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry.Human Reproduction (Oxford, England) Jun 2024What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course...
STUDY QUESTION
What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester?
SUMMARY ANSWER
In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages.
WHAT IS KNOWN ALREADY
Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL.
STUDY DESIGN, SIZE, DURATION
The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth.
MAIN RESULTS AND THE ROLE OF CHANCE
One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01).
LIMITATIONS, REASONS FOR CAUTION
Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered.
WIDER IMPLICATIONS OF THE FINDINGS
Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system.
STUDY FUNDING/COMPETING INTEREST(S)
The research received no specific funding, and the authors declare no competing interests.
TRIAL REGISTRATION NUMBER
clinicaltrial.gov NCT05557201.
PubMed: 38942601
DOI: 10.1093/humrep/deae146 -
Computers in Biology and Medicine Jun 2024The uterus is the most important organ in the female reproductive system. Its shape plays a critical role in fertility and pregnancy outcomes. Advances in medical...
BACKGROUND
The uterus is the most important organ in the female reproductive system. Its shape plays a critical role in fertility and pregnancy outcomes. Advances in medical imaging, such as 3D ultrasound, have significantly improved the exploration of the female genital tract, thereby enhancing gynecological healthcare. Despite well-documented data for organs like the liver and heart, large-scale studies on the uterus are lacking. Existing classifications, such as VCUAM and ESHRE/ESGE, provide different definitions for normal uterine shapes but are not based on real-world measurements. Moreover, the lack of comprehensive datasets significantly hinders research in this area. Our research, part of the larger NURSE study, aims to fill this gap by establishing the shape of a normal uterus using real-world 3D vaginal ultrasound scans. This will facilitate research into uterine shape abnormalities associated with infertility and recurrent miscarriages.
METHODS
We developed an automated system for the segmentation and alignment of uterine shapes from 3D ultrasound data, which consists of two steps: automatic segmentation of the uteri in 3D ultrasound scans using deep learning techniques, and alignment of the resulting shapes with standard geometrical approaches, enabling the extraction of the normal shape for future analysis. The system was trained and validated on a comprehensive dataset of 3D ultrasound images from multiple medical centers. Its performance was evaluated by comparing the automated results with manual annotations provided by expert clinicians.
RESULTS
The presented approach demonstrated high accuracy in segmenting and aligning uterine shapes from 3D ultrasound data. The segmentation achieved an average Dice similarity coefficient (DSC) of 0.90. Our method for aligning uterine shapes showed minimal translation and rotation errors compared to traditional methods, with the preliminary average shape exhibiting characteristics consistent with expert findings of a normal uterus.
CONCLUSION
We have presented an approach to automatically segment and align uterine shapes from 3D ultrasound data. We trained a deep learning nnU-Net model that achieved high accuracy and proposed an alignment method using a combination of standard geometrical techniques. Additionally, we have created a publicly available dataset of 3D transvaginal ultrasound volumes with manual annotations of uterine cavities to support further research and development in this field. The dataset and the trained models are available at https://github.com/UL-FRI-LGM/UterUS.
PubMed: 38941903
DOI: 10.1016/j.compbiomed.2024.108794 -
Social Science & Medicine (1982) Jun 202415-20% of identified pregnancies result in miscarriage, which may lead to persistent symptoms of psychological morbidities in some women. Healthcare satisfaction is...
OBJECTIVE
15-20% of identified pregnancies result in miscarriage, which may lead to persistent symptoms of psychological morbidities in some women. Healthcare satisfaction is among the factors believed to influence such negative psychological responses. Here, we present the results of a study conducted in Portugal that analyzes the relationship between healthcare satisfaction, information and support provision and perinatal grief symptoms.
METHODS
In a cross-sectional study, symptoms of perinatal grief, degree of satisfaction with healthcare received, and information and support provision data were collected through an online survey aimed at women in Portugal who suffered a miscarriage. 873 were considered eligible. Correlations were performed between perinatal grief scores and healthcare satisfaction rates. Finally, the proportions of information and support received were compared after distributing the sample in groups according to their perinatal grief levels.
RESULTS
Healthcare satisfaction correlated significantly with perinatal grief scores, the latter increasing as satisfaction levels decreased. 61.1% of our sample received information about the physical consequences of miscarriage and showed a significantly lower rate of above-threshold perinatal grief symptoms in this group. 18.2% received information about its mental health consequences, with no significant differences in above-threshold symptom rates. 11.7% were offered or recommended mental health support, but no significant differences in above-threshold symptom rates were found.
CONCLUSION
Healthcare satisfaction and information on after-miscarriage physical changes correlated significantly with reduced perinatal grief rates after miscarriage. However, any effects of mental health information and psychological support provision need further studies. Training for healthcare providers dealing with pregnancy loss, implementing national guidelines that include follow-up on the parents' physical and psychological health, and including a specialized area in medical structures are advised.
PubMed: 38941727
DOI: 10.1016/j.socscimed.2024.117037 -
Journal of Preventive Medicine and... Jun 2024A substantial proportion of women experience mental health challenges during pregnancy or the postpartum period. Common mental disorders (CMDs), including depression,...
OBJECTIVES
A substantial proportion of women experience mental health challenges during pregnancy or the postpartum period. Common mental disorders (CMDs), including depression, anxiety, and obsessive-compulsive disorder, are prevalent. Identifying causes and associated risk factors is imperative for early intervention and the prevention of mental health issues.
METHODS
This study utilized data from the 2018 Basic Health Research, which was conducted nationwide in Indonesia, using a cross-sectional approach. We focused on women aged 13-49 years who were currently or previously married, and had experienced pregnancy, including 8,889 pregnant women and 77,012 women who had delivered between January 1, 2013, and August 31, 2018. The Self-Reporting Questionnaire-20 was employed to assess CMDs. Multivariate logistic regression was performed.
RESULTS
The prevalence of CMDs in pregnant women was 12.6%, while postpartum mothers exhibited a prevalence of 10.1%. Poor health status displayed the strongest impact on CMDs during both pregnancy (Adjusted Odds Ratio [AOR]: 12.23, 95% Confidence Interval [CI]: 9.06-16.60) and the postpartum period (AOR: 16.72, 95% CI: 14.85-18.82). Additional significant factors for both group include young maternal age, lack of education, unemployment, hystory of hypertension, and smoking status. Among pregnant women, CMDs was also associated with first-trimester pregnancy, previous pregnancy complications, and small upper arm circumference. For postpartum mothers, significant factors include history of abortion, unwanted pregnancy, pregnancy complications, lack of antenatal care, spontaneous delivery, postpartum complications and contraceptive use.
CONCLUSIONS
CMDs can impact in pregnant and postpartum women. Early diagnosis and management must be seamlessly integrated into primary healthcare practices.
PubMed: 38938048
DOI: 10.3961/jpmph.24.082 -
BMC Psychiatry Jun 2024This scoping review sought to investigate the association between pregnancy-related complications and post-traumatic stress disorder (PTSD) among postpartum women, then... (Review)
Review
OBJECTIVE
This scoping review sought to investigate the association between pregnancy-related complications and post-traumatic stress disorder (PTSD) among postpartum women, then summarize effective psychological interventions for pregnancy-related PTSD or sub-PTSD.
METHOD
Publications in English and Chinese were searched in PubMed, Embase, Cochrane, ISI Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang databases using the subject headings of "Stress Disorders, Post-Traumatic", "Pregnant Women", and "psychotherapy". To ensure that as many relevant studies are incorporated as possible, free terms such as prenatal, postnatal, perinatal and gestation were also used. Intervention studies and related cases published by July 1st, 2023, were also searched.
RESULTS
Twenty-one articles (including 3,901 mothers) were included in this review. Evidence showed that typical psychological interventions exhibited great effect, and family support programs, peer support, online yoga, and music therapy were also effective in reducing risk and improving the psychological well-being of the studied population.
CONCLUSION
Fetal abnormalities, miscarriage, premature birth, infants with low birth weights, hypertension, pre-eclampsia, HELLP syndrome, and hyperemesis gravidarum are associated with an increased risk of PTSD. Moreover, high-risk pregnant women may benefit from psychological interventions such as cognitive behavioral therapy (CBT). It may also be feasible and well-accepted for music therapy and exposure therapy to lessen the intensity of PTSD in mothers.
Topics: Humans; Pregnancy; Stress Disorders, Post-Traumatic; Female; Pregnancy Complications; Psychosocial Intervention; Psychotherapy
PubMed: 38937748
DOI: 10.1186/s12888-024-05926-6 -
Fertility and Sterility Jun 2024Menstruation serves as an indicator of women's reproductive well-being and plays a pivotal role in their fertility; nevertheless, there remains an ongoing debate... (Review)
Review
IMPORTANCE
Menstruation serves as an indicator of women's reproductive well-being and plays a pivotal role in their fertility; nevertheless, there remains an ongoing debate regarding the epidemiological evidence linking menstrual characteristics and fertility.
OBJECTIVE
To explore the correlation between menstrual characteristics and fertility in women of reproductive age.
DATA SOURCES
A comprehensive literature search was conducted using PubMed, Embase, Web of Science, and Cochrane libraries to identify research articles published up until 9 February 2024.
STUDY SELECTION AND SYNTHESIS
We included all studies in which the relationship between menstrual characteristics and pregnancy rates among women of reproductive age was investigated. We excluded studies involving the administration of oral contraceptives, application of assisted reproductive technologies, and individuals with a documented history of infertility or partners with a known history of infertility.
MAIN OUTCOMES
Clinical pregnancy and miscarriage.
RESULTS
This meta-analysis was composed of nine studies involving a total of 399,966 women, and the evidential quality derived from these studies was deemed to be high with a low risk of bias. Compared with a normal menstrual cycle length (2532 days), the impact of a short (<25 days) or long (>32 days) menstrual cycle on a woman's pregnancy was relatively insignificant (OR=0.81, CI [0.65, 1.01], I=68%; OR=0.89, CI [0.75, 1.06], I=60%, respectively); however, a change in cycle length may increase the risk of miscarriage (RR=1.87, CI [1.11, 3.15], I=0%; RR=1.66, CI [1.07, 2.57], I=43%, respectively). In comparison to women experiencing menarche at a typical age (1214 years), those with a late age at menarche (>14 years) exhibited a decreased likelihood of pregnancy (OR=0.92, CI [0.91, 0.93], I=0%); and compared with women experiencing a normal duration of menstrual bleeding (47 days), those with a short duration of menstrual bleeding (<4 days) exhibited reduced fertility potential (OR=0.86, CI [0.84, 0.88], I=29%).
CONCLUSION AND RELEVANCE
Short and long menstrual cycle lengths may elevate women's susceptibility to spontaneous abortion, whereas late age at menarche and short duration of menstrual bleeding appear to be linked to diminished fertility among women of reproductive age.
PubMed: 38936536
DOI: 10.1016/j.fertnstert.2024.06.016 -
PloS One 2024Chronic endometritis (CE), an inflammatory condition characterized by plasma cell infiltration within the endometrial stroma, is prevalent among women experiencing... (Observational Study)
Observational Study
Chronic endometritis (CE), an inflammatory condition characterized by plasma cell infiltration within the endometrial stroma, is prevalent among women experiencing unexplained infertility or recurrent miscarriages. CE is traditionally diagnosed by endometrial biopsy using CD138 immunohistochemistry staining. Despite some studies suggesting hysteroscopy as an alternative diagnostic tool, its reliability compared with biopsy remains controversial. This study evaluated the diagnostic accuracy of hysteroscopy for CE by examining endometrial features, such as congestion, micropolyps, edema, and polyps, and comparing these with biopsy-confirmed cases of CE. This retrospective observational study was conducted at Toho University Omori Medical Center between June 2017 and November 2019 and included patients undergoing both hysteroscopy and histopathological examination. Endometrial congestion was identified as the only hysteroscopic finding significantly associated with CE, showing a moderate diagnostic agreement with biopsy results. These findings highlight the importance of further investigating hysteroscopic features of CE and their diagnostic implications and identify endometrial congestion as a potential predictive marker for CE.
Topics: Humans; Female; Endometritis; Hysteroscopy; Adult; Endometrium; Retrospective Studies; Chronic Disease; Biopsy; Middle Aged
PubMed: 38935687
DOI: 10.1371/journal.pone.0303041 -
The Australian & New Zealand Journal of... Jun 2024Part II of the Australasian guideline for the investigation and management of recurrent pregnancy loss (RPL) provides evidence-based guidance on the management of RPL...
Part II of the Australasian guideline for the investigation and management of recurrent pregnancy loss (RPL) provides evidence-based guidance on the management of RPL provided. The implications of inherited and acquired thrombophilia with respect to RPL and suggestions for clinical management are provided. Autoimmune factors, including human leukocyte antigen, cytokines, antinuclear antibodies and coeliac antibodies, and guidance for management are discussed. Infective, inflammatory and endometrial causes of RPL are discussed in detail. Environmental and lifestyle factors, male factor and unexplained causes are outlined. Levels of evidence and grades of consensus are provided for all evidence-based statements.
PubMed: 38934293
DOI: 10.1111/ajo.13820 -
The Australian & New Zealand Journal of... Jun 2024Guidelines for the investigation and management of recurrent pregnancy loss (RPL) have been developed in Europe, USA and UK, but there is currently no Australasian...
Guidelines for the investigation and management of recurrent pregnancy loss (RPL) have been developed in Europe, USA and UK, but there is currently no Australasian guideline. The Australasian Certificate of Reproductive Endocrinology and Infertility Consensus Expert Panel on Trial Evidence group has prepared a two-part guideline to provide guidance on the management of RPL. In Part I chromosomal, anatomical, and endocrine factors are outlined along with relevant recommendations for clinical management, levels of evidence and grades of consensus. In Part II thrombophilia, autoimmune factors, infective, inflammatory, and endometrial causes, environmental and lifestyle factors, male factor and unexplained causes will be outlined.
PubMed: 38934264
DOI: 10.1111/ajo.13821