A multi-faceted exploration of unmet needs in the continuing improvement and development of fertility care amidst a pandemic.

PURPOSE: The continuous improvement and development of fertility care, internationally, requires ongoing monitoring of current delivery processes and outcomes in clinical practice. This descriptive and exploratory mixed-methods study was conducted in eight countries (Brazil, China, France, Germany, Italy, Mexico, Spain and the United Kingdom) to assess the unmet needs of fertility patients (male and female), and existing challenges, barriers and educational gaps of physicians and laboratory specialists involved in human fertility care during the COVID-19 pandemic. MATERIALS AND METHODS: The study was deployed sequentially in two phases: 1) in-depth 45-minute semi-structured interviews (n=76), transcribed, coded and thematically analysed using an inductive reasoning approach, 2) an online survey (n=303) informed by the findings of the qualitative interviews, face validated by experts in reproductive medicine, and analysed using descriptive and inferential statistical methods. RESULTS: The integrated results of both phases indicated numerous areas of challenges, including: 1) investigating male-related infertility; 2) deciding appropriate treatment for men and selective use of assisted reproductive technology; and 3) maintaining access to high-quality fertility care during a pandemic. CONCLUSIONS: The paper presents a reflective piece on knowledge and skills that warrant ongoing monitoring and improvement amongst reproductive medicine healthcare professionals amidst future pandemics and unanticipated health system disruptions. Moreover, these findings suggest that there is an additional need to better understand the required changes in policies and organizational processes that would facilitate access to andrology services for male infertility and specialized care, as needed.

International Committee for Monitoring Assisted Reproductive Technology world report: assisted reproductive technology, 2015 and 2016.

OBJECTIVE: To report utilization, effectiveness, and safety of assisted reproductive technologies in 2015 and 2016. DESIGN: Retrospective, cross-sectional survey of 3103 assisted reproductive technology clinics in 74 countries in 2015 and 3249 clinics in 79 countries in 2016 that submitted cycle and pregnancy outcome data through national and regional registries. SUBJECTS: Patients undergoing assisted reproductive technology procedures. EXPOSURE: Assisted reproductive technology. MAIN OUTCOME MEASURES: Outcomes on country, regional, and global levels. RESULTS: Reported for 2015: 2,358,239 cycles with 548,652 babies born; for 2016: 2,807,963 cycles with 647,188 babies born. Estimated in 2015, ≥2,683,677 cycles resulted in >675,134 babies; in 2016, ≥3,100,448 cycles resulted in ≥723,026 babies. Reported cycles represent approximately 80% of global utilization. In 2015 and 2016, 27.6% and 27.8%, respectively, of women undergoing fresh autologous cycles were age ≥40 years. Frozen-thawed embryo transfer cycles accounted for 47.0% and 51.9%, respectively, of all embryo transfers in 2015 and 2016. Oocyte donation cycles accounted for 6.7% and 7.1% of all embryo transfers in 2015 and 2016. Intracytoplasmic sperm injection was performed in 57.7% and 56.4% of autologous aspiration cycles in 2015 and 2016, respectively. The cumulative delivery rate per aspiration cycle for fresh and frozen-thawed embryo transfer was 32.4% in 2015 and 33.1% in 2016, respectively. The average number of transferred embryos was 1.70 in 2015 and 1.69 in 2016. The proportion of single embryo transfers in fresh autologous cycles increased from 42.1% in 2015 to 44.0% in 2016. The twin delivery rate decreased from 16.0% in 2015 to 14.7% in 2016, and the triplet rate decreased from 0.6% in 2015 to 0.4% in 2016. The proportion of single embryo transfers in frozen-thawed embryo transfer autologous cycles was 62.2% in 2015 and 64.2% in 2016, with twin and triplet rates of 10.1% and 0.3% in 2015 and 10.0% and 0.2% in 2016, respectively. CONCLUSION: Utilization of assisted reproductive technology and births per cycle increased from 2015 to 2016 while multiple births were reduced . Increasing proportion of frozen-thawed embryo transfer cycles, continuing wide variation in use of intracytoplasmic sperm injection, and increase in single embryo transfer rates are reported.

International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology, 2014†.

STUDY QUESTION: What were the utilization, effectiveness and safety of practices in assisted reproductive technologies (ART) globally in 2014 and what global trends could be observed? SUMMARY ANSWER: The estimated total number of ART cycles conducted in 76 participating countries in 2014 was 1.93 million representing ∼66% of global activity, with 5-year trends including an increase in success rates and proportion of frozen embryo transfer (FET) cycles, improvement in cumulative live birth rates per aspiration, a continued increase in single embryo transfer (SET) and thus a reduction in multiple birth rates, an increase in preimplantation genetic testing and stabilization in the use of intracytoplasmic sperm injection (ICSI). WHAT IS KNOWN ALREADY: ART is widely practiced throughout the world but continues to be characterized by significant disparities in utilization, practice, effectiveness and safety. The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) annual world report series provides an important instrument for tracking trends in ART treatment and for providing clinical and public health data to ART professionals, health authorities, patients and the general public. STUDY DESIGN, SIZE, DURATION: A retrospective, cross-sectional survey on ART procedures performed globally during 2014 was carried out. A new method for calculating ART utilization rates and number of babies born was introduced in this latest ICMART world report. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 76 countries and 2 746 ART centres submitted data through national and regional ART registries on ART cycles performed during 2014 and their treatment and pregnancy outcomes. ART cycles and outcomes are described at a country level, regionally and globally. Aggregate country data are processed and analyzed based on methods developed by ICMART. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1 629 179 ART cycles were reported for the treatment year 2014. After imputing data for missing values and non-reporting centres in reporting countries, an estimated 1 929 905 cycles resulted in >439 039 babies in reporting countries. From 2010 to 2014, the number of reported non-donor aspirations and FET cycles increased by 37.3% and 67.5%, respectively. The proportion of women aged ≥40 years undergoing non-donor ART increased from 23.2% in 2010 to 27.0% in 2014. ICSI, as a percentage of non-donor aspiration cycles, remained relatively stable at 64.8%. The IVF/ICSI combined delivery rates per fresh aspiration and FET cycle were 19.9% and 24.3%, respectively. In fresh non-donor cycles, SET increased from 30.0% in 2010 to 40.0% in 2014, while the average number of transferred embryos decreased from 1.95 to 1.73-but with wide country variation. The rate of twin deliveries following fresh non-donor transfers continued to decrease, from 20.4% in 2010 to 16.2% in 2014, and the triplet rate decreased from 1.1% to 0.5%. In FET non-donor cycles in 2014, the SET rate was 61.6%, with an average of 1.43 embryos transferred, resulting in twin and triplet rates of 10.1% and 0.2%, respectively. The cumulative delivery rate per aspiration increased from 27.1% in 2010 to 32.1% in 2014. The overall perinatal mortality rate per 1 000 births was 19.4 following fresh IVF/ICSI cycles and 9.5 following FET cycles. Among reporting countries, oocyte donation cycles represented 7.3% of all embryo transfers (89 751 transfer cycles) and resulted in 39 278 babies. LIMITATIONS, REASONS FOR CAUTION: The data presented are dependent on the quality and completeness of data submitted by individual countries to ICMART directly or through regional registries. This report covers approximately two-thirds of world ART activity. China is a major contributor of global cycles missing from this report. Continued efforts to improve the quality and consistency of ART data reported by registries are still needed, including the use of internationally agreed standard definitions (The International Glossary of Infertility and Fertility Care). A new method was introduced in this report to calculate ART utilization and number of babies born following ART; therefore, these results are not directly comparable with previous reports. WIDER IMPLICATIONS OF THE FINDINGS: The ICMART world reports provide the most comprehensive global statistical census and review of ART utilization, effectiveness, safety and quality. While ART treatment effectiveness and safety continue to increase globally, the wide disparities in access to treatment, procedures performed and embryo transfer practices warrant attention by clinicians and policymakers. The new method for estimating ART utilization and number of babies born provided more conservative estimates compared to the previuos method. STUDY FUNDING/COMPETING INTEREST(S): ICMART receives unrestricted grants from Abbott and Ferring Pharmaceuticals. ICMART also acknowledges financial support from the following organizations: American Society for Reproductive Medicine; Asia Pacific Initiative on Reproduction; European Society of Human Reproduction and Embryology; Fertility Society of Australia and New Zealand; Japan Society for Reproductive Medicine; Japan Society of Fertilization and Implantation; Red Latinoamericana de Reproducción Asistida; and the Society for Assisted Reproductive Technology. S.D. reports industry sponsorship for attendance of conference from Ferring, and research grants to support African Network and Registry of ART from Ferring and Merck outside the submitted work. F.Z.-H. reports lectures at organized webinars for Ferring and Merck. O.I. reports honoraria for consulting from Ferring, Merck and ObsEva, as well as honoraria for lectures from Ferring and Merck. G.M.C., J.d.M., M.B., M.S.K. and G.D.A. have nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

ESHRE guideline: medically assisted reproduction in patients with a viral infection/disease.

STUDY QUESTION: What is the recommended management for medically assisted reproduction (MAR) in patients with a viral infection or disease, based on the best available evidence in the literature? SUMMARY ANSWER: The ESHRE guideline on MAR in patients with a viral infection/disease makes 78 recommendations on prevention of horizontal and vertical transmission before, during and after MAR, and the impact on its outcomes, and these also include recommendations regarding laboratory safety on the processing and storage of gametes and embryos testing positive for viral infections. WHAT IS KNOWN ALREADY: The development of new and improved anti-viral medications has resulted in improved life expectancy and quality of life for patients with viral infections/diseases. Patients of reproductive age are increasingly exploring their options for family creation. STUDY DESIGN SIZE DURATION: The guideline was developed according to the structured methodology for the development of ESHRE guidelines. After the formulation of nine key questions for six viruses (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human papilloma virus, human T-lymphotropic virus I/II and Zika virus) by a group of experts, literature searches and assessments were performed. Papers published up to 2 November 2020 and written in English were included in the review. Evidence was analyzed by female, male or couple testing positive for the virus. PARTICIPANTS/MATERIALS SETTING METHODS: Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. There were 61 key questions to be answered by the guideline development group (GDG), of which 12 were answered as narrative questions and 49 as PICO (Patient, Intervention, Comparison, Outcome) questions. A stakeholder review was organized after the finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE: This guideline aims to help providers meet a growing demand for guidance on the management of patients with a viral infection/disease presenting in the fertility clinic.The guideline makes 78 recommendations on prevention of viral transmission before and during MAR, and interventions to reduce/avoid vertical transmission to the newborn. Preferred MAR treatments and interventions are described together with the effect of viral infections on outcomes. The GDG formulated 44 evidence-based recommendations-of which 37 were formulated as strong recommendations and 7 as weak-33 good practice points (GPP) and one research only recommendation. Of the evidence-based recommendations, none were supported by high-quality evidence, two by moderate-quality evidence, 15 by low-quality evidence and 27 by very low-quality evidence. To support future research in the field of MAR in patients with a viral infection/disease, a list of research recommendations is provided. LIMITATIONS REASONS FOR CAUTION: Most interventions included are not well-studied in patients with a viral infection/disease. For a large proportion of interventions, evidence was very limited and of very low quality. More evidence is required for these interventions, especially in the field of human papilloma virus (HPV). Such future studies may require the current recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS: The guideline provides clinicians with clear advice on best practice in MAR for patients with a viral infection/disease, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in the field. STUDY FUNDING/COMPETING INTERESTS: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive any financial incentives, all work was provided voluntarily. A.D. reports research fees from Ferring and Merck, consulting fees from Ferring, outside the submitted work. C.P. reports speakers fees from Merck and MSD outside the submitted work. K.T. reports speakers fees from Cooper Surgical and Ferring and consultancy fees as member of the advisory board BioTeam of Ferring, outside the submitted work. The other authors have no conflicts of interest to declare. DISCLAIMER: This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at  www.eshre.eu/guidelines.).

Effects of phytoestrogen extracts isolated from pumpkin seeds on estradiol production and ER/PR expression in breast cancer and trophoblast tumor cells.

Phytoestrogens have a controversial effect on hormone-dependent tumours. Herein, we investigated the effect of the pumpkin seed extract (PSE) on estradiol production and estrogen receptor (ER)-α/ER-ß/progesterone receptor (PR) status on MCF7, Jeg3, and BeWo cells. The PSE was prepared and analyzed by mass spectrometry. MCF7, Jeg3, and BeWo cells were incubated with various concentrations of PSE. Untreated cells served as controls. Supernatants were tested for estradiol production with an ELISA method. Furthermore, the effect of the PSE on ER-α/ER-ß/PR expression was assessed by immunocytochemistry. The PSE was found to contain both lignans and flavones. Estradiol production was elevated in MCF7, BeWo, and Jeg3 cells in a concentration-dependent manner. In MCF7 cells, a significant ER-α downregulation and a significant PR upregulation were observed. The above results after properly designed animal studies could highlight a potential role of pumpkin seed's lignans in breast cancer prevention and/or treatment.

Consultations of HIV-infected women who wish to become pregnant.

PURPOSE: The aim of this study was to determine the impact and outcome of consultations of HIV-infected women if a pregnancy is planned. METHODS: This study was performed retrospectively based on patient's records of HIV-infected women with the desire to become pregnant between 2000 and 2008. Relevant data regarding HIV infection, obstetrical history, diagnostic procedures and medical interventions related to conception, as well as pregnancy outcomes, were evaluated. RESULTS: A total of 57 HIV-infected women (and their partner) were included; 38% (n = 22) of the couples showed a reduced fertility and 24 women (42%) became pregnant once or several times during the study period. Conception resulted from unprotected intercourse (n = 11), self-insemination (n = 10), assisted insemination (n = 2) or in vitro fertilization (n = 1). The outcome of all pregnancies was: 26 live births, 1 intrauterine fetal demise (38 weeks), 1 miscarriage, 1 cervical pregnancy and 1 legal abortion. No horizontal transmission occurred in serodiscordant couples. Seven (12%) women were lost to follow-up, 12 couples (21%) abandoned the attempt to get pregnant, and 14 couples (25%) reported an ongoing wish for a child. CONCLUSIONS: In this group of HIV-affected couples, we showed a high rate of reduced fertility. In our study, consultations and interventions led to a pregnancy rate of 42% without horizontal transmission of HIV.

Screening for Chlamydia trachomatis in pregnancy: a retrospective analysis in a German urban area.

OBJECTIVE: Chlamydia trachomatis infection is the most common bacterial sexual transmitted disease. Nearly 75% of all cases appear clinically unapparent and can cause, especially when getting chronically, infertility. Regarding pregnancy, a nationwide screening for C. trachomatis was established since April 1995. The aim of this study was to determine the percentage of tested patients throughout these 7 years to evaluate the execution of the German guidelines. MATERIALS AND METHODS: Between 2001 and 2007, 12,865 patients were evaluated retrospectively concerning a Chlamydia trachomatis testing. RESULTS: A test was performed for chlamydial infection in 10,088 patients (78.4%). 65 pregnant patients (0.5%) out of 1,008 tested patients were positive for Chlamydia trachomatis. The part of tested patients was rising significantly from 2001 to 2007. In 2001, 68.3% pregnant patients were tested. The number of screened patients increased continuously up to 85.2% in 2007 (p < 0.001). The percentage of positive tested patients ranged from 0.27% in 2003 to 0.74% in 2005 (mean 0.50%). CONCLUSION: Since 1995, a screening for Chlamydia trachomatis has to be offered to every pregnant woman according to the German guidelines. The number of tested pregnant patients was rising from 68.3 to 85.2% within the evaluated 7 years, which would be a necessary and welcome trend. Interestingly, the mean prevalence of 0.5% of positive tested patients in this analysed urban population seems to be very low. An explanation might be the usage of the point-of-care (POC) tests and its low sensitivity. Testing by nucleic acid amplification might lead to a higher detection rate. Although the awareness concerning Chlamydia trachomatis testing during pregnancy seems to have been changed over the recent years, these data are still dissatisfactory.

Fertility preservation in >1,000 patients: patient's characteristics, spectrum, efficacy and risks of applied preservation techniques.

INTRODUCTION: Data on the characteristics of female patients counselled for fertility preservation and the efficacy and risk of the applied procedures are still poor. We therefore analysed the registry of a network of 70 infertility centers which are involved in fertility preservation in Germany, Switzerland and Austria, called FertiPROTEKT ( hhtp://www.fertiprotekt.eu ). MATERIALS AND METHODS: 1,280 counselled patients (15-40 years) were analysed regarding characteristics and different fertility preservation treatments before cytotoxic therapy in 2007-2009. RESULTS: 34.8% of the counselled patients were diagnosed with breast cancer, 30.5% with Hodgkin's lymphoma, 25.4% with other malignancies and 9.3% with non-malignant diseases. 89.6% of the treated breast cancer patients were 25-40 years of age, and 87.5% of the lymphoma patients were 15-30 years of age. At the time of counselling, 85.3% of the breast cancer patients and 92.7% of the lymphoma patients were childless. 1,080 patients received a single or combined therapy such as GnRH agonists (n = 823), cryopreservation of ovarian tissue (n = 500), ovarian stimulation (n = 221) and transposition of the ovaries (n = 24). Only one severe complication, requiring postponement of the chemotherapy, was documented. In stimulated patients, 2,417 oocytes (mean n = 11.6, SD ± 7.7) were received. Fertilisation rate per received oocyte was 61.3%. CONCLUSIONS: Fertility preservation programmes mainly involve women without children, diagnosed with breast cancer or Hodgkin's lymphoma. Fertility preservation techniques can be applied with low risk. The limited and age-dependant success rate of the different therapies require individualised approaches of single or combined fertility preservation techniques.

Impact of female and male obesity on IVF/ICSI: results of 700,000 ART-cycles in Germany.

To our knowledge, this is the first analysis in which male and female weights have been combined. The registry dataset covering a 12-year period was analysed for all treatment cycles where an embryo transfer was reported. In all, 706,360 cycles were analysed. Treatments include IVF, ICSI, IVF/ICSI and CPE. The highest success rate in IVF cycles was found in couples, with an obese male partner. In the group of obese women, the pregnancy rate decreased to 27.2%. Similar to IVF treatment, the highest success rate in ICSI cycles was found in couples, where either the male or the female partner was obese. The highest success rate in cycles with a cryopreserved embryo transfer was observed in couples where both partner were obese. The lowest success rate was seen where the female partner was obese. Our data analysis suggests that the combination of an obese male and a normal-weight female is positively related to better implantation rates in IVF as well as ICSI-cycles. This combination is more likely to be found in couples with a higher social status. Therefore, the increased pregnancy rate in this group might as well be related to other lifestyle factors associated with higher social status.

Evidence of inhibin/activin subunit betaC and betaE synthesis in normal human endometrial tissue.

BACKGROUND: Inhibins are important regulators of the female reproductive system. Recently, two new inhibin subunits betaC and betaE have been described, although it is unclear if they are synthesized in normal human endometrium. METHODS: Samples of human endometrium were obtained from 82 premenopausal, non-pregnant patients undergoing gynecological surgery for benign diseases. Endometrium samples were classified according to anamnestic and histological dating into proliferative (day 1-14, n = 46), early secretory (day 15-22, n = 18) and late secretory phase (day 23-28, n = 18). Immunohistochemical analyses were performed with specific antibodies against inhibin alpha (n = 81) as well as inhibin betaA (n = 82), betaB (n = 82), betaC (n = 74) and betaE (n = 76) subunits. RT-PCR was performed for all inhibin subunits. Correlation was assessed with the Spearman factor to assess the relationship of inhibin-subunits expression within the different endometrial samples. RESULTS: The novel inhibin betaC and betaE subunits were found in normal human endometrium by immunohistochemical and molecular techniques. Inhibin alpha, betaA, betaB and betaE subunits showed a circadian expression pattern, being more abundant during the late secretory phase than during the proliferative phase. Additionally, a significant correlation between inhibin alpha and all inhibin beta subunits was observed. CONCLUSIONS: The differential expression pattern of the betaC- and betaE-subunits in normal human endometrial tissue suggests that they function in endometrial maturation and blastocyst implantation. However, the precise role of these novel inhibin/activin subunits in human endometrium is unclear and warrants further investigation.

The human endometrium expresses the glycoprotein mucin-1 and shows positive correlation for Thomsen-Friedenreich epitope expression and galectin-1 binding.

Mucin 1 (MUC1) is a glycoprotein in human endometrium and is abundant at the luminal epithelial surface in the receptive phase. It has a highly glycosylated ecto-domain that contains keratan sulfate chains, that disappears at the time of implantation. In addition, the glycoforms on MUC1 differ in fertile and infertile women. Therefore the aims of this study were investigations on glycosylation of MUC1 with the Thomsen-Friedenreich (TF) epitope on normal human endometrium throughout the menstrual cycle and binding of galectin-1 on the TF epitope in the endometrium and the expression of galectin-1 on the human oocyte. Human endometrial tissue was obtained from 54 premenopausal patients and was immunohistochemically analyzed with monoclonal antibodies against MUC1, TF epitope, galectin-1, and biotinylated galectin-1. In addition, human oocytes were analyzed for TF, galectin-1 expression, and galectin-1 binding. We identified a significant upregulation of MUC1 and TF epitope and, in addition, galectin-1 binding in glandular epithelium and epithelial apical surface tissue from proliferative to secretory phase. With double staining experiments, we identified a coexpression of TF and MUC1 in the early secretory phase and galectin-1 binding to TF during the same period of time. In addition we identified TF epitope and galectin-1 expression plus binding on the human oocyte and irregularly fertilized oocytes. Upregulation of TF epitope on the glandular epithelium and epithelial apical surface tissue in the secretory phase and binding of galectin-1 at the same time show the possibility of galectin-1-mediated trophectoderm binding to the endometrium within the window of implantation.

[Typical causes of infertility: what diagnostic measures can the general practitioner take?]. / Typische Ursachen der Infertilität. Was kann der Praktiker diagnostisch tun?

At the latest after one year of their trying to achieve a pregnancy, a couple should seek medical advice. In many cases, the case history alone will provide important relevant information. Initial helpful measures include the utilization of the optimal time for conception, and an ultrasonographic follicle count. In addition to endocrinological tests in the woman, an androgenic work-up should be performed at an early stage and, where applicable, further diagnostic steps undertaken.

Expression of the inhibin/activin subunits (-alpha, -betaA and -betaB) in normal and carcinogenic endometrial tissue: possible immunohistochemical differentiation markers.

Inhibins (INH) are dimeric glycoproteins, composed of an alpha-subunit (INH-alpha) and one of two possible beta-subunits (INH-betaA or -betaB), with substantial roles in human reproduction and in endocrine-responsive tumors. The aims of this study were to determine the frequency and tissue distribution of INH-alpha, -betaA and -betaB in normal and malignant endometria. Samples were obtained from normal (n=46), atrophic (n=8) and endometrioid carcinoma tissue (EC; G1=93; G2=32; G3=14). INH-alpha was significantly higher in normal compared to malignant endometrial tissue, showing a cyclical variation throughout the menstrual cycle. EC G3 did not express this subunit. INH-betaA and -betaB showed specific staining reactions within the tumor cells. The highest intensity of INH-betaA was observed in the normal secretory phase compared to adenocarcinomas (p<0.05). For INH-betaB, the significantly highest expression was noted in EC G3 compared to EC G2 (p<0.05) and atrophic endometrial tissue. In conclusion, INH-alpha, -betaA and -betaB were immunolabeled in normal and malignant endometria. INH-alpha was expressed in a declining relationship in the transition from normal to tumor tissue, suggesting a tumor suppressive function in EC. A high expression of INH-betaB was observed in EC G3 compared to G2, suggesting an important role in the progression of endometrial carcinogenesis. However, the utilization of these subunits as specific tumor markers still remains unclear.

Glycodelin A is expressed differentially in normal human endometrial tissue throughout the menstrual cycle as assessed by immunohistochemistry and in situ hybridization.

OBJECTIVE: To [1] evaluate glycodelin A immunolabeling in normal endometrium with specific monoclonal (mAb) and polyclonal peptide (pAb) antibodies, [2] to assess glycodelin messenger RNA (mRNA) by in situ hybridization, and [3] to conduct deglycosylation experiments to evaluate the recognized epitope of the mAb vs. pAb. DESIGN: Retrospective immunohistochemical analysis. SETTING: University institute and hospital in Germany. PATIENT(S): Normal human endometrial tissue from the proliferative (PP), early secretory, and late secretory phases were obtained from patients undergoing surgery for benign diseases. INTERVENTION(S): Generation of a pAb in rabbit, immunohistochemistry, and in situ hybridization. MAIN OUTCOME MEASURE(S): Semiquantitative and computerized analysis. RESULT(S): A statistically significant increase of the glycodelin A immunolabeling in the late secretory phase compared with PP was demonstrated by using the mAb. Polyclonal-peptide antibody immunolabeling also showed a rise between the PP and late secretory phases, but without statistical significance. In situ hybridization demonstrated a statistically significantly higher mRNA content during the early secretory phase compared with during PP. CONCLUSION(S): Glycodelin was demonstrated in normal endometrium at the protein and mRNA levels. The mAb may be more useful in assessing glycodelin expression in endometrium, because it probably can bind to glycodelin A-unique glycan structures, in contrast to the peptide pAb. This is of major interest because it may reveal possible structural and functional relationships in different parts of this molecule and elucidate possible functions of this glycoprotein in human endometrial tissue.

Inhibin/activin subunits alpha, beta-A and beta-B are differentially expressed in normal human endometrium throughout the menstrual cycle.

Inhibins are dimeric glycoproteins composed of an alpha (alpha) subunit and one of two possible beta (beta-) subunits (betaA or betaB). The aims of this study were to assess the frequency and tissue distribution patterns of the inhibin subunits in normal human endometrium. Samples from human endometrium from proliferative phase (PP; n=32), early secretory phase (ES; n=10) and late secretory phase (LS; n=12) were obtained. Immunohistochemistry, immunofluorescence and a statistical analysis were performed. All three inhibin subunits were expressed by normal endometrium by immunohistochemistry and immunofluorescence. Inhibin-alpha was primarily detected in glandular epithelial cells, while inhibin-beta subunits were additionally localised in stromal tissue. Inhibin-alpha staining reaction increased significantly between PP and ES (P<0.05), PP and LS (P<0.01), and ES and LS (P<0.02). Inhibin-betaA and -betaB were significant higher in LS than PP (P<0.05) and LS than ES (P<0.05). All three inhibin subunits were expressed by human endometrium varying across the menstrual cycle. This suggests substantial functions in human implantation of inhibin-alpha subunit, while stromal expression of the beta subunits could be important in the paracrine signalling for adequate endometrial maturation. The distinct expression in human endometrial tissue suggests a synthesis of inhibins into the lumen and a predominant secretion of activins into the stroma.

Stress relief after infertility treatment--spontaneous conception, adoption and psychological counselling.

OBJECTIVE: In this study, we sought to evaluate characteristics of couples with spontaneous conceptions after treatment with assisted reproductive technologies (ART). STUDY DESIGN: Data from 254 couples who underwent 1127 therapy cycles between November 1987 and February 1997, were analyzed. Chi-Square (chi(2)) test and Student's t-test were used. P<0.05 was considered significant. RESULTS: Spontaneous pregnancies occurred in 14% of all treated couples. Psychological counselling only was performed in 21% but was observed significantly more frequently among patients without later spontaneous conception. Ten percent of all treated couples applied for adoption. The miscarriage rate was significantly higher in the group of treatment dependent pregnancies compared to the group of patients with later spontaneous conception (27% versus 9%). The spontaneous conception rate differed significantly depending on women's age and normal semen analysis. CONCLUSION: Appearance of spontaneous conception after ART-procedures should be taken into account in the first patient's interview. Depending on women's age and andrological parameters, treatment-success will differ. The positive impact of psychological counselling for stress relief during and after therapy should also be noted, even though a statistically significant impact could not be demonstrated in the present study. Adoption should be discussed as an alternative to overcome infertility.

Impact of reproductive history on in vitro fertilization and intracytoplasmic sperm injection outcome: evidence from the German IVF Registry.

OBJECTIVE: To evaluate the effect of reproductive history on the outcome of different procedures in assisted reproductive technologies (ART) comparing IVF, ICSI, and cryopreserved embryo transfer (CPE). DESIGN: Prospective registration of ART cycles and their outcomes. SETTING: One hundred three reproductive programs in Germany. PATIENT(S): Women undergoing 174,909 ART procedures from January 1998 through December 2000. INTERVENTION(S): Data analysis of reproductive history collected by the German IVF Registry; multiple logistic regression modeling of success rates. MAIN OUTCOME MEASURE(S): Effect of type of conception and outcome of previous pregnancies, duration of infertility, female's age, and type of ART on clinical pregnancy rate per retrieval. Odds ratios with 95% CIs are reported. RESULT(S): More than one previous pregnancy was negatively correlated with outcome of IVF, ICSI, or CPE. This association disappeared when female age was restricted to a maximum of 35 years. A previous pregnancy achieved by spontaneous conception had less impact on outcome of IVF, ICSI or CPE outcome than did a previous assisted conception. Previous live births and miscarriages demonstrated a statistically significant increase compared with ectopic pregnancies and induced abortions. CONCLUSION(S): Reproductive history must be considered when counseling subfertile couples. Female age, method of conception, and previous pregnancy outcome have a significant effect on IVF, ICSI, and CPE outcome.