Early pregnancy complications after frozen-thawed embryo transfer in different cycle regimens: A retrospective cohort study.

OBJECTIVE Frozen-thawed embryo transfers (FET) are a key component of assisted reproductive technologies (ART) and various cycle regimens are used worldwide because of insufficient evidence to favour particular transfer schedules. In this study, we investigated the associations between different cycle regimens and early pregnancy complications as well as live birth rates (LBR) per pregnancy after FET. STUDY DESIGN We conducted a retrospective cohort study analysing a total of 7342 pregnancies after FET registered in the Swiss IVF Registry from 2014 to 2019. Women were divided into three groups according to the different cycle regimens: Natural Cycles (NC-FET, n = 998), low-dose Stimulation Cycles (SC-FET, n = 984) and Hormone Replacement Cycles (HRC-FET, n = 5360) leading to pregnancy. Outcomes included early pregnancy complications such as bleeding, miscarriages and ectopic pregnancies. Additionally, we evaluated LBR per pregnancy. Incidences were compared using Fisher's exact or Chi-square tests. Mean values were compared using t-tests. Multivariate mixed model analysis was performed with early pregnancy complications as outcome. RESULTS The incidence of bleeding in the first trimester (NC: 3.5 %, SC: 4.3 %, HRC: 8.4 %; p < 0.001) and miscarriage < 12 weeks (NC: 19.0 %, SC: 19.7 %, HRC: 29.1 %; p < 0.001) was highest in HRC-FET. Multivariate analysis revealed almost doubled adjusted odds ratios of bleeding in the first trimester (aOR 1.92; 95 % CI 1.30-2.81) and miscarriage < 12 weeks (aOR 1.82; 95 % CI 1.51-2.19) in HRC-FET vs NC-FET. There were comparable odds ratios in HRC-FET vs SC-FET. No differences were observed in the outcomes between SC-FET and NC-FET. Highest proportion of LBR per pregnancy (NC: 78.0 %, SC: 77.2 %, HRC: 68.2 %%; p < 0.001) was reported in NC-FET. CONCLUSIONS This is the latest large European register study evaluating early pregnancy complications and LBR per pregnancy after FET between all three different cycle regimens. Miscarriage rate was highest in HRC-FET which can be translated into lower LBR. Therefore, HRC-FET should be avoided and replaced by SC-FET or NC-FET to achieve better pregnancy outcomes

The role of Natural Cycle IVF in assisted reproduction.

Natural Cycle IVF (NC-IVF) with and without modifications is being increasingly performed. NC-IVF and conventional gonadotropin-stimulated IVF (cIVF) should not be understood as competing treatments, but as complementary treatments with different target groups and to some extent other indications. NC-IVF is particularly interesting for couples who wish to save money, wish a treatment with as few risks as possible and for women who would like to avoid selection and cryopreservation of embryos. NC-IVF therefore contributes to the concept of individualized and patient-oriented therapy. The time to pregnancy is slightly longer than with conventional IVF. NC-IVF is particularly suitable for younger women and for women with a very low ovarian reserve. In this article, the principles of NC-IVF, i.e. monofollicular IVF without gonadotropin stimulation, are described and the technical differences to cIVF, advantages and disadvantages, perinatal outcome and indications for NC-IVF are highlightened

GnRH analogs do not protect ovaries from chemotherapy-induced ultrastructural injury in Hodgkin's lymphoma patients

Purpose: To determine the protective effect of gonadotropin-releasing hormone analogs (GnRHa) using several ultrasound and endocrine markers to detect ultrastructural ovarian damage in Hodgkin's lymphoma patients. Methods: Ten patients who had been treated for Hodgkin's lymphoma and had received GnRHa to protect ovarian function were matched with patients at similar age, who had received the same chemotherapy regimens without GnRHa. In addition, ten healthy women at the same age were matched to the study groups to compare ovarian markers. Blood samples were drawn to determine anti-Müllerian hormone, Inhibin B, follicle-stimulating hormone and transvaginal ultrasound scans were performed to determine antral follicle count and ovarian volume. All women were asked about their menstrual cycle pattern. Results: No difference was found when comparing the ovarian parameters of both study groups. Compared with healthy women, all ovarian parameters in the Hodgkin's lymphoma patients were significantly different. Conclusions: The results of this study demonstrate ultrastructural ovarian damage in Hodgkin's lymphoma patients irrespective of GnRHa co-treatment. These findings do not support previous studies, showing GnRHa to protect ovarian functio

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 (15-40years) 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 25-40years of age, and 87.5% of the lymphoma patients were 15-30years 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 technique

Awareness of non-communicable diseases in women: a cross-sectional study.

Chronic non-communicable diseases (NCD) are the major reason for death, morbidity, loss of independency and public health cost. NCD prevalence could be significantly reduced by adopting a healthy lifestyle. This cross-sectional cohort study (online survey) in 221 women aimed to assess NCD awareness, knowledge about NCD prevention and willingness to adopt a healthier lifestyle in women. Overall, NCD awareness level was quite high with, however, information mainly originating from lay media, probably being one reason for false estimations of age groups mainly affected by NCD, impact of NCD on quality of life, NCD mortalities, and the extent of NCD prevention by lifestyle interventions, respectively. Furthermore, also due to mainly lay media, half of women knew online NCD risk calculators, most of them would like to know their NCD risk, but only few had been offered NCD risk calculation by their physician. The mean threshold for willing to adopt a healthier lifestyle was a roughly calculated 37% 5-10 years risk to develop a certain NCD. Acceptance of non-pharmacological interventions for NCD prevention was high, however, major barriers for not implementing a healthier lifestyle were lack of expert information and lack of time. In conclusion, future public health strategies should focus on distributing better understandable and correct information about NCD as well as meeting the individuals' request for personalized NCD risk calculation. Furthermore, physicians should be better trained for personalized NCD prevention counseling

Current Perspectives on Research Ethics in Qualitative Research

In this article, we provide a brief introduction to the special issue on research ethics in qualitative research. We describe the general context within which our idea emerged to organize a special issue and present its design and, for purposes of transparency, some particulars with respect to the selection and review process. We sketch some of the common themes that are shared across parts of the paper set, including critical analysis of ethics codes and ethics reviews, the intricacies of informed consent, confidentiality and anonymity in qualitative research and questions of vulnerability

High dose gonadotropin stimulation increases endometrial thickness but this gonadotropin induced thickening does not have an effect on implantation.

INTRODUCTION Endometrial thickness <8mm is related with lower pregnancy rates. This raises the question if endometrial thickness can be increased by gonadotropin stimulation to increase estradiol (E2) concentration and if such an artificial thickening of the endometrium has an effect on implantation. A model to address this question is the comparison of endometrial thickness and outcome parameters in conventional gonadotropin stimulated IVF (cIVF) compared to unstimulated natural cycle IVF (NC-IVF). MATERIAL AND METHODS Retrospective study including 235 cIVF and 616 NC-IVF cycles without embryo selection and with fresh transfer on day 2 and 3 from 2015 to 2019. Endometrial and E2 measurements were included and analysed between day -4 and -2 (0 = day of aspiration). The effects of E2 on endometrial thickness, endometrial growth and the effect of endometrial thickness on implantation rates and live births were analysed. RESULTS Endometrial thickness was found to be higher in cIVF compared to NC-IVF (p < 0.001). On day -2, the day when ovulation was triggered, mean endometrial thickness was 9.75 ± 2.05mm and 8.12 ± 1.66mm, respectively. The increase in endometrial thickness slowed down with increasing E2 concentrations (time x estradiol concentration: -0.19, p = 0.010). Implantation rates were not significantly different in cIVF and NC-IVF cycles (clinical pregnancy rate: 19.1% vs. 15.4% p = 0.2; live birth rate: 12.8% vs. 11.7%, p = 0.8). CONCLUSIONS Endometrial growth dynamic is different and endometrium is thicker in cIVF compared to NC-IVF. Pregnancy and live birth rates are not different. Gonadotropin induced thickening of the endometrium does not appear to improve implantation

Gonadotropin Stimulation Reduces the Implantation and Live Birth Rate but Not the Miscarriage Rate of Embryos Transferred When Compared to Unstimulated In Vitro Fertilization.

Research suggests that gonadotropin stimulation in in vitro fertilization (IVF) treatment affects embryo quality and the endometrium that might influence embryo implantation, placentation and establishment of a viable pregnancy. We assessed the impact of gonadotropin stimulation on implantation, live birth and miscarriage rates per transferred embryo by comparing stimulated and unstimulated IVF treatment. In a cohort of 728 couples, 1310 IVF cycles with successful embryo transfer were analysed; 857 cycles were stimulated with gonadotropins > 75 IU/day (333 poor responder < 4 oocytes; 524 normal responders), and 453 were unstimulated. In total, 1913 fresh cleavage-stage embryos were transferred. Zygote but no embryo selection was performed, and supernumerous zygotes were vitrified. The implantation rate was defined as number of sonographically detected amniotic sacs; live birth rate as number of children born per transferred embryo. Modified mixed effect Poisson regression was used to account for the dependency of cycles and embryos within the same women and the same transfer cycle. Adjustments were made for maternal age, parity, primary or secondary infertility and indication for IVF. Per transferred embryo, implantation rates (rate ratio (RR) 1.37; 95% CI 1.04-1.81; p = 0.028; aRR 1.42; 95% CI 1.10-1.84; p = 0.008) and live birth rates (RR 1.33; 95% CI 0.95-1.86; p = 0.093; aRR 1.38; 95% CI 1.01-1.88; p = 0.044) were higher in NC-IVF compared to cIVF normal responders. Miscarriage did not differ (RR 0.99; 95% CI 0.59-1.65; p = 0.965; aRR 0.90; 95% CI 0.52-1.53 p = 0.698). Similar results were obtained in poor responders. The study suggests an impact of gonadotropin stimulation on the implantation potential of embryos