Live Birth Rate in Women with Recurrent Pregnancy Loss after In Vitro Fertilization with Concomitant Intravenous Immunoglobulin and Prednisone

Pregnancy loss after in vitro fertilization (IVF) is at least as common as after spontaneous conception. Recurrent pregnancy loss (RPL) may often have an immunological background, and it is therefore relevant to test immune-based interventions in these patients. The objective was to investigate the effect of immunotherapy with intravenous immunoglobulin (IvIg) and prednisone (PRS) as concomitant therapy to IVF in women with RPL after earlier IVF treatments. In a cohort study conducted at The Danish RPL Clinic, 41 women with three or more consecutive pregnancy losses after IVF underwent at least one further IVF cycle with concomitant immunotherapy from 2012 to 2017. The immunotherapy with IvIg and PRS was given before embryo transfer and repeatedly in the first trimester when pregnancy was achieved. Fourteen women (34.2%) achieved a live birth after the first embryo transfer with immunotherapy, and a total of 32/41 (78%) achieved a live birth after up to 4 embryo transfers. Baseline characteristics and the presence of autoantibodies were not significantly different among women achieving live birth or not. The observed 34% birth rate in women with RPL after IVF receiving immunotherapy appears higher than the expected 16–19% birth rate without immunotherapy and is similar to findings in a previous cohort from our clinic. Concomitant immunotherapy as described may be a promising intervention for women with RPL after IVF; however, the effect must be tested in a randomized controlled trial

Chronic endometritis — is it time to clarify diagnostic criteria?

Chronic endometritis is a persistent, low-intensity inflammation of endometrial mucosa, characterized by the infiltration of plasma cells into the endometrial stroma This immunological alteration is thought to be a consequence of a bacterial infection. For a long time, chronic endometritis was poorly investigated and rarely considered in clinical practice because it is either asymptomatic or presents with no specific symptoms. Its association with adverse effects on fertility and retrospectively reported effectiveness of antibiotic treatment were the main reasons for a growing interest in this endometrial pathology. Chronic endometritis is now a hot topic in recurrent pregnancy loss and recurrent implantation failure research. Nevertheless, there are still no recommendations to include chronic endometritis investigation in a clinical evaluation of infertile patients. The uncertain role of this condition is an effect of significant differences in study results presented by different research groups. One important reason for these inconsistent findings is a lack of standardised chronic endometritis diagnostic methods. We present a review of the literature, focusing on the currently available chronic endometritis diagnostic techniques. The review is subdivided into three parts concerning the diagnostic accuracy of three main diagnostic modalities. Histopathological examination of endometrial tissue, hysteroscopic evaluation of uterine cavity and identification of the bacterial factor. In conclusion, it is of great importance to establish a consensus on the diagnostic criteria for chronic endometritis. This is the only way to enhance international cooperation and create well-design multicenter studies to evidence the role of this endometrial pathology in infertility

Smoking during pregnancy reduces vitamin D levels in a Finnish birth register cohort

Objective Maternal vitamin D level in pregnancy may have implications for both the mother and fetus. Deficiency of vitamin D has been linked to several pregnancy complications and fetal skeletal health. Smoking has been associated with reduced serum level of the vitamin D metabolite, 25-hydroxyvitamin D (25(OH)D). Design A nested case-control study within the Finnish Maternity Cohort, a population-based cohort which includes first-trimester sera from 98 % of pregnancies in Finland since 1987. The selection consisted of women with uncomplicated pregnancies. We studied serum concentration of 25(OH)D in 313 non-smoking and forty-six self-reported smoking pregnant women. Setting We hypothesize that pregnant smokers may have an increased risk of low 25(OH)D levels especially during winter months. Participants A control group from an unpublished pregnancy complication study consisting of 359 uncomplicated pregnancies. Individuals who reported that they do not smoke were considered 'non-smokers' (n 313) and those who reported continued smoking after the first trimester of pregnancy were considered 'smokers' (n 46). Results Smokers had significantly lower levels of 25(OH)D irrespective of sampling time (PPeer reviewe

Comparison of a 'freeze-all' strategy including GnRH agonist trigger versus a 'fresh transfer' strategy including hCG trigger in assisted reproductive technology (ART):a study protocol for a randomised controlled trial

Introduction Pregnancy rates after frozen embryo transfer (FET) have improved in recent years and are now approaching or even exceeding those obtained after fresh embryo transfer. This is partly due to improved laboratory techniques, but may also be caused by a more physiological hormonal and endometrial environment in FET cycles. Furthermore, the risk of ovarian hyperstimulation syndrome is practically eliminated in segmentation cycles followed by FET and the use of natural cycles in FETs may be beneficial for the postimplantational conditions of fetal development. However, a freeze-all strategy is not yet implemented as standard care due to limitations of large randomised trials showing a benefit of such a strategy. Thus, there is a need to test the concept against standard care in a randomised controlled design. This study aims to compare ongoing pregnancy and live birth rates between a freeze-all strategy with gonadotropin-releasing hormone (GnRH) agonist triggering versus human chorionic gonadotropin (hCG) trigger and fresh embryo transfer in a multicentre randomised controlled trial. Methods and analysis Multicentre randomised, controlled, double-blinded trial of women undergoing assisted reproductive technology treatment including 424 normo-ovulatory women aged 18-39 years from Denmark and Sweden. Participants will be randomised (1:1) to either (1) GnRH agonist trigger and single vitrified-warmed blastocyst transfer in a subsequent hCG triggered natural menstrual cycle or (2) hCG trigger and single blastocyst transfer in the fresh (stimulated) cycle. The primary endpoint is to compare ongoing pregnancy rates per randomised patient in the two treatment groups after the first single blastocyst transfer. Ethics and dissemination The study will be performed in accordance with the ethical principles in the Helsinki Declaration. The study is approved by the Scientific Ethical Committees in Denmark and Sweden. The results of the study will be publically disseminated. Trial registration number NCT02746562; Pre-results

The reproductive microbiome – clinical practice recommendations for fertility specialists

The interest in and understanding of the human microbiome has grown remarkably over recent years. Advances in molecular techniques have allowed researchers to identify and study the microbiota and also use this information to develop therapeutic solutions for a spectrum of conditions. Alongside the growing interest in the microbiome, societal changes have resulted in many couples looking to start families later in life, therefore increasing the demand for as