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European Society of Human Reproduction and Embryology 2020 HIGHLIGHTS OF THE ANNUAL MEETING OF THE EUROPEAN SOCIETY OF HUMAN REPRODUCTION AND EMBRYOLOGY Virtual Congress, 5th-8th July 2020 The purpose of this report is to capture highlights from the ESHRE 2020 congress. The REPROFACTS faculty has selected the studies presented in this report; putting study findings in perspective and extracting the practice points. The faculty members were independent in their choice of studies and their evaluation and this report is based on the REPROFACTS 2020 Post-ESHRE meeting. The development of this congress report has been financially supported by MERCK KGaA, however MERCK KGaA had no influence on the content and scientific opinions presented in the congress report do not necessarily represent the position of MERCK KGaA. MERCK KGaA is not responsible for the content of the report. Consequently, MERCK KGaA does not give any warranty, express or implied, regarding the scientific use of this report, or regarding any other particular use for any purpose, and MERCK KGaA therefore is not liable for any direct, indirect, incidental, or consequential damages related to the use of the information contained herein. GL-NONF-00570 August 2020 Sponsored by INTRODUCTION TO REPROFACTS Foreword The year 2020 marks a new era in many fields of life and profession, and this is also true for reproductive medicine. For the first time since the inaugural meeting in Bonn in 1985, ESHREs annual get-to-together went exclusively virtual, providing a totally new experience for everyone involved, from presenter to audience to industry. While online lectures on-demand and ease of access to the presentations were convenient (and will likely stay), the inspiration gained from personal contact and the focus to the conference without distraction from routine business at home was certainly missed by many of the 12,520 online participants. The COVID-19 crisis did, however, not impact the quantity or quality of the main scientific program, with 200+ peer-reviewed oral communications and more than 60 invited lectures. The wealth and breadth of information was as challenging as ever, so our REPROFACTs expert team once again shared the subspecialties among each other, sorted out ‘the wheat from the chaff’, and presented the essence of the ESHRE lectures in a one-day meeting in Mainz, Germany, on July 17, 2020. This years REPROFACTS meeting marked the 10th anniversary of an initiative which started as a small ‘POST-ESHRE’ discussion forum and which grew, with Merck as a strong partner, into one of the largest reproductive medicine conferences within the German speaking countries. The COVID crisis also left its mark on the format of REPROFACTS, which was for the first time held as a hybrid-meeting, with online live streaming of the real event. This report contains some of the key highlights from the REPROFACTS meeting 2020. Selection of topics was done by the REPROFACTS faculty, independently and neutrally, with a focus on clinically relevant novelties. Watch Prof. Griesinger discuss the virtual ESHRE 2020 congress. 1 INTRODUCTION TO REPROFACTS Faculty members Prof. Dr. med. habil. Dr. rer. nat. Jens Hirchenhain Jürgen M. Weiss Düsseldorf. Subspeciality: clinical Lucerne. Subspecialities: female infertility embryology and ovarian stimulation Prof. Dr. med. Heribert Kentenich Prof. med. Ludwig Wildt Berlin. Subspecialities: safety and quality, Innsbruck. Subspeciality: endocrinology law and ethics, psychology Priv.-Doz. Dr. rer. nat. Verena Prof. Dr. med. Michael von Wolff Nordhoff Münster. Subspecialities: basic science Bern. Subspecialities: fertility preservation, and reproductive genetics ovarian reserve, surgery Dr. med. Maren Goeckenjan Prof. Dr. med. Michael Zitzmann Dresden. Subspecialities: endometrium, Münster. Subspeciality: andrology endometriosis, early pregnancy 2 CONTENTS Andrology Low male testosterone 5 Negative impact of elevated DFI and HPV presence in sperm 7 Reproductive endocrinology Efficacy and safety of linzagolix on HMB due to uterine fibroids 8 Relugolix for heavy menstrual bleeding due to uterine fibroids 10 Use of testosterone gel treatment in poor ovarian reserve in IVF-ICSI cycles 11 Early pregnancy Pre-treatment with mifepristone to misoprostol in early pregnancy failure 13 Conception after early IVF pregnancy loss - should we wait? 15 Updated terminology for early pregnancy assessment 17 Fertility preservation and reproductive surgery Live birth rate and utilization rate of eggs and embryos following FP 19 LH preserves the meiotic potential of oocytes exposed to chemotherapy 21 Septum resection versus expectant management in women with a septate uterus 22 3 CONTENTS Clinical embryology New evidence on mosaic developmental potential 24 Complex mosaic embryos after preimplantation genetic testing 26 Novel technologies for single-sperm vitrification 27 Intracytoplasmic sperm injection vs conventional IVF in couples with non-male factor infertility 29 Embryos excluding multinucleated cells during blastocyst formation increase their reproductive potential 31 Ovarian stimulation Optimal GnRH antagonist protocol during ovarian stimulation 33 Comparing different progestin regimens for pituitary suppression 34 MPA as a pituitary suppressor instead of a GnRH antagonist during ovarian stimulation 36 Pituitary suppression is not necessary for blocking LH surge during luteal-phase stimulation 37 Natural cycle frozen-thawed embryo transfer 38 Safety & Outcomes Nordic sibling study 39 Imprinting disorders in children born after ART 41 Major congenital malformations risk in children conceived after ICSI 43 Artificially prepared frozen cycles and increased risk of preeclampsia 44 Additional Video Highlights 46 4 Low male testosterone results in a substantial decrease of ANDROLOGY fresh live birth rates in couples with non-male factor infertility undergoing IVF, O-016 P. Drakopoulos et al. Background Sperm production is regulated via a complex and dynamic process that requires interaction of multiple hormones and testicular cell types. Testosterone is indispensable for sperm production; however, testosterone exerts it spermatogenetic action only within a network of endocrine and paracrine signals and tightly coordinated gene and protein expression programs within the testis. Little attention has so far been paid on the potential association of testosterone synthesis with fertility in case of normal sperm parameters. The necessity of routinely evaluating Watch Prof. Michael Zitzmann discuss the potential role of serum testosterone levels in male partner of testosterone as a functional marker for reduced fertility couples trying to conceive is also under dispute. potential. Study In a retrospective analysis (time period 2011 to No relevant difference in sperm parameters were 2018), conducted at the University of Brussels found in patients with low vs. normal testosterone Reproductive Medicine Center, 1,026 couples levels. However, the live birth rate was significantly undergoing a first IVF cycle for non-male factor reduced in the low testosterone group (13%; 95% subfertility were identified. Treatment course and CI, 8, 20) vs. normal testosterone group (23%; outcome of 136 couples (13.3%) with a male 95% CI, 21, 26). This finding remained after partner with a total serum testosterone of <264ng/ adjusting for male and female age, male smoking, dl (<9.2 nmol/L) were compared with couples with female BMI, number of oocytes and embryos, male partners above this threshold. This threshold cause of infertility and SHBG levels (adjusted OR, represents the recommended lower limit of the 0.35; 95% CI, 0.15, 0.79). Accordingly, both total normal total testosterone (TT) in healthy non- and free testosterone in serum were positively obese young men1. In a recent post-hoc analysis associated with live birth likelihood. of the AMIGOS RCT2, a decreased odds of live birth was observed in couples with unexplained infertility undergoing ovarian stimulation with letrozole, clomifen or FSH for timed intercourse or IUI, whose male partner was below 264ng/dl total testosterone (adjusted OR, 0.65; 95% CI, 0.38, 1.12). Only morning testosterone samples and men with no exogenous testosterone or other relevant medication were included in the Brussels study. 5 Low male testosterone results in a substantial decrease of fresh live birth rates in couples with non-male factor infertility ANDROLOGY undergoing IVF, O-016 P. Drakopoulos et al. Univariate-analysis: live birth rate by male partner testosterone serum 40.0 30.0 20.0 10.0 Line Birth Rate (%) Birth Line 0.0 Low Testosterone Normal Testosterone (<264 ng/dl) (≥264 ng/dl) Comment This study aimed at validating the post-hoc observation from the AMIGOS trial2 in the setting of IVF. In both studies, male factor (defined by sperm analysis) was excluded. Thus, the findings hint at a qualitative association of the endocrine and reproductive function of the testis. Practice point Testosterone administration is contra-indicated in the context of fertility treatment. Selective estrogen receptor modulators, gonadotropins and aromatase inhibitors can restore serum testosterone levels, however, the consequences of these pharmacological interventions for natural fertility or ART have not yet been fully clarified. 6 Negative impact of elevated DNA fragmentation index (DFI) ANDROLOGY and human Papillomavirus (HPV) presence in sperm on the outcome of intra-uterine insemination (IUI), O-017 C. Depuydt et al. Background Comment Human Papillomavirus (HPV) are sexually This study corroborates the hypothesis
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