Human implantation: The complex interplay between endometrial receptivity, inflammation, and the microbiome.

Human embryo implantation is an intricate spatiotemporal process that involves the intimate association between the embryo and the endometrium of the mother. During implantation, the endometrium undergoes a dynamic cascade of gene activation and repression, largely driven by autocrine, paracrine, and endocrine action. Steroid hormones, such as estrogen and progesterone, act on a variety of targets including cellular adhesion molecules (CAMs), cytokines, and growth factors to facilitate the implantation process. Given the synchrony required to achieve implantation, it is unsurprising that embryo implantation represents a substantial problem for infertility patients. This is due to a complex interplay taking place at the level of the endometrium. This review discusses the intricacies of embryo implantation including the window of implantation, the cyclical phases of the endometrium, the implantation process itself, and features of endometrial receptivity. Additionally, we will discuss new research regarding inflammatory reproductive biology, epigenetics and microRNA, and the role of the vaginal and endometrial microbiome in implantation. A better understanding of embryo implantation and the interactions occurring at the level of the blastocyst and the endometrium will improve patient care for infertile patients who experience this frustrating challenge.

A call to action: unified clinical practice guidelines for oncofertility care.

By 2030, WHO estimates that 1.4 million reproductive-aged women will be diagnosed with cancer annually. Fortunately, cancer is no longer considered an incurable disease in many cases. From 2008-2014, 85% of women under the age of 45 years diagnosed with cancer survived. This increase in survival rate has shifted attention from focusing exclusively on preserving life to focusing on preserving quality of life after treatment. One aspect of this is preserving the ability to have a biological family. Oncofertility, the field that bridges oncology and reproductive endocrinology with the goal of preserving fertility, offers these patients hope. Though it is clear that ASCO and ASRM recognize the importance of fertility preservation as an aspect of comprehensive oncology care, there are not yet unified guidelines for oncologists and fertility specialists for treating oncofertility patients. First, we identify the need for reproductive counseling prior to cancer treatment, as many patients report that their fertility preservation concerns are not addressed adequately. We then delineate multi-modal fertility preservation options that are available and appropriate for different patients with corresponding outcomes using different treatments. We discuss the unique challenges and considerations, including ethical dilemmas, for delivering timely and comprehensive care specifically for oncofertility patients. Finally, we address the multidisciplinary team that includes oncologists, reproductive endocrinologists, surgeons as well as their staff, nurses, genetic counselors, mental health professionals, and more. Since oncofertility patient care requires the coordination of both physician teams, one set of unified guidelines will greatly improve quality of care.

A 2019 reproductive update from the Midwest Reproductive Symposium International.

"Mystery, Medicine, and the Magnificent Mile," the theme for the annual Midwest Reproductive Symposium International (MRSi) in Chicago, IL, captured the attention of reproductive professionals all over the world. Each year, the conference agenda encompasses emerging technologies in assisted reproduction, updates in the management of reproductive diseases, and common challenges encountered in clinical practice. The structure of the meeting, offering a mixture of lectures, panel discussions, and interactive workshops, creates a collaborative environment for physicians, geneticists, embryologists, nurses, mental health professionals, basic scientists, business administrative professionals, reproductive endocrinology and infertility fellows, and obstetrics and gynecology residents. The goal of the MRSi meeting is to provide all reproductive professionals the opportunity to exchange ideas, foster relationships, and deliver quality patient care. As the field continues to evolve, MRSi provides an exciting venue to uncover the mysteries of reproductive medicine with enthusiasm and collaboration.

Review and recap of the Midwest Reproductive Symposium International: learning tool for continuing medical education for reproductive endocrinologists, geneticists, embryologists, mental health, and other infertility providers.

Conferences serve an essential means of learning and staying up to date in all aspects of medicine. Reproductive endocrinology and infertility is a young and constantly evolving field. The Midwest Reproductive Symposium International (MRSi) is a yearly conference held in Chicago, IL, and is one of the most intimate yet influential conferences in the fertility world. This conference is geared towards all professions and roles in the fertility world such as physicians, geneticists, nurses, allied health professionals, basic scientists, mental health professionals, business administration professionals, reproductive endocrinology and infertility fellows, and obstetrics and gynecology residents alike. The goal of MRSi is to continue to understand this revolutionary field in order to improve patient outcomes while staying up to date with the latest technology.

Essential learning tools for continuing medical education for physicians, geneticists, nurses, allied health professionals, mental health professionals, business administration professionals, and reproductive endocrinology and infertility (REI) fellows: the Midwest Reproductive Symposium International.

Essential learning tools for continuing medical education are a challenge in today's rapidly evolving field of reproductive medicine. The Midwest Reproductive Symposium International (MRSi) is a yearly conference held in Chicago, IL. The conference is targeted toward physicians, geneticists, nurses, allied health professionals, mental health professionals, business administration professionals, and reproductive endocrinology and infertility (REI) fellows engaged in the practice of reproductive medicine. In addition to the scientific conference agenda, there are specific sessions for nurses, mental health professionals, and REI fellows. Unique to the MRSi conference, there is also a separate "Business Minds" session to provide education on business acumen as it is an important element to running a department, division, or private clinic.

Patients' administration preferences: progesterone vaginal insert (Endometrin®) compared to intramuscular progesterone for Luteal phase support.

BACKGROUND: Administration of exogenous progesterone for luteal phase support has become a standard of practice. Intramuscular (IM) injections of progesterone in oil (PIO) and vaginal administration of progesterone are the primary routes of administration. This report describes the administration preferences expressed by women with infertility that were given progesterone vaginal insert (PVI) or progesterone in oil injections (PIO) for luteal phase support during fresh IVF cycles. METHODS: A questionnaire to assess the tolerability, convenience, and ease of administration of PVI and PIO given for luteal phase support was completed by infertile women diagnosed with PCOS and planning to undergo IVF. The women participated in an open-label study of highly purified human menopausal gonadotropins (HP-hMG) compared with recombinant FSH (rFSH) given for stimulation of ovulation. RESULTS: Most women commented on the convenience and ease of administration of PVI, while a majority of women who administered IM PIO described experiencing pain. In addition, their partners often indicated that they had experienced at least some anxiety regarding the administration of PIO. The most distinguishing difference between PVI and PIO in this study was the overall patient preference for PVI. Despite the need to administer PVI either twice a day or three times a day, 82.6% of the patients in the PVI group found it "very" or "somewhat convenient" compared with 44.9% of women in the PIO group. CONCLUSIONS: The results of this comprehensive, prospective patient survey, along with findings from other similar reports, suggest that PVI provides an easy-to-use and convenient method for providing the necessary luteal phase support for IVF cycles without the pain and inconvenience of daily IM PIO. Moreover, ongoing pregnancy rates with the well-tolerated PVI were as good as the pregnancy rates with PIO. TRIAL REGISTRATION: ClinicalTrial.gov, NCT00805935.

State-mandated insurance coverage is associated with the approach to hydrosalpinges before IVF.

The aim of this study was to determine whether practice in states with infertility insurance mandates is associated with physician-reported practice patterns regarding hydrosalpinx management in assisted reproduction clinics. A cross-sectional, internet-based survey of 442 members of Society for Reproductive Endocrinology and Infertility or Society of Reproductive Surgeons was performed. Physicians practising in states without infertility insurance mandates were more likely to report performing diagnostic surgery after an inconclusive hysterosalpingogram than physicians practising in states with mandates (RR 1.2, 95% CI 1.1-1.3, P < 0.01). Additionally, respondents in states without mandates were more likely to report that, due to lack of infertility insurance coverage, they did not perform salpingectomy (SPX) or proximal tubal occlusion (PTO) before assisted reproduction treatment (RR 1.4, 95% CI 1.1-1.8, P = 0.01). Finally, respondents in states without mandates were less likely to report that the presence of assisted reproduction treatment coverage determined the urgency with which they pursued SPX or PTO before treatment (RR 0.7, 95% CI 0.5-1.0, NS). These results persisted after controlling for physician years in practice, age and clinic volume. In conclusion, self-reported physician practice interventions for hydrosalpinges before assisted reproduction treatment may be associated with state-mandated infertility insurance. Fallopian tube dysfunction is a known cause of infertility and severe dysfunction is manifested by dilation and occlusion, known as hydrosalpinx. Outcomes with assisted reproductive techniques (ART) are lower when hydrosalpinges are present and while there are several theories for this, reproductive specialist recommend "neutralizing" the tube either by occlusion or removal in order to enhance pregnancy rates. In the United States, coverage for infertility services is not uniform with only 15 states having some legislation requiring infertility benefits. Some states where ART is covered liberally, physicians might have different practice patterns related to the neutralization of hydrosalpinges compared to those who are in non -mandated states. We utilized a survey of over 400 providers in the United States to examine their practice patterns as it relates to hydrosalpinges based on which state they practice in and whether or not that state has mandated coverage of not.

Endometrin as luteal phase support in assisted reproduction.

OBJECTIVE: To compare clinical pregnancy rate (PR) and live birth rate (LBR) between Endometrin monotherapy versus Endometrin and P in oil combination therapy in assisted reproductive technology (ART) cycles. DESIGN: Retrospective analysis. SETTING: Large private practice. PATIENT(S): Patients undergoing autologous fresh IVF cycles, autologous frozen ET cycles, and fresh oocyte donor cycles were included for analysis. INTERVENTION(S): Endometrin as a single agent for luteal support, Endometrin monotherapy or Endometrin with P in oil used at least once every 3 days for luteal support, Endometrin combination therapy. MAIN OUTCOME MEASURE(S): Clinical PR and LBR. RESULT(S): A total of 1,034 ART cycles were analyzed. Endometrin monotherapy was used in 694 of 1,034 (67%) cycles and Endometrin combination therapy was used in 340 of 1,034 (33%) cycles. In all fresh cycles, clinical PR was not significantly different (IVF autologous: Endometrin monotherapy 46.9% vs. Endometrin combination therapy 55.6%; donor oocyte endometrin monotherapy 45.2% vs. Endometrin combination therapy 52.0%). Frozen ET cycles had a significantly higher clinical PR and LBR with combination therapy group compared with monotherapy (clinical PR 47.9% vs. 23.5%; LBR 37.5% vs. 17.3%). CONCLUSION(S): Endometrin monotherapy was sufficient for the P component of luteal support and provided high PRs for fresh cycles in both autologous and donor oocyte cycles. Clinical PR and LBR in frozen ET cycles were significantly improved with the addition of IM P to Endometrin therapy. This may reflect the fact that lesser quality embryos are transferred in frozen ET cycles, and more intense P support is required for comparable PRs.

How members of the Society for Reproductive Endocrinology and Infertility and Society of Reproductive Surgeons evaluate, define, and manage hydrosalpinges.

OBJECTIVE: To describe the management of hydrosalpinges among Society for Reproduction Endocrinology and Infertility (SREI)/Society of Reproductive Surgeons (SRS) members. DESIGN: Cross-sectional survey of SREI/SRS members. SETTING: Academic and private practice-based reproductive medicine physicians. PARTICIPANT(S): A total of 442 SREI and/or SRS members. INTERVENTION(S): Internet-based survey. MAIN OUTCOME MEASURE(S): To understand how respondents evaluate, define, and manage hydrosalpinges. RESULT(S): Of 1,070 SREI and SRS members surveyed, 442 responded to all items, for a 41% response rate. Respondents represented both academic and private practice settings, and differences existed in the evaluation and management of hydrosalpinges. More than one-half (57%) perform their own hysterosalpingograms (HSGs), and 54.5% involve radiologists in their interpretation of tubal disease. Most respondents thought that a clinically significant hydrosalpinx on HSG is one that is distally occluded (80.4%) or visible on ultrasound (60%). Approximately one in four respondents remove a unilateral hydrosalpinx before controlled ovarian hyperstimulation (COH)/intrauterine insemination (IUI) and clomiphene citrate (CC)/IUI (29.3% and 22.8%, respectively), and physicians in private practice were more likely to intervene (COH: risk ratio [RR] 1.81, 95% confidence interval [CI] 1.31-2.51; CC: RR 1.98, 95% CI 1.33-2.95). Although laparoscopic salpingectomy was the preferred method of surgical management, nearly one-half responded that hysteroscopic tubal occlusion should have a role as a primary method of intervention. CONCLUSION(S): SREI/SRS members define a "clinically significant hydrosalpinx" consistently, and actual practice among members reflects American Society for Reproductive Medicine/SRS recommendations, with variation attributed to individual patient needs. Additionally, one in four members intervene before other infertility treatments when there is a unilateral hydrosalpinx present.

Embryo transfer practices in the United States: a survey of clinics registered with the Society for Assisted Reproductive Technology.

OBJECTIVE: To gain a better understanding of factors influencing clinicians' embryo transfer practices. DESIGN: Cross-sectional survey. SETTING: Web-based survey conducted in December 2008 of individuals practicing IVF in centers registered with the Society for Assisted Reproductive Technology (SART). PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Prevalence of clinicians reporting following embryo transfer guidelines recommended by the American Society for Reproductive Medicine (ASRM), prevalence among these clinicians to deviate from ASRM guidelines in commonly encountered clinical scenarios, and practice patterns related to single embryo transfer. RESULT(S): Six percent of respondents reported following their own, independent guidelines for the number of embryos to transfer after IVF. Of the 94% of respondents who reported routinely following ASRM embryo transfer guidelines, 52% would deviate from these guidelines for patient request, 51% for cycles involving the transfer of frozen embryos, and 70% for patients with previously failed IVF cycles. All respondents reported routinely discussing the risks of multiple gestations associated with standard embryo transfer practices, whereas only 34% reported routinely discussing single embryo transfer with all patients. CONCLUSION(S): Although the majority of clinicians responding to our survey reported following ASRM embryo transfer guidelines, at least half would deviate from these guidelines in a number of different situations.

Lower chance of pregnancy with repeated cycles with in vitro fertilization.

OBJECTIVE: To evaluate pregnancy outcomes in initial and replicate IVF cycles. STUDY DESIGN: A retrospective analysis of 2,167 fresh, nondonor IVF cycles performed in a large private practice from January 1, 2005, to March 1, 2006. Standard controlled ovarian hyperstimulation and laboratory protocols were followed. RESULTS: Patients undergoing multiple treatment cycles were significantly older. There was no difference in body mass index or percentage of cancelled cycles with increasing number of IVF attempts. The number of retrieved, mature and fertilized oocytes progressively declined as the number of treatment cycles increased. The number of embryos transferred increased with increasing number of treatment cycles. Implantation, pregnancy and clinical pregnancy rates decreased significantly with the second treatment cycle and more markedly with 3-5 treatment cycles. CONCLUSION: The likelihood of a successful outcome declined with each additional treatment cycle. The most notable decrease in clinical pregnancy rates occurred after the third cycle. Patients who fail to conceive after 3 cycles of IVF should be counseled to begin considering other options.

Body mass index: impact on IVF success appears age-related.

BACKGROUND: The objective of this study was to examine the effect of BMI on IVF outcomes. METHODS: This was a retrospective analysis of all patients undergoing IVF from 1st January 2005 to 1st March 2006 in a large private practice using a single IVF laboratory. The patients underwent standard protocols for controlled ovarian hyperstimulation and embryology parameters. The main outcome measure was clinical pregnancy rate. RESULTS: A total of 2167 fresh, non-donor IVF cycles were queried, but to minimize bias, only the first treatment cycle for each patient was analyzed (n = 1273). The data were examined by multiple regression models that included BMI and Age as main effects plus a BMI x Age interaction. When examined as a main effect, BMI did not appear to have a major effect on IVF outcome, but there was a significant BMI x Age interaction. At younger ages, a high BMI had a pronounced negative influence on fertility, but this effect diminished as the patient age increased. Clinical pregnancy rates decreased with increasing BMI and increasing Age. CONCLUSIONS: In younger patients undergoing IVF, BMI has a significant negative impact on fertility that diminishes as patients reach their mid thirties. After Age 36, BMI has a minimal impact on fertility.

Adding human menopausal gonadotrophin to antagonist protocols - is there a benefit?

The objective of this retrospective analysis was to compare the clinical outcomes of recombinant FSH (r-FSH) with combination r-FSH plus human menopausal gonadotrophin (HMG) protocols in a large private practice using a single IVF laboratory, from 2001 to 2003. Patients underwent ovarian stimulation by standard gonadotrophin-releasing hormone (GnRH) antagonist protocol using r-FSH or combination r-FSH plus HMG. When two or more follicles had attained a minimum mean diameter of 20 mm, follicular triggering was achieved with either recombinant HCG (r-HCG; Ovidrel, 250 microg s.c.) or urinary HCG (u-HCG; 10,000 IU i.m.). The main outcome measures were number of oocytes retrieved and clinical pregnancy rate. There was a lower percentage of cancelled cycles and an increased number of oocytes retrieved, mature oocytes, oocytes that fertilized, embryo that cleaved and a tendency towards higher clinical pregnancy rates in patients treated with r-FSH alone compared with those treated with r-FSH plus HMG. Patients treated with r-FSH plus HMG had lower miscarriage rates and the live birth rate was similar in both treatment groups. In conclusion, irrespective of age, using a treatment regimen consisting of a combination of HMG plus r-FSH was not beneficial compared with r-FSH alone in patients using a GnRH antagonist protocol.

Age-matched comparison of recombinant and urinary HCG for final follicular maturation.

This age-matched retrospective analysis compared the clinical outcomes of recombinant human chorionic gonadotrophin (rHCG) and urinary HCG (uHCG) in patients undergoing fresh, nondonor IVF cycles. The patients underwent ovarian stimulation by standard gonadotrophin-releasing hormone (GnRH) agonist down-regulation or a GnRH antagonist protocol using recombinant FSH (rFSH) alone or in combination with human menopausal gonadotrophin. When two or more follicles had attained a mean diameter of 20 mm, follicular triggering was achieved with either Ovidrel (rHCG) 250 mug SC or uHCG 10,000 IU IM. Patients receiving rHCG were considered subjects, and they were age-matched in a 1:2 ratio to patients receiving uHCG, who were designated as controls. The main outcome measures were number of oocytes retrieved, number of mature oocytes obtained, number of oocytes fertilized and clinical pregnancy rates. A total of 273 subjects were age-matched and compared with 546 controls. Recombinant HCG had a minimal effect on the number of oocytes retrieved (13.4 versus 13.2), mature oocytes (10.5 versus 10.3) and oocytes fertilized (8.2 versus 7.8) compared with uHCG. Pregnancy (46.0 versus 45.2%) and clinical pregnancy rates (38.1 versus 36.8%) were similar for rHCG and uHCG. Recombinant HCG was as effective as uHCG for final follicular maturation in IVF cycles.