Relationships between reproductive hormones and maternal pregnancy physiology in women conceiving with or without in vitro fertilization.

We evaluated maternal pregnancy adaptations and their relationships with circulating hormones in women who conceived with or without in vitro fertilization (IVF). Pregnancies were grouped by corpus luteum (CL) number: 1 CL with physiological plasma relaxin concentration (PRLN; spontaneous pregnancies); 0 CL without circulating RLN (programmed cycles); >1 CL with elevated PRLN (ovarian stimulation). Major findings were that declines in plasma osmolality (Posm) and plasma sodium concentration ([Formula: see text]) were comparable in the 1 CL and 0 CL cohorts, correlated with plasma estradiol and progesterone concentrations but not PRLN; gestational declines in plasma uric acid (UA) concentration (PUA) were attenuated after IVF, especially programmed cycles, partly because of subdued increases of renal UA clearance; and PRLN and cardiac output (CO) were inversely correlated when plasma estradiol concentration was below ∼2.5 ng/mL but positively correlated above ∼2.5 ng/mL. Unexpectedly, PRLN and plasma sFLT1 (PsFLT1) were directly correlated. Although PsFLT1 and CO were not significantly associated, CO was positively correlated with plasma placental growth factor (PLGF) concentration after the first trimester, particularly in women who conceived with 0 CL. Major conclusions are that 1) circulating RLN was unnecessary for gestational falls in Posm and [Formula: see text]; 2) PRLN and CO were inversely correlated during early gestation, suggesting that PRLN in the lower range may have contributed to systemic vasodilation, whereas at higher PRLN RLN influence became self-limiting; 3) evidence for cooperativity between RLN and estradiol on gestational changes in CO was observed; and 4) after the first trimester in women who conceived without a CL, plasma PLGF concentration was associated with recovery of CO, which was impaired during the first trimester in this cohort.

Implications of the vaginal microbiome and potential restorative strategies on maternal health: a narrative review.

The vaginal microbiome undergoes dramatic shifts before and throughout pregnancy. Although the genetic and environmental factors that regulate the vaginal microbiome have yet to be fully elucidated, high-throughput sequencing has provided an unprecedented opportunity to interrogate the vaginal microbiome as a potential source of next-generation therapeutics. Accumulating data demonstrates that vaginal health during pregnancy includes commensal bacteria such as Lactobacillus that serve to reduce pH and prevent pathogenic invasion. Vaginal microbes have been studied as contributors to several conditions occurring before and during pregnancy, and an emerging topic in women's health is finding ways to alter and restore the vaginal microbiome. Among these restorations, perhaps the most significant effect could be preterm labor (PTL) prevention. Since bacterial vaginosis (BV) is known to increase risk of PTL, and vaginal and oral probiotics are effective as supplemental treatments for BV prevention, a potential therapeutic benefit exists for pregnant women at risk of PTL. A new method of restoration, vaginal microbiome transplants (VMTs) involves transfer of one women's cervicovaginal secretions to another. New studies investigating recurrent BV will determine if VMTs can safely establish a healthy Lactobacillus-dominant vaginal microbiome. In most cases, caution must be taken in attributing a disease state and vaginal dysbiosis with a causal relationship, since the underlying reason for dysbiosis is usually unknown. This review focuses on the impact of vaginal microflora on maternal outcomes before and during pregnancy, including PTL, gestational diabetes, preeclampsia, and infertility. It then reviews the clinical evidence focused on vaginal restoration strategies, including VMTs.

Maternal endothelial function, circulating endothelial cells, and endothelial progenitor cells in pregnancies conceived with or without in vitro fertilization.

In women who conceived with or without assisted reproduction, we evaluated endothelial function by EndoPAT [reactive hyperemia index (RHI)], circulating numbers of endothelial cells (CEC) and endothelial progenitor cells (EPC), and their function before during and after pregnancy. In vitro fertilization (IVF) pregnancies were stratified by method of conception and corpus luteum (CL) number-controlled ovarian stimulation (>1 CL) or programmed (0 CL) cycles and spontaneous singleton pregnancies (1 CL). We observed 1) comparable gestational decline of RHI in the three participant groups secondary to gestational rise of baseline preocclusion pulse-wave amplitude (PWA) incorporated into the RHI calculation by EndoPAT software; 2) progressive rise in "normalized" RHI throughout pregnancy (calculated by substituting prepregnancy baseline preocclusion PWA into the RHI equation), greater in spontaneous conception vs. IVF cohorts; 3) similar gestational increase of maximum PWA and time to maximum PWA after the ischemia stimulus among the three participant groups; 4) modest gestational increase of ischemia response (reactive hyperemia) in the spontaneous conception group and no change or significant decline, respectively, in women who conceived using programmed or controlled ovarian stimulation cycles; 5) enhanced basal nitric oxide production by early (primitive) outgrowth EPC during pregnancy in women who conceived spontaneously, but not through IVF; and 6) gestational increase in CEC in all three participant cohorts, more pronounced in women who conceived by IVF using programmed cycles. On balance, the evidence supported enhanced endothelial function during pregnancy in spontaneous conceptions but less so in IVF pregnancies using either controlled ovarian stimulation or programmed cycles.

Fertility preservation in breast cancer with case-based examples for guidance.

With more young breast cancer survivors, a trend toward having children later in life, and improvements in assisted reproductive technology (ART), fertility preserving techniques are of growing importance prior to initiation of gonadotoxic treatments. The American Society for Clinical Oncology (ASCO) updated their Fertility Preservation in Patients with Cancer guidelines in April of 2018. ASCO continues to recognize oocyte and embryo cryopreservation as standard practice for women interested in preserving fertility and sperm cryopreservation as standard practice for men. ASCO has clarified their statement on ovarian suppression during chemotherapy as an option when standard methods are unavailable but should not be used as the sole method of fertility preservation (FP) due to conflicting evidence. ASCO also updated their statement on ovarian tissue cryopreservation, which is still labeled experimental but ASCO acknowledges that it can restore global ovarian function and could be of use in specific patients. The NCCN's Version 1.2018 Clinical Practice Guidelines® for treatment of breast cancer include fertility counseling as part of their work-up in all types of breast cancer for premenopausal women.The purpose of this review is to explain the indications and evidence for the different methods of FP for young breast cancer patients in accordance with ASCO and NCCN guidelines. The guidance will then be applied to three theoretical clinical cases in order to highlight actual use in clinical practice.

Potential influence of the corpus luteum on circulating reproductive and volume regulatory hormones, angiogenic and immunoregulatory factors in pregnant women.

Cardiovascular function is impaired and preeclampsia risk elevated in women conceiving by in vitro fertilization (IVF) in the absence of a corpus luteum (CL). Here, we report the serial evaluation of hormones and other circulating factors in women who conceived with (or without) IVF. After a prepregnancy baseline, the study participants (n = 19-24/cohort) were evaluated six times during pregnancy and once postpartum (~1.6 yr). IVF pregnancies were stratified by protocol and CL number, i.e., ovarian stimulation (>1 CL) or hypothalamic-pituitary suppression (0 CL) versus spontaneous conceptions (1 CL). Results include the following: 1) relaxin was undetectable throughout pregnancy (including late gestation) in the 0 CL cohort, but markedly elevated in ~50% of women in the >1 CL cohort; 2) progesterone, plasma renin activity, and aldosterone transiently surged at 5-6 gestational weeks in the >1 CL group; 3) soluble vascular endothelial growth factor-1 (sFLT-1) abruptly increased between 5-6 and 7-9 gestational weeks in all three participant cohorts, producing a marked elevation in sFLT-1/PLGF (placental growth factor) ratio exceeding any other time point during pregnancy; 4) sFLT-1 was higher throughout most of gestation in both IVF cohorts with or without abnormal obstetrical outcomes; 5) during pregnancy, C-reactive protein (CRP) increased in 0 and 1 CL, but not >1 CL cohorts; and 6) plasma protein, but not hemoglobin, was lower in the >1 CL group throughout gestation. The findings highlight that, compared with spontaneously conceived pregnancy, the maternal milieu of IVF pregnancy is not physiologic, and the specific perturbations vary according to IVF protocol and CL status.

The National Physicians Cooperative: transforming fertility management in the cancer setting and beyond.

Once unimaginable, fertility management is now a nationally established part of cancer care in institutions, from academic centers to community hospitals to private practices. Over the last two decades, advances in medicine and reproductive science have made it possible for men, women and children to be connected with an oncofertility specialist or offered fertility preservation soon after a cancer diagnosis. The Oncofertility Consortium's National Physicians Cooperative is a large-scale effort to engage physicians across disciplines - oncology, urology, obstetrics and gynecology, reproductive endocrinology, and behavioral health - in clinical and research activities to enable significant progress in providing fertility preservation options to children and adults. Here, we review the structure and function of the National Physicians Cooperative and identify next steps.

Case-based care for pre-existing or new-onset mood disorders in patients undergoing infertility therapy.

The inability to conceive is an immensely stressful event in a woman's life. Thus, it is no surprise that women with infertility have twice the rates of depressive symptoms as women without infertility. Incidence of depression in the general female population is approximately 20% compared to almost 40% in infertile females. Based on this information, we expect many individuals with infertility to have pre-existing mood disorders requiring ongoing treatment. In addition, we expect a subset of women to develop a mood disorder during infertility treatment due to related stressors. The reproductive endocrinology team must understand the impact of stress on pregnancy outcomes, the types of treatment options, and the safety and use of various medications. The goal of this case-based commentary is to summarize information on the relationship between stress and infertility and to offer a guide for a range of treatment options that include non-pharmacologic and pharmacologic therapies.

Sperm preservation and neutron contamination following proton therapy for prostate cancer study.

BACKGROUND: The present study investigates the impact of scatter dose radiation to the testis on ejaculate and sperm counts from treatment of prostate cancer with passive-scatter proton therapy. MATERIAL AND METHODS: From March 2010 to November 2014, 20 men with low- or intermediate-risk prostate cancer enrolled in an IRB-approved protocol and provided a semen sample prior to passive-scatter proton therapy and 6-12 months following treatment. Men were excluded if they had high-risk prostate cancer, received androgen deprivation therapy, were on alpha blockers (due to retrograde ejaculation) prior to treatment, had baseline sperm count <1 million, or were unable to produce a pre-treatment sample or could not provide a follow-up specimen. Sperm counts of 0 were considered azoospermia and <15 million/ml were classified as oligospermia. RESULTS: Four patients were unable to provide a sufficient quantity of semen for analysis. Among the 16 remaining patients, only one was found to have oligospermia (7 million/ml). There was a statistically significant reduction in semen volume (median, 0.5 ml) and increase in pH (median 0.5). Although not statistically significant, there appeared to be a decline in sperm concentration (median, 16 million/ml), total sperm count (median, 98.5 million), normal morphology (median, 9%), and rapid progressive motility (median, 9.5%). DISCUSSION: Men did not have azoospermia 6-12 months following passive-scatter proton therapy indicating minimal scatter radiation to the testis during treatment. Changes in semen quantity and consistency may occur due to prostate irradiation, which could impact future fertility and/or sexual activity.

Laparoscopic Ovarian Transposition Before Pelvic Cancer Treatment: Ovarian Function and Fertility Preservation.

Survivors of pelvic cancer treatment live with the ramifications of pelvic radiation for many years after their cure. Several options are available to preserve ovarian function and fertility in reproductive age women undergoing pelvic radiation. Laparoscopic ovarian transposition is an under-utilized, yet fairly simple surgical procedure to relocate the ovaries away from the radiation field. Although randomized-controlled trials on the outcomes of ovarian transposition are scarce, there is a growing body of evidence on the risks and benefits of this procedure, in terms of prevention of premature ovarian failure, and potentially preserving fertility. In this review, we summarize the available data on the indications, patient selection and outcomes of ovarian transposition, as well as illustrate the technique of the procedure.

The Mayo, Cushing, and Osler Influence on A. L. Rhoton: A Historical Vignette of the Interconnectedness Between Highly Influential Neurosurgery Leaders over 100 Years.

The careers of the Mayo brothers, Harvey Cushing, and Sir William Osler greatly shaped medical and surgical practice in the late 19th century and early 20th century and created a legacy to influence decades of physicians to follow. Additionally, these individuals were instrumental in the founding of neurosurgery as a distinct surgical specialty. Alongside these great men, Dr. Albert L. Rhoton Jr., revolutionized neurosurgical practice through his study of neuroanatomy and development of microsurgical technique in the second half of the 20th century. This review of the interactions and relationships between the Mayo brothers, Cushing, and Osler and their influences on Rhoton highlights the 100-year-long interconnectedness shared between these giants in the history of neurosurgery.

Fertility in the Digital Age: A Survey-Based Evaluation of Fertility App Users' Quality of Life.

This study sought to characterize fertility app use among women seen for infertility care and to investigate the association between fertility app use and quality of life. This survey-based study was conducted at an academic infertility clinic. Surveys were administered to patients who presented for a new infertility visit. One survey collected information regarding app use and the second survey was FertiQoL, an internationally validated instrument measuring quality of life in those with infertility. Descriptive statistics were used to characterize the patient population regarding app use and FertiQoL scores. Comparisons between those who did and didn't use an app were evaluated using t-tests and Cochran Armitage test for trend. 149 surveys were collected. Most (75.5%) participants reported using a fertility app. Most participants (85.1%) used a free app and nearly all (97.2%) found their app helpful. There was a significant difference (p = 0.0034) in satisfaction with one's quality of life between app users and non-app users with app users demonstrating higher satisfaction. There were no significant differences between app users and non-app users with their overall FertiQoL scores however there was a statistically significant difference (p = 0.031) in Relational sub-scores with app users displaying higher scores. While overall quality of life, measured by standardized measures, did not differ, self-perceived satisfaction with quality of life improved with more satisfaction reported in those using an app. This self-perceived satisfaction and increased quality of life surrounding relationships carries important implications, especially when one may face the stress of infertility and its treatment.

Fertility Preservation Knowledge, Attitudes, and Self-Reported Behaviors of Resident Physicians.

Purpose: Fertility preservation (FP) and family building are important considerations for quality survivorship for young cancer patients. Resident physicians across all specialties encounter reproductive-aged cancer patients. The purpose of this study was to assess resident physicians' attitudes and awareness about FP with the goal to identify specific educational gaps to direct future training. Methods: The Institutional Review Board (IRB)-approved anonymous online survey was sent to resident physicians across specialties at three separate academic-affiliated campuses in one state. The survey consisted of three sections: awareness about FP options and knowledge about referral placement, attitudes and comfort levels discussing FP, and practices regarding FP. Data were collected in Qualtrics and analyzed by resident specialty, age, level of training, and gender. Statistical analyses were conducted with Prism. Results: Obstetrics and gynecology residents and fellows were significantly more aware of FP options in cancer patients than their counterparts in other specialties. Postgraduate year (PGY 3) residents and beyond were more aware of at least one male and one female FP option compared with PGY 1 and 2 residents. Of importance, we found that the majority of resident physicians are aware of FP options and the referral process, but they are uncomfortable discussing these techniques with their patients. Conclusion: To provide better education for patients, focus should be on outpatient educational activities for both the health care provider and the patient to facilitate conversation about FP.

COVID-19: changing the care process for women's health-the patient's perspective.

OBJECTIVE: Assess women's perceptions of the impact of COVID-19 on their health care and well-being, access to and satisfaction with medical care due to the changes in delivery of care triggered by the pandemic. METHODS: An online survey of women having health care appointments in the outpatient facilities across all divisions of a Department of Obstetrics and Gynecology at a tertiary care referral center in North Central Florida. Patients had outpatient appointments that were scheduled, canceled or rescheduled, in person or by telemedicine, between 11 March 2020 and 11 May 2020, a time during which a COVID-19 stay-at-home order was enacted across our state. A total of 6,697 visits were planned. Patients with multiple visits were unified, leaving 6,044 unique patients to whom the survey was emailed between 20 July 2020 and 31 July 2020. The survey was closed on 21 August 2020. Analyses were focused on simple descriptive statistics to assess frequency of responses. Analyses of variance and chi-square analyses were conducted to compare outcomes when all cells were ≥ 10, based on sub-specialty and insurance status; otherwise, frequencies were examined for the entire sample only. Missing data were excluded listwise. RESULTS: A total of 6044 patients were contacted. Completed surveys numbered 1,083 yielding a response rate of 17.9%. The most common sub-specialty visit was gynecology (56.7%) followed by obstetrics (31.5%,), pelvic floor disorders (4.8%), gynecological oncology (2.9%,), and reproductive endocrinology (0.5%). A substantial percentage of women had visits canceled (19.2%), rescheduled (32.8%) or changed (42.1%) to telemedicine. In our patient population, 32.6% were worried about visiting the clinic and 48.1% were worried about visiting the hospital. COVID-19 triggered changes were perceived to have a negative impact by 26.1% of respondents. Refusal of future telemedicine visits was by 17.2%, however, 75.2% would prefer to use both in-person and telemedicine visits. CONCLUSION: During the initial COVID-19 surge with lockdown, the majority of survey respondents were following public health precautions. However, there were significant concerns amongst women related to obstetric and gynecologic medical appointments scheduled during that period. During pandemics, natural disasters and similar extreme circumstances, digital communication and telemedicine have the potential to play a critical role in providing reassurance and care. Nevertheless, given the concerns expressed by survey respondents, communication and messaging tools are needed to increase comfort and ensure equity with the rapidly changing methods of care delivery.

Methods of Ovarian Tissue Cryopreservation: Is Vitrification Superior to Slow Freezing?-Ovarian Tissue Freezing Methods.

After cancer treatment, female survivors often develop ovarian insufficiency or failure. Oocyte and embryo freezing are well-established fertility preservation options, but cannot be applied in pre-pubescent girls, in women with hormone-sensitive malignancies, or when gonadotoxic treatment cannot be delayed. Although ovarian tissue cryopreservation (OTC) has been used to restore fertility and endocrine function, the relative efficacy of its two major protocols, slow freezing and vitrification, remains controversial. This literature review evaluates clinical and lab-based studies published between January 2012 and June 2020 to determine whether vitrification, the optimal technique for oocyte and embryo cryopreservation, preserves ovarian tissue more effectively than slow freezing. Due to limited clinical data involving ovarian tissue vitrification, most clinical studies focus on slow freezing. Only 9 biochemical studies that directly compare the effects of slow freezing and vitrification of human ovarian tissue were noted. Most studies report no significant difference in follicular morphology and distribution between cryopreservation methods, but these findings must be interpreted in the context of high methodological variability. Discrepant findings regarding the effects of cryopreservation method on follicle viability, gene expression, and hormone production require further evaluation. Early clinical outcomes appear favorable for vitrification, but additional studies and longer term follow-up are needed to establish its efficacy. Sharing data through national or international registries would expedite this analysis. However, even if research corroborates conclusions of no clinical or biochemical difference between cryopreservation methods, the decreased costs and increased efficiency associated with vitrification make this method more accessible and cost-effective.

Feasibility and efficacy of ultrasonographic and laparoscopic guidance for microwave ablation of clinically normal canine ovaries.

OBJECTIVE: To determine the optimal energy profile for and to assess the feasibility and efficacy of ultrasonographic and laparoscopic guidance for microwave ablation (MWA) of clinically normal canine ovaries. SAMPLE: 44 extirpated ovaries from 22 healthy dogs. PROCEDURES: In the first of 2 trials, 13 dogs underwent oophorectomy by routine laparotomy. Extirpated ovaries underwent MWA at 45 W for 60 (n = 11) or 90 (12) seconds; 3 ovaries did not undergo MWA and served as histologic controls. Ovaries were histologically evaluated for cell viability. Ovaries without viable cells were categorized as completely ablated. Histologic results were used to identify the optimal MWA protocol for use in the subsequent trial. In the second trial, the ovaries of 9 dogs underwent MWA at 45 W for 90 seconds in situ. Ultrasonographic guidance for MWA was deemed unfeasible after evaluation of 1 ovary. The remaining 17 ovaries underwent MWA with laparoscopic guidance, after which routine laparoscopic oophorectomy was performed. Completeness of ablation was histologically assessed for all ovaries. RESULTS: 2 ovaries were excluded from the trial 1 analysis because of equivocal cell viability. Six of 11 ovaries and 10 of 10 ovaries that underwent MWA for 60 and 90 seconds, respectively, were completely ablated. In trial 2, laparoscopic-guided MWA resulted in complete ablation for 12 of 17 ovaries. Dissection of the ovarian bursa for MWA probe placement facilitated complete ablation. CONCLUSIONS AND CLINICAL RELEVANCE: Laparoscopic-guided MWA at 45 W for 90 seconds was feasible, safe, and effective for complete ablation of clinically normal ovaries in dogs.

Postnatal pediatric systemic antibiotic episodes during the first three years of life are not associated with mode of delivery.

BACKGROUND: Delivery by cesarean section (C-section) is associated with adverse short-term and long-term infant outcomes. Given that antibiotics during early life are prescribed for infant outcomes that are more likely among c-section deliveries, we hypothesized that postnatal antibiotic exposure will be greater among c-section infants compared to vaginally delivered infants. OBJECTIVE: The aim of this paper was to evaluate if mode of infant delivery was associated with patterns of systemic antibiotic exposure in children during their first three years. METHODS: Pediatric electronic health records from UFHealth, 2011 to 2017 were reviewed. We included singleton, term infants (37-42 weeks gestation) with a birth weight ≥ 2500 grams, with documented mode of delivery and well visits on record. Infants with a neonatal intensive care unit stay were excluded. Both oral and intravenous antibiotics for a 10-day duration were classified as a single episode. The primary outcome was antibiotic episodes in the first three years of life, and a sub-analysis was performed to compare broad-spectrum versus narrow-spectrum antibiotic exposures. RESULTS: The mean number of antibiotic episodes in 4,024 full-term infants was 0.34 (SD = 0.79) and 24.1% of infants had at least one antibiotic episode. Penicillins were the most prescribed antibiotic in children 0-1 years (66.9%) and cephalosporins were the most common antibiotic prescribed for children 1-3 years (56.2%). We did not detect a meaningful or significant rate ratio (RR) between mode of delivery and overall antibiotic episodes 1.14 (95% CI 0.99, 1.31), broad-spectrum episodes 1.19 (95% CI 0.93, 1.52, or narrow-spectrum episodes 1.14 (95% CI 0.97, 1.34). CONCLUSION: Our results do not support the hypothesis that postnatal antibiotic exposure was greater among infants delivered by cesarean section compare to infants delivered vaginally during the first three years of life.

The Neuroanatomy of Reproduction: Seeing Is Believing.

The brain is the central controller of reproduction and the menstrual cycle. Reproductive endocrinologists spend their days treating patients with perturbations in reproduction as a result of pituitary diseases and manipulate pituitary hormones to enhance fertility and quality of life. Microscopic neuroanatomical images will allow a better understanding of how a tumor in the pituitary might affect vision, or a mass in the brain might cause amenorrhea. Clinical correlations that are taught every day become much clearer once the anatomical relationships are explored. The objective of this pictorial tour is to elucidate anatomical and clinical relationships while showcasing the neuroanatomy of reproduction.

Maternal Cardiovascular Dysregulation During Early Pregnancy After In Vitro Fertilization Cycles in the Absence of a Corpus Luteum.

Commonly used in vitro fertilization protocols produce pregnancies without a corpus luteum (CL), a major source of reproductive hormones. In vitro fertilization pregnancies without a CL showed deficient gestational increases of central (aortic) arterial compliance during the first trimester and were at increased risk for developing preeclampsia. Here, we investigated whether there was generalized impairment of cardiovascular adaptation in in vitro fertilization pregnancies without a CL compared with pregnancies conceived spontaneously or through ovarian stimulation, which lead to 1 and >1 CL, respectively (n=19-26 participants per cohort). Prototypical maternal cardiovascular adaptations of gestation were serially evaluated noninvasively, initially during the follicular phase before conception, 6× in pregnancy, and then, on average, 1.6 years post-partum. The expected increases of cardiac output, left atrial dimension, peak left ventricular filling velocity in early diastole (E wave velocity), peripheral/central arterial pulse pressure ratio, and global AC, as well as decrease in augmentation index were significantly attenuated or absent during the first trimester in women who conceived without a CL, when compared with the 1 and >1 CL cohorts, which were comparable. Thereafter, these cardiovascular measures showed recovery in the 0 CL group except for E wave velocity, which remained depressed. These results provided strong support for a critical role of CL factor(s) in the transformation of the maternal cardiovascular system in early gestation. Regimens that lead to the development of a CL or replacement of missing CL factor(s) may be indicated to improve cardiovascular function and reduce preeclampsia risk in in vitro fertilization pregnancies.

Increased Preeclampsia Risk and Reduced Aortic Compliance With In Vitro Fertilization Cycles in the Absence of a Corpus Luteum.

In vitro fertilization involving frozen embryo transfer and donor oocytes increases preeclampsia risk. These in vitro fertilization protocols typically yield pregnancies without a corpus luteum (CL), which secretes vasoactive hormones. We investigated whether in vitro fertilization pregnancies without a CL disrupt maternal circulatory adaptations and increase preeclampsia risk. Women with 0 (n=26), 1 (n=23), or >1 (n=22) CL were serially evaluated before, during, and after pregnancy. Because increasing arterial compliance is a major physiological adaptation in pregnancy, we assessed carotid-femoral pulse wave velocity and transit time. In a parallel prospective cohort study, obstetric outcomes for singleton livebirths achieved with autologous oocytes were compared between groups by CL number (n=683). The expected decline in carotid-femoral pulse wave velocity and rise in carotid-femoral transit time during the first trimester were attenuated in the 0-CL compared with combined single/multiple-CL cohorts, which were similar (group-time interaction: P=0.06 and 0.03, respectively). The blunted changes of carotid-femoral pulse wave velocity and carotid-femoral transit time from prepregnancy in the 0-CL cohort were most striking at 10 to 12 weeks of gestation ( P=0.01 and 0.006, respectively, versus 1 and >1 CL). Zero CL was predictive of preeclampsia (adjusted odds ratio, 2.73; 95% CI, 1.14-6.49) and preeclampsia with severe features (6.45; 95% CI, 1.94-25.09) compared with 1 CL. Programmed frozen embryo transfer cycles (0 CL) were associated with higher rates of preeclampsia (12.8% versus 3.9%; P=0.02) and preeclampsia with severe features (9.6% versus 0.8%; P=0.002) compared with modified natural frozen embryo transfer cycles (1 CL). In common in vitro fertilization protocols, absence of the CL perturbed the maternal circulation in early pregnancy and increased the incidence of preeclampsia.

Wave reflections and global arterial compliance during normal human pregnancy.

Profound changes occur in the maternal circulation during pregnancy. Routine measures of arterial function - central systolic pressure (CSP) and augmentation index (AIx) - decline during normal human pregnancy. The objectives of this study were twofold: (1) explore wave reflection indices besides CSP and AIx that are not routinely reported, if at all, during normal human pregnancy; and (2) compare wave reflection indices and global arterial compliance (gAC) obtained from carotid artery pressure waveforms (CAPW) as a surrogate for aortic pressure waveforms (AOPW) versus AOPW synthesized from radial artery pressure waveforms (RAPW) using a generalized transfer function. To our knowledge, a comparison of these two methods has not been previously evaluated in the context of pregnancy. Ten healthy women with normal singleton pregnancies were studied using applanation tonometry (SphygmoCor) at pre-conception, and then during 10-12 and 33-35 gestational weeks. CSP and AIx declined, and gAC increased during pregnancy as previously reported. As a consequence of the rise in gAC, the return of reflected waves of lesser magnitude from peripheral reflection sites to the aorta was delayed that, in turn, reduced systolic duration of reflected waves, augmentation index, central systolic pressure, LV wasted energy due to reflected waves, and increased brachial-central pulse pressure. For several wave reflection indices, those derived from CAPW as a surrogate for AOPW versus RAPW using a generalized transfer function registered greater gestational increases of arterial compliance. This discordance may reflect imprecision of the generalized transfer function for some waveform parameters, though potential divergence of carotid artery and aortic pressure waveforms during pregnancy cannot be excluded.