Lower Pregnancy and Live Birth Rates with Vaginal Endometrin Plus Intramuscular Progesterone Every Third Day Versus Intramuscular Progesterone Alone in Programmed Frozen Embryo Transfers: A Retrospective Case-control Study.

This study aimed to determine whether the use of vaginal Endometrin plus intramuscular progesterone on every third day (VIM) in programmed frozen embryo transfer (FET) is associated with lower pregnancy and live birth rates compared to daily intramuscular progesterone (IM). FET data from a single program were collected between November 2018 and December 2021. A total of 903 FETs were analyzed, including 504 FETs in the IM group, and 399 FETs in the VIM group. Inclusion criteria were women undergoing FETs with either 50 mg daily IM progesterone only (control) or 200 mg Endometrin twice daily plus 50 mg IM progesterone on every third day, with the transfer of a single day 5 or 6 frozen embryo. There were no significant differences in patient age at time of FETs, BMI, endometrial thickness, blastocyst quality, or infertility diagnosis between the groups. The VIM had significantly lower positive hCG and clinical pregnancy rates compared to the IM (60.2% vs 72.0% and 40.6% vs 56.7%, respectively, P = 0.0002 and P < 0.0001). The live birth rate was 36.1% in the VIM, compared to 49.4% in the IM (P < 0.0001). These findings also remained significant when excluding FETs with donor egg (35.9% vs 50.1%, P < 0.0001). This study demonstrated that VIM in FET cycles yields significantly lower pregnancy and live birth rates compared to IM along. IM progesterone alone may be preferable to combined Endometrin and IM progesterone in patients undergoing programmed frozen embryo transfers.

Vanquishing multiple pregnancy in in vitro fertilization in the United States-a 25-year endeavor.

The practice of in vitro fertilization has changed tremendously since the birth of the first in vitro fertilization infant in 1978. With the success of early in vitro fertilization programs in the United States, there was a substantial rise in twin births nationwide. In the mid-1990s, more than 30% of in vitro fertilization cycles resulted in twin or higher-order multifetal pregnancies. Since that time, we not only have witnessed improvements in laboratory and treatment efficacy but also have seen a dramatic impact on pregnancy outcomes, specifically regarding twin pregnancies. Because the field evolved and the risks of multifetal pregnancies became more salient, in 2019, the rate of twin pregnancies had dropped to <7% of cycles. This improvement was largely because of technical advancements and revised professional guidance: culturing embryos longer before transfer, improved freezing technology, embryo preimplantation genetic testing, and revised professional guidance regarding the number of embryos to transfer. These developments have led to single-embryo transfer becoming the standard of care in most scenarios. We used national in vitro fertilization surveillance data of all autologous in vitro fertilization cycles from 1996 to 2019 to illustrate trends in the following improved outcomes: autologous embryo transfer cycles involving blastocyst-stage embryos, vitrified embryos, preimplantation genetic testing cycles, total number of embryos being transferred per cycle, and single-embryo transfer usage over time. Among deliveries from autologous embryo transfers, we highlighted trends in singleton births over time and proportion of deliveries involving twins, triplets, quadruplets, or greater. The notable progress in reducing the rate of multifetal pregnancies with in vitro fertilization was largely attributed to a series of technical and clinical actions, culminating in an 80% reduction in the incidence of multiple births without a loss in overall treatment effectiveness.

Changing gender gap and practice patterns in reproductive endocrinology and infertility subspecialists in the United States: a Society for Reproductive Endocrinology and Infertility report.

OBJECTIVE: To identify changes in current practice patterns, salaries, and satisfaction by gender and by years in practice among board-certified reproductive endocrinology and infertility (REI) subspecialists in the United States. DESIGN: Cross-sectional web-based survey including 37 questions conducted by the Society for Reproductive Endocrinology and Infertility. SETTING: Not applicable. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary outcome measures were total compensation and practice patterns compared by gender and the type of practice. The secondary outcomes included demographics, the number of in vitro fertilization cycles, surgeries performed, and the morale of survey respondents. RESULT(S): There were 370 respondents (48.4% women and 51.4% men). Compared with a similar survey conducted 6 years earlier, a 27% increase in the number of female respondents was observed in this survey. There was a marginally significant trend toward lower compensation for female than male REI subspecialists (17% lower, $472,807 vs. $571,969). The gap was seen for responders with ≥10 years' experience, which is also when there was the largest gap between private and academic practice (mean $820,997 vs, $391,600). Most (77%) felt positively about the current state of the reproductive endocrinology field, and >90% would choose the subspecialty again. CONCLUSION(S): There has been a substantial increase in the number of recent female REI subspecialists showing less disparity in compensation, and the gap appears to be closing. There is an increasing gap in compensation between private and academic practices with ≥5 years of experience. Reproductive endocrinology and infertility remains a high morale specialty.

A Fluid-Management Drape for Hysteroscopy: Innovation for Improved Patient Safety and Surgical Care.

BACKGROUND: Hysteroscopy requires accurate collection of unabsorbed distension media to measure patient fluid absorption. We assessed the effectiveness and usability of a novel total capture drape compared with a standard drape during hysteroscopy. METHOD: Simulation trials were followed by an early-phase study to compare fluid-capture efficiency and measures of drape usability during hysteroscopy randomizing the total capture drape compared with a standard drape. EXPERIENCE: Simulation trials indicated complete collection of unabsorbed fluid with the total capture drape and progressive loss of unabsorbed fluid with the standard drape. An early-phase study with 68 women found no statistical difference between groups for the hysteroscopic fluid deficit, but saw fewer cases with lost fluid in the total capture drape compared with the standard drape. Direct observation and focus group data indicated a trend for better capture of unabsorbed fluid with the total capture drape, along with increased usability once surgeons became familiar with correct placement. CONCLUSION: Simulation and early-phase study results are favorable for the total capture drape, demonstrating comparable fluid collection with the standard drape. With repeated use and in-service training, surgeons expressed greater confidence in the accuracy of the hysteroscopic fluid deficit with the total capture drape compared with the standard drape. Design modifications should improve overall usability and fluid-capture efficiency.

Academic pursuits in board-certified reproductive endocrinologists.

OBJECTIVE: To determine research interests of reproductive endocrinology and infertility (REI) physicians and assess their academic productivity. DESIGN: A questionnaire composed by the Society for REI (SREI) board members was e-mailed to members. PubMed was queried to quantify peer-reviewed publications. SETTING: An internal SREI questionnaire to members and online publication search. PATIENT(S): Not applicable. INTERVENTION(S): Questions involving research being performed, funding, relevance to fellow thesis, and important areas of future research. Publications were ascertained in the past 3 years, past 10 years, and total publications for SREI members. MAIN OUTCOME MEASURE(S): Question responses and number of peer-reviewed publications. RESULT(S): Most respondents currently conduct research, which was predominantly clinical. One-third have current research funding and two-thirds were ever funded. One-third had a National Institutes of Health grant and about half were principal investigators. Two-thirds had a basic science fellow thesis and 44% of respondents perform research related to their fellowship thesis. Important research areas included infertility outcomes, implantation, preimplantation genetic testing, and genetics. In the past 3 years, SREI members published 3,408 peer-reviewed articles (mean ± standard deviation [SD], 4.4 ± 9.0). In the past 10 years, SREI members had 10,162 peer-reviewed publications (mean±SD, 13.0 ± 24.3). When all publications were considered, SREI members published 24,088 peer-reviewed articles (mean±SD, 30.9 ± 53.0). CONCLUSION(S): The REI fellows have learned to construct scientific articles, which will help them to better interpret the literature in the care of patients. The SREI members continue to pursue scientific investigation, commonly related to their fellowship thesis. Respondents support SREI funding research; the success of which should be judged by publications. Overall, SREI members have demonstrated significant academic productivity and published about 1,000 articles/year for the past 10 years, affirming the importance of research training.

A Repeated Measures Pilot Comparison of Trajectories of Fluctuating Endogenous Hormones in Young Women with Traumatic Brain Injury, Healthy Controls.

OBJECTIVE: To compare baseline and 72-hour hormone levels in women with traumatic brain injury (TBI) and controls. SETTING: Hospital emergency department. PARTICIPANTS: 21 women ages 18-35 with TBI and 21 controls. DESIGN: Repeated measures. MAIN MEASURES: Serum samples at baseline and 72 hours; immunoassays for estradiol (E2), progesterone (PRO), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and cortisol (CORT); and health history. RESULTS: Women with TBI had lower E2 (p = 0.042) and higher CORT (p = 0.028) levels over time. Lower Glasgow Coma Scale (GSC) and OCs were associated with lower FSH (GCS p = 0.021; OCs p = 0.016) and higher CORT (GCS p = 0.001; OCs p = 0.008). CONCLUSION: Acute TBI may suppress E2 and increase CORT in young women. OCs appeared to independently affect CORT and FSH responses. Future work is needed with a larger sample to characterize TBI effects on women's endogenous hormone response to injury and OC use's effects on post-TBI stress response and gonadal function, as well as secondary injury.

The association between fatty acid index and in vitro fertilization outcomes.

PURPOSE: Fatty acids have been shown to play an important role in oocyte competence and early implantation of the embryo. Our hypothesis-generating study sought to determine if individual fatty acids expressed as a percentage of total erythrocyte fatty acids are associated with embryo quality and other in vitro fertilization (IVF) outcomes. METHODS: This was a prospective cohort study at an academic fertility center. Sixty women undergoing their first IVF cycle were recruited. Serum measurements of 22 fatty acids were obtained. We calculated each fatty acid as a percentage of total fatty acids, defined as the index for that individual fatty acid. RESULTS: Omega-3 index had no correlation with IVF outcomes. A negative correlation was found between the trans fatty acid index, elaidic acid (EA), and IVF outcomes, including fertilization rate (r = - 0.261, p = 0.04), blastocyst conversion rate (r = - 0.41, p = 0.001), and number of usable blastocysts and embryos (r = - 0.411, p = 0.001). There was no correlation between EA index and number of oocytes retrieved, embryo grade, or clinical pregnancy. No consistent correlations were observed with the additional fatty acids analyzed. CONCLUSIONS: No correlation was observed between omega-3 index and IVF outcomes. Elevated erythrocyte EA index, the major trans fatty acid commonly consumed in hydrogenated oils, margarine, and fried foods, was negatively correlated with number of usable blastocysts and embryos, blastocyst conversion, and fertilization rate. Our findings suggest preliminary evidence that trans fat may be negatively associated with IVF outcomes.

Sexual absorption of vaginal progesterone: a randomized control trial.

Objective. To determine if sexual intercourse reduces absorption of vaginal progesterone gel in women and to determine if progesterone is absorbed by the male during intercourse. Study Design. Prospective, randomized, cross over, controlled study of 20 reproductive-aged women and their male sexual partners randomized to receive vaginal progesterone gel (Crinone 8% gel, Actavis Inc., USA) or placebo cream. Serum progesterone for both male and female partners were measured 10 hours after intercourse. One week later, subjects were crossed over to receive the opposite formulation. In the third week, women used progesterone gel at night and abstained from intercourse. Results. Serum progesterone was significantly reduced with vaginal progesterone gel + intercourse compared with vaginal progesterone gel + abstinence (P = 0.0075). Men absorbed significant progesterone during intercourse with a female partner using vaginal progesterone gel compared to placebo (P = 0.0008). Conclusion(s). Vaginal progesterone gel is reduced in women after intercourse which may decrease drug efficacy during luteal phase support. Because men absorb low levels of progesterone during intercourse, exposure could cause adverse effects such as decreased libido. This study is registered under Clinical Trial number NCT01959464.

Influence of ejaculatory abstinence on seminal total antioxidant capacity and sperm membrane lipid peroxidation.

OBJECTIVE: To determine whether the period of ejaculatory abstinence (EA) influences the total antioxidant capacity (TAC) of semen or lipid peroxidation (LPO) of sperm membranes. DESIGN: A prospective experimental trial. SETTING: Academic medical center for reproductive endocrinology and infertility. PATIENT(S): Forty men from infertile couples planning intrauterine insemination. INTERVENTION(S): Men provided semen specimens after EA periods of 1 and 4 days. MAIN OUTCOME MEASURE(S): Semen analysis, peroxidase staining, and assays for seminal TAC and sperm membrane LPO, with measures compared between days 1 and 4 within individuals (internal control) using paired t tests. RESULT(S): The shorter period of EA (1 day vs. 4 days) resulted in statistically significant decreases in semen volume (-24%), sperm density (-28%), and total sperm count (-3.2%). There was a statistically significant increase in TAC with the shorter period of EA (1 day) compared with 4 days of EA. No difference was detected in sperm membrane LPO comparing 1 day of EA and 4 days of EA. CONCLUSION(S): Higher seminal TAC obtained after a shorter period of EA could diminish oxidative stress-induced sperm damage by a mechanism independent of LPO. Shorter periods of EA may thus improve sperm quality by protecting from reactive oxygen species damage, even though lower numbers of motile sperm are produced after a shorter period of EA. This would be consistent with prior research indicating improved results after intrauterine insemination under these circumstances.

Obstetric and gynecologic challenges in women with Ehlers-Danlos syndrome.

OBJECTIVE: To determine how often women with Ehlers-Danlos syndrome experience obstetric and gynecologic issues both compared with the general population and within the three most common subtypes of Ehlers-Danlos syndrome. METHODS: An anonymous, prospective, online questionnaire in English was posted to the Ehlers-Danlos National Foundation web site (http://ednf.org). RESULTS: Of the 1,769 of those who completed the survey, 1,225 reported a typed diagnosis of Ehlers-Danlos syndrome. Further stratification to the three most common types and reproductive-aged women (n=775) allowed conclusions to be made about differences in rates of obstetric complications and gynecologic dysfunction compared with the general population and between types of Ehlers-Danlos syndrome. Rates of obstetric outcomes for women who reported at least one pregnancy included term pregnancy in 69.7%, preterm birth in 25.2%, spontaneous abortion in 57.2%, and ectopic pregnancy in 5.1%. Infertility was reported by 44.1% of survey respondents. Normal menstrual cycles were reported by only 32.8% with intermenstrual bleeding occurring in 18.6%. Heavy menstrual bleeding was reported by 32.9% survey participants. Gynecologic pain reported included dysmenorrhea by 92.5% and dyspareunia by 77.0%. CONCLUSION: There is a much greater prevalence of obstetric and gynecologic issues reported by women with Ehlers-Danlos syndrome than in the general population. Additionally, rates differed significantly among the three most common types of Ehlers-Danlos syndrome with vascular type having the highest rates of adverse pregnancy outcomes and menstrual abnormalities. Physician providers should be aware of these challenges and should counsel patients with Ehlers-Danlos syndrome about relevant options and risks.

Molecular evaluation of proliferative-phase endometrium may provide insight about the underlying causes of infertility in women with endometriosis.

PURPOSE: To determine if endometrial gene expression is different in women with endometriosis-related infertility and fertile women. METHODS: Prospective study of mid-follicular phase endometrium in 47 subjects in two phases: microarray study of 10 infertile women with endometriosis and five fertile controls, and a quantitative real-time PCR (qRT-PCR) study of 27 infertile women with endometriosis and 15 fertile controls. Gene expression was determined by DNA microarray, and qRT-PCR used for 12 "promising" genes based on the microarray analysis. RESULTS: Compared to fertile controls, women with stage I-II endometriosis had 23, and women with stage III-IV had 35 genes that were significantly up- or down-regulated by microarray. However, using qRT-PCR, only chemokine ligand (CXCL) 13 was significantly down-regulated and somatostatin was significantly up-regulated with early endometriosis, and only CXCL 14 was significantly down-regulated with advanced endometriosis compared to fertile controls. CONCLUSIONS: Our findings indicate that the pattern of gene expression in proliferative-phase endometrium is different when comparing tissue from patients with endometriosis versus fertile controls. Recognition of these endometrial alterations could be helpful to diagnose and stage endometriosis, and may provide insight to explain why conception rates are low in women with endometriosis.

Association of blood type and patient characteristics with ovarian reserve.

OBJECTIVE: To assess whether blood type was associated with diminished ovarian reserve (DOR) (day-3 follicle-stimulating hormone level >10 IU/L), controlling for history of tobacco smoking, body mass index (BMI), history of endometriosis, ovarian surgery, previous pregnancy, and maternal age. DESIGN: Cross-sectional study. SETTING: Academic medical center, Division of Reproductive Endocrinology and Infertility. PATIENT(S): Women undergoing in vitro fertilization (IVF) from 2006-2011 (n = 305). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Presence of DOR in relation to a patient's blood type. RESULT(S): Other investigators have reported an increased risk for DOR in patients with blood type O and a protective effect on ovarian reserve for blood type A. We observed no association between a woman's blood type and DOR. We found an increased risk for DOR in patients aged 35 and older. Obesity (BMI ≥ 30 vs. BMI <25) was associated with lower odds of DOR. CONCLUSION(S): In comparison with blood type A, blood type O is not associated with an increase in DOR. We found no clinical implications for using blood type as a risk factor for DOR.

The effect of ketorolac on pregnancy rates when used immediately after oocyte retrieval.

OBJECTIVE: To study the effect of ketorolac, a potent anti-inflammatory medication, on in vitro fertilization (IVF) pregnancy outcomes when used at the time of oocyte retrieval. DESIGN: Retrospective review of 454 patients from 2003-2009. SETTING: Tertiary hospital-affiliated fertility center. PATIENT(S): Consecutive subfertile women undergoing their first IVF cycle. INTERVENTION(S): Ketorolac administration immediately after oocyte retrieval. MAIN OUTCOME MEASURE(S): Pregnancy, implantation, live-birth, and miscarriage rates, and postsurgical visual analog pain score. RESULT(S): Of the 454 patients undergoing their first IVF cycle for all indications, 103 received intravenous ketorolac immediately after oocyte retrieval, based on anesthesiologist preference. Patient and procedural characteristics were similar between both groups. The use of ketorolac had no effect on the rates of implantation, miscarriage, pregnancy, live birth, or multiple pregnancy. The patients receiving ketorolac experienced statistically significantly less pain. CONCLUSION(S): This study suggests ketorolac has no apparent detrimental effect on IVF pregnancy outcomes when administered immediately after oocyte retrieval. Ketorolac appears to be a safe and effective analgesic to use at the time of oocyte retrieval.

Ultrasound evaluation of uterine healing after laparoscopic intracapsular myomectomy: an observational study.

STUDY QUESTION: Can uterine scar healing after laparoscopic intracapsular myomectomy (LIM) be adequately monitored by traditional two-dimensional (2D) ultrasound (US) and Doppler velocimetry? SUMMARY ANSWER: The myometrial area of the scar after LIM can be followed by 2D US and Doppler velocimetry. WHAT IS KNOWN ALREADY: Apart from post-surgical adhesions, the main concern linked to laparoscopic myomectomy is the quality of healing of the myometrial incision: it has been suggested that US could be useful for assessing uterine scars after myomectomy. However, no diagnostic method has yet been widely accepted to assess the healing process. STUDY DESIGN, SIZE, DURATION: A cohort prospective study (level of evidence II-2), run in University-affiliated hospitals: 149 women with symptomatic uterine fibroids (UFs) underwent LIM, between January 2007 and October 2011. During follow up 13 patients withdrew from the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: After LIM, all patients were followed by traditional 2D US scanning and Doppler velocimetry on Days: 0, 1, 7, 30 and 45. Authors evaluated: number, size and location of UFs, scar diameter and Doppler velocimetry and resistance index (RI) of the uterine arteries, at their ascending branch. MAIN RESULTS AND THE ROLE OF CHANCE: The uterine examination showed a significant (P < 0.05) progressive reduction of uterine scar area from 78% of the previous UF location on the first day, to 19% on 30th day, and <4% on the 45th day. There was no correlation with the size of the fibroid or the relative reduction in the size of the scar, on both Days 1 and 45. There was a significant (P < 0.05) increase in the RI of the ipsilateral uterine arteries from 0.65 on the first post-operative day to 0.83 after 7 days followed by a decrease to 0.71 on the 30th and 0.61 on the 45th post-operative day. LIMITATIONS, REASONS FOR CAUTION: This is a cohort investigation on a limited number of patients and it does not surgically compare LIM and 'classic' myomectomy in the scar US follow up. WIDER IMPLICATIONS OF THE FINDINGS: LIM avoided intraoperative bleeding and excessive tissue damage, as post-operative US follow up showed, with just two intra-myometrial hematomas (1.5%). The 2D US and Doppler velocimetry, a non-invasive safe method to check the myometrium after LIM, can detect post-operative hematoma and disechogenic, heterogeneous or ill-defined scar area, all unfavorable signs for myometrial scarring. Moreover, Doppler transvaginal monitoring, evaluating the pulsatility index (PI) and RI of the uterine arteries at their ascending branch, could identify patients with altered PI and RI parameters, possible markers of impaired wound healing.

Cancer, fertility preservation, and future pregnancy: a comprehensive review.

Given the increases in 5-year cancer survival and recent advances in fertility preserving technologies, an increasing number of women with cancer are presenting for discussion of fertility preserving options. This review will summarize the risk of infertility secondary to cancer treatment, available treatment options for fertility preservation, and techniques to reduce future risks for patients. Concerns that will be addressed include the risk of the medications and procedures, the potential delay in cancer treatment, likelihood of pregnancy complications, as well as the impact of future pregnancy on the recurrence risk of cancer. Recent advances in oocyte cryopreservation and ovarian stimulation protocols will be discussed. Healthcare providers need to be informed of available treatment options including the risks, advantages, and disadvantages of fertility preserving options to properly counsel patients.