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Objective: The objective of the study was to determine the efficacy of a novel "stair-step" clomiphene protocol in women with polycystic ovarian syndrome (PCOS) who do not respond to 50 mg clomiphene. Study Design: This was a retrospective analysis at an academic fertility center. The stair-step protocol is performed as follows: 50 mg clomiphene for 5 days, ultrasonography on days 11-14. If unresponsive, immediately begin 100 mg clomiphene for 5 days and repeat ultrasound in 1 week. If still unresponsive, begin 150 mg clomiphene for 5 days and repeat the ultrasound in 1 week. Stair-step cycles were compared with published historical clomiphene outcomes for women who were nonresponsive. Results: The time to ovulation was 32-53 days less with the stair-step protocol compared with a traditional regimen. The dose-dependent ovulation rate was 64% at 100 mg with the stair-step protocol compared with 22% with a traditional regimen. Conclusion: It is not necessary to induce menses before increasing clomiphene doses in nonresponsive PCOS patients. [ABSTRACT FROM AUTHOR]

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., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (Copyright © 2021. Published by Elsevier Inc.)

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., Competing Interests: Financial Disclosure Paul B. Marshburn, M.D. disclosed being the inventor of U.S. patent No. 10,182,877 granted on January 22, 2019, covering the Total Capture Drape design and use. He reported no funding or financial gain from the patented drape. Paul B. Marshburn disclosed a payment for consulting from Cardinal Health. Brittany L. Anderson-Montoya disclosed receiving funding from the Society for Simulation in Healthcare for Associate Editor duties for the Journal and Mission Health for a guest speaker lecture. Leslie Hansen-Lindner reports receiving funding for expert testimony. The other authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

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., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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.

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.

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.

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., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Authors investigated 75 patients with uterine myomas, appraising whether fibroid pseudocapsule (FP) thickness varies depending on fibroid location, by a prospective cohort trial (level of evidence II-2) settled in University-affiliated Hospitals. Uteri were scanned via bidimensional and power Doppler ultrasound (US) to map the fibroids and record the FP thickness, prior to hysterectomy for symptomatic uterine fibroids. After hysterectomy, FP specimens were sampled and analyzed by pathologists. Ultrasound and histology data were matched. Pseudocapsule thickness of 108 fibroids was measured: subserosal fibroids (SSFs), intramural fibroids (IMFs), and fibroids near the endometrial cavity (FEC). The FEC's pseudocapsules were considerably thicker than those of IMF and SSF measured by US and histology (P = .001). A clear cutoff existed between FEC pseudocapsule thickness and all other pseudocapsules, with significant differences observed at 2 mm (P = .001). Similarity between histological and US measurements was observed only with IMF pseudocapsules, whereas FEC or SSF showed significant differences. The pseudocapsule of fibroids is considerably thicker near the endometrial cavity when compared to those of both IMFs and SSFs. Since fibroids closest to the endometrial cavity are the most involved in fertility and infertility and FP is considerably thicker near the endometrial cavity, it is possible to hypothesize an involvement of FP of fibroid near the endometrium since FP contains many neuropeptides and neurotransmitters that are physiologically active, even if these data may take on a broader meaning in a study on a larger number of patients., (© The Author(s) 2014.)

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.

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.

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., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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.

Objective: To describe a comprehensive approach to women with severe Asherman syndrome and amenorrhea, including preoperative, operative, and postoperative care and subsequent resumption menses, and pregnancy., Design: Retrospective case series., Setting: Tertiary care teaching hospital., Patient(s): Twelve women with severe Asherman syndrome and amenorrhea., Intervention(s): Preoperative administration of prolonged preoperative and postoperative oral E(2) to enhance endometrial proliferation, intraoperative abdominal ultrasound-directed hysteroscopic lysis of uterine synechia to ensure that the dissection is performed in the proper tissue plane, placement of a triangular uterine balloon catheter during surgery, and postoperative removal with placement of a copper intrauterine device (IUD) to maintain separation of the cavity and mechanically lyse newly formed adhesions during removal., Main Outcome Measure(s): Resumption of menses, pregnancy, and delivery., Result(s): All women resumed menses, although 5 of 12 had a preoperative maximal endometrial thickness of 4 mm or less, with follow-up ranging from 6 months to 10 years. Six of nine women less than age 39 years (67%) became pregnant, and four of six achieved a term or near-term delivery., Conclusion(s): Comprehensive management provides the best possible outcomes in poor-prognosis women with severe Asherman syndrome., (Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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.

The uterine fibroid pseudocapsule is a fibro-neurovascular structure surrounding a leiomyoma, separating it from normal peripheral myometrium. The fibroid pseudocapsule is composed of a neurovascular network rich in neurofibers similar to the neurovascular bundle surrounding a prostate. The nerve-sparing radical prostatectomy has several intriguing parallels to myomectomy. It may serve either as a useful model in modern fibroid surgical removal, or it may accelerate our understanding of the role of the fibrovascular bundle and neurotransmitters in the healing and restoration of reproductive potential after intracapsular myomectomy. Surgical innovations, such as laparoscopic or robotic myomectomy applied to the intracapsular technique with magnification of the fibroid pseudocapsule surrounding a leiomyoma, originated from the radical prostatectomy method that highlighted a careful dissection of the neurovascular bundle to preserve sexual functioning after prostatectomy. Gentle uterine leiomyoma detachment from the pseudocapsule neurovascular bundle has allowed a reduction in uterine bleeding and uterine musculature trauma with sparing of the pseudocapsule neuropeptide fibers. This technique has had a favorable impact on functionality in reproduction and has improved fertility outcomes. Further research should determine the role of the myoma pseudocapsule neurovascular bundle in the formation, growth, and pathophysiological consequences of fibroids, including pain, infertility, and reproductive outcomes.

The myoma pseudocapsule is a surgical-anatomical entity surrounding the fibroid that separates the myoma from normal uterine tissue. The myoma pseudocapsule has a delicate vascular network rich with neurotransmitters analogous to the neurovascular bundle surrounding the prostate. The pseudocapsule neurovascular bundle is extremely important during myomectomy to promote uterine myometrial healing and, consequently, for uterine reproductive function. New advancements in surgery, including the use of laparoscopic myomectomy by an intracapsular technique and magnification of the myoma pseudocapsule to enhance visualization are comparable to the dissection during a radical prostatectomy. Fibroid detachment occurring inside the pseudocapsule causes less bleeding, spares the neurovascular bundle and promotes better uterine healing. The maintenance of myometrial integrity after laparoscopic myomectomy maintains uterine function and therefore improves reproductive outcomes, including labor.

An ejaculatory abstinence period of

Objective: To determine if intercourse changed serum estradiol levels in women using vaginal E2 cream or in their male partners., Study Design: Prospective, randomized, placebo-controlled, crossover, blinded study of 10 postmenopausal women and their male sexual partners. Subjects were randomized to estradiol or placebo cream and intercourse, then crossed over after 7-14 days. Seven to 14 days later, the woman used vaginal estradiol cream and abstained from intercourse. Serum E2 levels were obtained 10-12 hours after each exposure., Results: Serum E2 levels were higher in 8 of 10 men after intercourse with vaginal estradiol cream, and this resulted in a small but significant (p = 0.03) increase in the estradiol levels as compared to placebo. Paradoxically, intercourse resulted in markedly lower estradiol levels in women as compared to abstinence (p = 0.004)., Conclusion: Men absorb vaginal estradiol during intercourse, whereas intercourse reduces estradiol absorption in women. Although serum estradiol levels were only mildly elevated in men, it is possible that long-term exposure could cause feminizing changes. In women, estradiol levels were markedly reduced by intercourse.

The ultimate goal is to develop a safe vaginal ultrasound-directed myolysis needle to treat uterine myomas. The specific preclinical study objective was to determine the optimal power to coagulate myomas in hysterectomy specimens with a prototype needle in a prospective preclinical study with an echogenic insulated needle electrode. In phase I of the study, myolysis was performed with ultrasound guidance at various powers and times. In phase II, a 20-W coagulating current was applied at defined distances from the serosa and surface temperatures measured. Myolysis with 10 to 20 W applied 5 to 10 seconds was optimal, because tissue popping occurred at 30 W or more when the needle was 5 mm or less from the serosa. The serosal temperature was never elevated above physiological ranges at any distance at this setting. Ultrasound-directed transvaginal myolysis may provide another option for women with uterine myomas if it is proven safe and effective in future clinical studies. On the basis of the observations in these preclinical studies, myolysis with 20 W for 10 seconds should be a safe parameter for clinical research, because there is no increased serosal temperature at these settings.

Objective: To present a case of selective arterial embolization for the treatment of placenta increta in a patient with subsequent pregnancy., Design: Case report and literature review., Setting: Community-based hospital., Patient(s): A 31-year-old G2P1 woman with placenta increta presenting with delayed postpartum hemorrhage., Intervention(s): Selective uterine artery embolization., Main Outcome Measure(s): Cessation of uterine hemorrhage, future pregnancy., Result(s): The patient's uterine bleeding immediately resolved. She subsequently delivered a healthy neonate at term without recurrence of abnormal placentation., Conclusion(s): Arterial embolization is effective for treating placenta increta in women who wish to preserve fertility. A review of the literature demonstrates a 76.9% success rate and an 11% complication rate.

A retrospective cohort study was performed to evaluate IVF clinical pregnancy rates and livebirth rates between patients receiving progesterone supplementation through the first trimester of pregnancy (first trimester protocol) at 12 weeks vs. discontinuation after a positive beta-hCG test 2 weeks after retrieval (luteal protocol) at 4 weeks of pregnancy. A similar rate of clinical pregnancies occurred at 7 weeks (81.8% luteal protocol vs. 85.8% first trimester protocol; P=.49) and for livebirth rates (76.8% luteal protocol vs. 75.0% first trimester protocol; P=.80), but a trend toward a higher rate of pregnancy loss after 7 weeks in the first trimester protocol group occurred (15.5% vs. 4.4%; P=.06), indicating that first trimester progesterone supplementation may support early pregnancy through 7 weeks by delaying miscarriage but does not improve livebirth rates.

Objective: To determine if the addition of fibrin sealant to incision closure in a rabbit uterine horn myomectomy model affects adhesion formation or strength of incision closure., Design: Prospective randomized controlled trial., Setting: Academic research center., Animal(s): New Zealand white female rabbits., Intervention(s): A pilot study revealed that the time interval for maximal uterine incision healing was eight weeks. Thirty New Zealand white rabbits underwent a 1-cm standardized myotomy incision on both uterine horns. A single interrupted stitch of 3-0 polygalactin suture was placed to reapproximate each incision. Fibrin sealant was then applied to one of each rabbit's horns (randomized). After eight weeks, the rabbits were killed, and the strength of myotomy closure was determined by measurement of maximal burst pressure for each uterine horn. Adhesion presence was recorded., Main Outcome Measure(s): Uterine burst pressure, adhesion presence., Result(s): The mean burst pressure was 267.8 (+/-75.8) mm Hg in the suture only group and 247.8 (+/-92.3) mm Hg in the suture and fibrin sealant group. There was no statistical difference in the presence of adhesions., Conclusion(s): Fibrin sealant did not strengthen myotomy repair nor did it reduce postoperative adhesion formation. There is no apparent advantage to fibrin sealant in this myomectomy model.

Information is still being collected on the long-term clinical responses and appropriate patient selection for UAE. Prospective RCTs have not been performed to compare the clinical results from UAE with more conventional therapies for symptomatic uterine leiomyomata. At least three attempts at conducting such RCTs have been unsuccessful because of poor patient accrual that related to differing patient expectation and desires, clinical bias, insurance coverage, and the tendency that patients who have exhausted other treatment options may be disposed more favorably to less invasive treatments. Other comparative studies have serious limitations. For example, the retrospective study that compared outcomes after abdominal myomectomy with UAE suggested that patients who received UAE were more likely to require further invasive treatment by 3 years than were recipients of myomectomy. Lack of randomization introduced a selection bias because women in the group that underwent UAEwere older and were more likely to have had previous surgeries. A prospective study of "contemporaneous cohorts," which excluded patients who had sub-mucosal and pedunculated subserosal myomas, sought to compare quality of life measures and adverse events in patients who underwent UAE or hysterectomy. The investigators concluded that both treatments resulted in marked improvement in symptoms and quality of life scores, but complications were higher in the group that underwent hysterectomy over 1 year. In this study,however, a greater proportion of patients who underwent hysterectomy had improved pelvic pain scores. Furthermore, hysterectomy eliminates uterine bleeding and the risk for recurrence of myomas. Despite the lack of controlled studies that compared UAE with conventional surgery, and despite limited extended outcome data, UAE has gained rapid acceptance, primarily because the procedure preserves the uterus, is less invasive, and has less short-term morbidity than do most surgical options. The cost of UAE varies by region, but is comparable to the charges for hysterectomy and is less expensive than abdominal myomectomy. The evaluation before UAE may entail additional fees for diagnostic testing, such as MRI, to assess the uterine size and screen for adenomyosis. Other centers have recommended pretreatment ultrasonography, laparoscopy, hysteroscopy, endometrial biopsy, and biopsy of large fibroids to evaluate sarcoma. Generally,after UAE the recovery time and time lost from work are less; however, the potential need for subsequent surgery may be greater when compared with abdominal myomectomy. Any center that offers UAE should adhere to published clinical guidelines,maintain ongoing assessment of quality improvements measures, and observe strict criteria for obtaining procedural privileges. After McLucas advocated that gynecologists learn the skill to perform UAE for managing symptomatic myomas, the Society of Interventional Radiology responded with a precautionary commentary on the level of technical proficiency that is necessary to maintain optimum results from UAE. The complexity of pelvic arterial anatomy, the skill that is required to master modern coaxial microcatheters, and the hazards of significant patient radiation exposure were cited as reasons why sound training and demonstration of expertise be obtained before clinicians are credentialed to perform UAE.A collaboration between the gynecologist and the interventional radiologist is necessary to optimize the safety and efficacy of UAE. The primary candidates for this procedure include women who have symptomatic uterine fibroids who no longer desire fertility, but wish to avoid surgery or are poor surgical risks. The gynecologist is likely to be the primary initial consultant to patients who present with complaints of symptomatic myomas. Therefore, they must be familiar with the indications, exclusions, outcome expectations, and complications of UAE in their particular center. When hysterectomy is the only option, UAE should be considered. Appropriate diagnostic testing should aid in the exclusion of most, but not all, gynecologic cancers and pregnancy. Other contraindications include severe contrast medium allergy, renal insufficiency, and coagulopathy. MRI may be used to screen women before treatment in an attempt to detect those who have adenomyosis; patients should be aware that UAE is less effective in the presence of solitary or coexistent adenomyosis. Because some women may experience ovarian failure after UAE, additional studies to determine basal follicle-stimulating hormone and estradiol before and after the procedure may provide insight into UAE-induced follicle depletion.UAE is a unique new treatment for uterine myomas, and is no longer considered investigational for symptomatic uterine fibroids. There is international recognition that data are needed from RCTs that compare UAE with surgical alternatives. Current efforts to provide prospective objective assessment of treatment outcomes and complications after UAE will help to optimize patient selection and clinical guidelines. FIBROID should provide critical data for the assessment of safety and outcomes measures for women who receive UAE for symptomatic uterine myomas.

Laparoscopic myomectomy (LM) is an increasingly accepted method of treatment for symptomatic uterine leiomyomas. It affords patients a minimally invasive surgery compared to the more traditional abdominal approach. Studies have shown the benefits of decreased blood loss, shorter hospital stay and recovery period, as well as decreased postoperative pain and fever in comparison to abdominal myomectomy (AM). Even myomas larger than 5 cm can be laparoscopically resected safely in the hands of an experienced surgeon. To date, studies indicate a decreased adhesion rate with the laparoscopic approach compared to the abdominal procedure. The use of adhesion barriers may decrease this rate further. In infertile women with myomas, pregnancy and live-birth rates improve following LM, and appear to be comparable with those rates achieved following AM. The data regarding the risk of uterine rupture in pregnancy following LM is limited. However, small studies show safe outcomes when patients are managed with the same degree of caution one might employ with post-abdominal myomectomy patients. In performing LM, a precise and diligent technique should be exercised to ensure a secure, multilayer closure.

Progesterone receptor (PR) variant mRNAs in human endometrium could encode proteins with the potential to alter progesterone action in states of normal and abnormal endometrial development. We have assessed the expression levels of mRNA for the wild-type PR and splice variants of PR mRNA lacking exon 4 (del-4 PR), exon 6 (del-6 PR), exons 4 and 6 (del-4&6 PR), and part of exon 4 (del-p4 PR) or part of exon 6 (del-p6 PR) in the human endometrium throughout menstrual cycle development. Eighty-eight endometrial specimens (47 proliferative, 41 secretory) were collected from patients undergoing hysterectomy for benign gynaecologic causes. Measurements by RT-PCR indicated that mRNAs for wild-type PR, and splice variants del-4 PR, del-6 PR, del-4&6 PR, del-p6 PR, and a novel del-p4 PR were detected in all endometrial specimens throughout the menstrual cycle. Higher levels of wild-type PR and all PR variant mRNAs were found in the early and mid-proliferative endometrial phases than in secretory endometrium. The relative expression of mRNA for all PR variants compared to wild-type PR mRNA, however, did not change through all stages of endometrial development. We, therefore, found no evidence of differential co-expression of the PR variants compared with wild-type PR during normal menstrual development. Future studies will determine if the expression profile of PR variant mRNAs will be different in the endometrium of patients with infertility, recurrent pregnancy loss, or endometrial adenocarcinoma.

Background: The purpose of this study is to determine if low-dose aspirin improved ovarian stimulation, endometrial response, or IVF pregnancy rates in our program., Methods: Retrospective analysis of 316 consecutive IVF cycles from 1995 through 2001. Aspirin 80 mg daily was initiated at the start of luteal leuprolide in 72 cycles. The 244 controls received no aspirin during treatment., Results: The live birth rate in aspirin users was 29%, slightly lower compared to 41% in the no aspirin control group (p = 0.07). Implantation rates were 21% with aspirin and 30% in the control population (p = 0.01). There was no difference in the maximal endometrial thickness between aspirin and non-aspirin groups. The two groups were similar regarding age, gonadotropin ampules, embryos, number of embryos transferred, prior parity, diagnosis, use of intracytoplasmic sperm injection, and stimulation protocol., Conclusion: Low-dose aspirin was not beneficial to IVF patients in our program. Aspirin does not enhance endometrial thickness, augment the ovarian response, or improve pregnancy rates.

Objective: To compare the effects of oral contraceptive (OC) pill pretreatment in recombinant FSH/GnRH-antagonist versus recombinant FSH/GnRH-agonist stimulation in in vitro fertilization (IVF) patients, and to evaluate optimization of retrieval day., Design: Prospective, randomized, multicenter study., Setting: Private practice and university centers., Patient(s): Eighty patients undergoing IVF who met the appropriate inclusion criteria., Intervention(s): Four study centers recruited 80 patients. The OC regimen began on cycle days 2 to 4 and was discontinued on a Sunday after 14 to 28 days. The recombinant FSH regimen was begun on the following Friday. The GnRH-agonist group was treated with a long protocol; the GnRH-antagonist was initiated when the lead follicle reached 12 to 14 mm. When two follicles had reached 16 to 18 mm, hCG was administered., Main Outcome Measure(s): The primary outcome measures were the number of cumulus-oocyte complexes, day of the week for oocyte retrieval, and total dose and days of stimulation of recombinant FSH. Secondary efficacy variables included pregnancy and implantation rate; serum E(2) levels on stimulation day 1; serum E(2), P, and LH levels on the day of hCG administration; follicle size on day 6 and day of hCG administration; the total days of GnRH-analogue treatment; total days on OC; total days from end of OC to oocyte retrieval; and the cycle cancellation rate., Result(s): Patient outcomes were similar for the days of stimulation, total dose of gonadotropin used, two-pronuclei embryos, pregnancy (44.4% GnRH-antagonist vs. 45.0% GnRH-agonist, P=.86) and implantation rates (22.2% GnRH-antagonist vs. 26.4% GnRH-agonist, P=.71). Oral contraceptive cycle scheduling resulted in 78% and 90% of retrievals performed Monday through Friday for GnRH-antagonist and GnRH-agonist. A one day delay in OC discontinuation and recombinant FSH start would result in over 90% of oocyte retrievals occurring Monday through Friday in both groups., Conclusion(s): The OC pretreatment in recombinant FSH/GnRH-antagonist protocols provides a patient-friendly regimen and can be optimized for weekday retrievals. No difference was seen in number of 2PN embryos, cryopreserved embryos, embryos transferred, implantation and pregnancy rates between the two stimulation protocols.

Objective: To evaluate the safety, efficacy, and techniques of laparoscopic myomectomy as treatment for symptomatic uterine myomas., Design: Medline literature review and cross-reference of published data., Results: Results from randomized trials and clinical series have shown that laparoscopic myomectomy provides the advantages of shorter hospitalization, faster recovery, fewer adhesions, and less blood loss than abdominal myomectomy when performed by skilled surgeons. Improvements in surgical instruments and techniques allows for safe removal and multilayer myometrial repair of multiple large intramural myomas. Randomized trials support the use of absorbable adhesion barriers to reduce adhesions, but there is no apparent benefit of presurgical use of GnRH agonists. Pregnancy outcomes have been good, and the risk of uterine rupture is very low when the myometrium is repaired appropriately., Conclusion(s): Advances in surgical instruments and techniques are expanding the role of laparoscopic myomectomy in well-selected individuals. Meticulous repair of the myometrium is essential for women considering pregnancy after laparoscopic myomectomy to minimize the risk of uterine rupture. Laparoscopic myomectomy is an appropriate alternative to abdominal myomectomy, hysterectomy, and uterine artery embolization for some women.

Objective: To determine the optimal approach to prevent adhesions comparing leuprolide acetate (GnRH-a), Interceed (oxidized regenerated cellulose; Johnson & Johnson Medical, Inc., New Brunswick, NJ), and a combination of leuprolide with Interceed in a rabbit uterine horn adhesion model., Design: Prospective, randomized, blinded study., Setting: Certified animal care facility., Animal(s): Twenty-eight sexually mature, female New Zealand White rabbits., Intervention(s): Animals were prospectively randomized (by number generator) to receive GnRH-a or saline. After 6 weeks, standard surgical manipulations were performed at three sites in each uterine horn by [1]. suture, [2]. unipolar cautery, and [3]. superficial abrasion. Interceed was applied over one randomly assigned uterine horn only. Six weeks after surgery, uterine adhesions were assessed visually, and tissue fibrosis was assessed by histology., Main Outcome Measure(s): Presence or absence of adhesions and microscopic tissue fibrosis., Result(s): Gonadotropin-releasing hormone agonist significantly decreased adhesions, whereas Interceed alone did not reduce adhesions. However, GnRH agonist plus Interceed was the most effective measure to reduce tissue fibrosis., Conclusion(s): Preoperative GnRH-a is more effective than Interceed in preventing surgical adhesions in the rabbit uterine horn. However, preoperative GnRH-a plus Interceed may provide optimal results in this animal model, because microscopic tissue fibrosis is minimized with this combination.

Objective: To determine if a fixed-dose stimulation protocol with monitoring limited to a single ultrasound can provide acceptable outcomes in assisted reproduction technologies (ART) procedures in appropriately selected patients., Design: Prospective study of all minimally monitored ART cycles from 1996 through 1998., Setting: University ART program., Patients: Eligibility included Institutional Review Board consent, age 18-37, basal FSH < or = 10, normal semen parameters, and regular menses. IVF (n = 81) and GIFT (n = 14)., Interventions: A single ultrasound was performed after 8 or 9 days of stimulation in a fixed-schedule long luteal phase leuprolide protocol. No hormone levels were obtained. Human chorionic gonadotropin was administered when at least 2 follicles were projected to reach 18 mm., Main Outcome Measures: Pregnancy, delivery, and implantation rates., Results: The clinical pregnancy rates were 51% for IVF and 36% for GIFT. Delivery rates were 42% for IVF and 29% for GIFT. The implantation rates for IVF were 23% and 17% for GIFT. No patient was admitted for ovarian hyperstimulation., Conclusions: We were able to achieve satisfactory pregnancy and delivery rates in properly selected patients with a minimal monitoring protocol, limited to a single ultrasound near the end of a fixed-stimulation regimen. The reduced time commitment and cost led to a very high patient acceptance of this approach.

Objective: To determine if extended treatment with doxycycline before and after an in vitro fertilization (IVF) procedure can minimize the detrimental effect of a hydrosalpinx., Design: Retrospective analysis., Setting: University IVF program., Patient(s): Patients undergoing IVF, including 17 with a hydrosalpinx, 25 with adhesions or proximal tubal occlusion, and 22 with endometriosis or unexplained infertility., Intervention(s): Women with a documented hydrosalpinx were prescribed doxycycline 100 mg twice daily starting 1 week before expected retrieval and continued until 6 days after retrieval. No antibiotics were prescribed in the other groups., Main Outcome Measure(s): Implantation rates and IVF outcomes., Result(s): Implantation rates were 30% for the doxycycline-treated group of patients with a hydrosalpinx, 27% for the group with tubal occlusion/adhesion, and 24% for the group with endometriosis or unexplained infertility. Eight (47%) of 17 patients with a hydrosalpinx had a live birth, compared with 11 (44%) of 25 for the group with tubal occlusion/adhesion and 12 (55%) of 22 for the group with endometriosis/unexplained infertility. There were no differences between the groups in patient age, number of oocytes retrieved, fertilization rate, or number of blastomeres of the transferred embryos., Conclusion(s): No detrimental effect of a hydrosalpinx was evident for patients treated with extended doxycycline. Tremendous cost savings can be realized if treatment with 2 weeks of an inexpensive antibiotic provides outcomes comparable to surgical correction of a hydrosalpinx before IVF.