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.

Counseling and diagnostic evaluation for the infertile couple.

Educating couples about natural means to improve fertility should include a discussion about appropriate timing to initiate a diagnostic evaluation for infertility. Complete infertility testing for both male and female factors allows directed care for all abnormalities to optimize chances for conception.

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.

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.

Obstetric antiphospholipid syndrome: an update on pathophysiology and management.

Antiphospholipid antibodies (aPLs) are acquired antibodies directed against negatively charged phospholipids, a group of inner and outer cell membrane antigens found in mammals. Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings. Although obstetric APS was originally reported in association with slow progressive thrombosis and infarction in the placenta, it is most often associated with a poor obstetric outcome. In fact, obstetric APS is one of the most commonly identified causes of recurrent pregnancy loss (RPL). Thus obstetric APS is distinguished from APS in other organ systems where the most common manifestation is thrombosis. Several pathophysiological mechanisms of action of aPLs have been described. The most common histopathological finding in early pregnancy loss has been defective endovascular decidual trophoblastic invasion. Treatment with heparin and aspirin is emerging as the therapy of choice, with ∼75% of treated women with RPL and aPLs having a successful delivery compared with <50% without treatment. This review highlights the diagnostic challenges of obstetric APS, the obstetric complications associated with APS, proposed pathophysiological mechanisms of APS during pregnancy, and the management of women during and after pregnancy.

A short period of ejaculatory abstinence before intrauterine insemination is associated with higher pregnancy rates.

An ejaculatory abstinence period of

Novel clomiphene "stair-step" protocol reduces time to ovulation in women with polycystic ovarian syndrome.

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.

Absorption of vaginal estrogen cream during sexual intercourse: a prospective, randomized, controlled trial.

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.

Ultrasound-directed transvaginal myolysis: preclinical studies.

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.

The impact of uterine artery embolization on fertility and pregnancy outcome.

PURPOSE OF REVIEW: Uterine artery embolization for management of symptomatic fibroids is an effective and increasingly popular treatment option. There are several studies evaluating the effects of uterine artery embolization on later pregnancies; however, the effects on fertility are still largely uncertain. This paper reviews the current literature on the effects of this technique on fertility and pregnancy outcome. RECENT FINDINGS: Two recent studies have reported pregnancy rates following uterine artery embolization in women seeking pregnancy. A small, third study reported preliminary results in a randomized controlled trial comparing uterine artery embolization with myomectomy in women wishing to preserve fertility. SUMMARY: The body of medical literature supports use of uterine artery embolization as an effective treatment for symptoms of vaginal bleeding and pelvic pressure from uterine fibroids. Patient selection is critical in determining the appropriateness of this treatment option. Myomectomy remains the standard of care for women with symptomatic fibroids seeking fertility preservation.

Conservative management of placenta increta with selective arterial embolization preserves future fertility and results in a favorable outcome in subsequent pregnancies.

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.

Effect of progesterone supplementation in early pregnancy on the pregnancy outcome after in vitro fertilization.

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.

Effects of fibrin sealant on single-layer uterine incision closure in the New Zealand white rabbit.

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.

Uterine artery embolization as a treatment option for uterine myomas.

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.

Low-dose aspirin does not improve ovarian stimulation, endometrial response, or pregnancy rates for in vitro fertilization.

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.

Laparoscopic myomectomy for symptomatic uterine myomas.

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.