Hysteroscopic Management of Asherman's Syndrome.

In developed countries Asherman's syndrome is almost always the result of a prior intrauterine operative trauma. This is often asymptomatic but may result in hypo- or amenorrhea and can contribute to infertility and pregnancy complications. We review their etiology, clinical implications, and systems proposed to classify their extent. The numerous methods reported for performing lysis of intrauterine adhesions are summarized along with clinical results. Current strategies to prevent recurrence of intrauterine adhesions have not been conclusively shown to be clinically effective, but the potential for endometrial regeneration using stem cells is an exciting modality under investigation.

Azoospermia and embryo morphokinetics: testicular sperm-derived embryos exhibit delays in early cell cycle events and increased arrest prior to compaction.

PURPOSE: Sperm play an essential role in embryonic genome activation and embryonic progression to blastocyst. In the present work, we focus on development of embryos created as a result of ICSI with testicular or epididymal sperm from azoospermic males and compare this to outcomes from normospermic males. The objective of this study was to determine if sperm origin influences clinical outcomes, the kinetics of embryo development, or the incidence of cleavage anomalies and multinucleation. METHODS: A total of 93 consecutive intracytoplasmic sperm injection cycles (ICSI) performed for 83 couples were included in this study. Observations were made on 594 fertilized oocytes cultured in the EmbryoScope using time-lapse microscopy (TLM). Epididymal sperm (n = 29) cycles or surgically retrieved sperm from the testis (TESE; n = 37 cycles) of men with either obstructive (OA) or non-obstructive azoospermia (NOA) were used to inject oocytes. A further 27 ICSI cycles were performed using ejaculated sperm from normospermic males, designated as our control sperm (CS) group. Kinetic data and cycle outcomes were retrospectively analyzed. RESULTS: The clinical pregnancy rate was not different between the three groups (TESE 51.4%, PESA 57.7%, and CS 59.3%). A non-significant decrease was observed in both implantation (30.9%) and live birth rate (43%) with TESE as compared to PESA (35.3%, 58%, respectively) and CS groups (45.1%, 56%, respectively). Failure to compact was significantly higher amongst TESE-NOA embryos (35.2%; P < 0.001) as compared to TESE-OA (4%), PESA (9%), and CS (3.8%) embryos. The two points at which TESE-derived embryos (both NOA and OA) behaved most differently from PESA and CS embryos was at cc2 (t3-t2; time to initiation of the second cell cycle) and tSB (time to start of blastulation). A significantly lower percentage of TESE embryos exhibited kinetics typically ascribed to high quality embryos with the greatest developmental potential. Finally, the incidence of direct uneven cleavage (DUC) was observed to be significantly higher after ICSI with sperm retrieved from azoospermic males. CONCLUSIONS: TLM allowed a more in depth comparison of paternal influence on embryo morphokinetics and helped to identify specific differences in cell cycle kinetics. TESE-NOA embryos exhibited a higher incidence of compaction failure.

Effect of surgery on ovarian reserve in women with endometriomas, endometriosis and controls.

BACKGROUND: Many women who experience endometriosis and endometriomas also encounter problems with fertility. OBJECTIVE: The purpose of this study was to determine the impact of surgical excision of endometriosis and endometriomas compared with control subjects on ovarian reserve. STUDY DESIGN: This was a prospective cohort study of 116 women aged 18-43 years with pelvic pain and/or infertility who underwent surgical treatment of suspected endometriosis (n=58) or endometriomas (n=58). Based on surgical findings, the suspected endometriosis group was further separated into those with evidence of peritoneal disease (n=29) and those with no evidence of endometriosis (n=29). Ovarian reserve was measured by anti-Müllerian hormone and compared before surgery and at 1 month and 6 months after surgery. RESULTS: Baseline anti-Müllerian hormone values were significantly lower in the endometrioma vs negative laparoscopy group (1.8 ng/mL [95% confidence interval, 1.2-2.4 ng/mL] vs 3.2 ng/mL [95% confidence interval, 2.0-4.4 ng/mL]; P<.02), but the peritoneal endometriosis group was not significantly different than either of these groups. Only patients with endometriomas had a significant decline in ovarian reserve at 1 month (-48%; 95% confidence interval, -54 to -18%; P<.01; mean anti-Müllerian hormone baseline value, 1.77-1.12 ng/mL at 1 month). Six months after surgery, anti-Müllerian hormone values continued to be depressed from baseline but were no longer significantly different. The rate of anti-Müllerian hormone decline was correlated positively with baseline preoperative anti-Müllerian hormone values and the size of endometrioma that was removed. Those with bilateral endometriomas (n=19) had a significantly greater rate of decline (53.0% [95% confidence interval, 35.4-70.5%] vs 17.5% [95% confidence interval, 3.2-31.8%]; P=.002). CONCLUSION: At baseline, patients with endometriomas had significantly lower anti-Müllerian hormone values compared with women without endometriosis. Surgical excision of endometriomas appears to have temporary detrimental effects on ovarian reserve.

Women's preference of cosmetic results after gynecologic surgery.

STUDY OBJECTIVE: To determine the cosmetic appeal of different incision types used in gynecologic surgery. DESIGN: One hundred women between the ages of 20 and 40 years were shown 4 color photographs of a female abdomen with incision sites marked for Pfannenstiel, minilaparotomy, traditional laparoscopy, and robotic-assisted laparoscopy. The women were asked to rank the photographs on cosmetic appeal alone. An additional photograph depicting single-port laparoscopy was then added, and patients were asked to again rank the photographs. Participants were also asked basic demographic information and prior surgical history. SETTING: Office practice. PATIENTS: One hundred women between the ages of 20 and 40. INTERVENTION: Participants. MEASUREMENTS AND MAIN RESULTS: Minilaparotomy was ranked as the most appealing incision among the first set of photographs by 74% of the participants, and the remaining 26% preferred traditional laparoscopy. Robotic-assisted laparoscopy was ranked as the least appealing scar type by 42%, and no patient selected it as their first choice. Sixty-four percent preferred the appearance of a single-port laparoscopic scar when that option was added. The only demographic variable that reached statistical significance was the presence of prior abdominal surgery. Patients without prior surgery ranked minilaparotomy as more cosmetically appealing. CONCLUSIONS: When several minimally invasive surgical approaches are possible, the patient should be counseled regarding the cosmetic results of each. Patients in this study strongly preferred the appearance of minilaparotomy and single-port incisions over full Pfannenstiel or robotic incisions.

Laparoscopic transfundal approach to cervical dilation: a novel treatment for cervical stenosis and cervical factor infertility.

OBJECTIVE: To demonstrate a novel technique used to restore cervical patency in a patient with severe iatrogenic cervical stenosis. DESIGN: Surgical video case report. SETTING: A single academic institution. PATIENT(S): We highlight the case of a 35-year-old nulliparous woman with a history of primary infertility. Her past medical history was significant for focal, invasive, well-differentiated squamous cell carcinoma of the cervix, for which she underwent a loop electrosurgical excision procedure. During her infertility assessment, she was found to have an extremely stenotic cervix that was refractory to conventional treatment options. INTERVENTIONS: This video highlights our innovative laparoscopic transfundal technique used to restore her cervical patency. MAIN OUTCOME MEASURES: None, as this is a descriptive case report. RESULTS: Postoperatively, the patient had continued cervical patency for >1 year with successful fertility treatment resulting in pregnancy. CONCLUSIONS: To our knowledge, this is the first case report describing a laparoscopic transfundal approach used to reestablish cervical patency. This approach may be considered for patients with cervical stenosis who have not responded to standard conservative therapies.

The new Rapid-i carrier is an effective system for human embryo vitrification at both the blastocyst and cleavage stage.

BACKGROUND: The Rapid-i is a new FDA cleared closed carrier for embryo vitrification. The cooling rate of - 1220°C/min is far lower than that reported with open vitrification systems such as the cryoloop (-15,000°C/min). Little published data is currently available on this device. This study presents our initial clinical data, as well as live birth outcomes, with the Rapid-i. The efficacy of this device for the cryopreservation of cleavage, as well as blastocyst stage human embryos is also analyzed. We further compare outcomes to those achieved with the cryoloop, an "open" vitrification system routinely used in our laboratory. METHODS: Human embryos were vitrified at either the 8-10 cell stage or else the blastocyst stage. The vitrification protocol was: 7.5% DMSO/7.5% ethylene glycol (EG) (2-3 min) followed by incubation in 15% DMSO /15% EG (45 sec) before loading on the vitrification carrier. Cryoprotectant was removed during warming by sequential washes in 0.25 M and 0.125 M sucrose in culture medium. Clinical outcome data for frozen cycles between January 2011 and August 2012 were stratified according to carrier and cell stage. The student t-test and chi square test were used to compare results. P value of < 0.05 was considered significant. RESULTS: A total of 486 vitrified-warmed embryos were assessed and 92% of them were transferred. The clinical pregnancy rate (CPR) and implantation rate (IR) with Rapid-i vitrified blastocysts were 59% and 49%, versus 47% and 37%, respectively for cleavage stage embryos. This was not statistically different from results with the cryoloop vitrified blastocysts (CPR 46%, IR 38%) nor the cleavage stage vitrified embryos (CPR 49%, IR 35%). To date, there have been 31 deliveries of 34 healthy infants from Rapid-i vitrified embryos, with another 12 pregnancies still on-going. CONCLUSIONS: The Rapid-i offers an excellent alternative to existing open vitrification devices for embryo cryopreservation at the 8-10 cell stage as well as the blastocyst stage. Use of this type of "closed" sealed system that prevents direct contact between the embryos and liquid nitrogen reduces the potential risk of sample cross-contamination or infection. These preliminary data and live birth outcomes have paved the way toward transitioning to a closed vitrification system in our own IVF program.

Effect of follicular fluid oxidative stress parameters on intracytoplasmic sperm injection outcome.

OBJECTIVE: The purpose of this study was to evaluate the association between the follicular fluid (FF) reactive oxygen species (ROS) levels, total antioxidant capacity (TAC) and ROS-TAC score and pregnancy after intracytoplasmic sperm injection (ICSI). METHODS: A total of 138 consecutive women who had ICSI were included in this study. FF ROS and TAC were measured by enhanced chemiluminescence and colorimetric assay, respectively, and then the ROS-TAC score was calculated. RESULTS: Out of the 138 included patients, 42 (30%) achieved pregnancy after ICSI. Log ROS, TAC, and the ROS-TAC score were not significantly different across diagnoses. Pregnant cycles were associated with significantly lower ROS (P < 0.001), higher TAC (P < 0.001) and higher ROS-TAC scores (P < 0.001). After adjusting for age, there was a significant positive correlation between log ROS and the number of follicles on the day of HCG administration (correlation 0.20, 95% CI: 0.02, 0.39) as well as the number of oocytes retrieved (correlation 0.18, 0.001, 0.36) but not with TAC. Interestingly, in women with endometriosis, higher TAC levels and higher ROS-TAC scores were associated with a higher likelihood of finding normal oocytes (P = 0.005 and P = 0.002, respectively). CONCLUSION: Higher FF TAC, higher FF ROS-TAC scores and lower FF ROS levels are associated with pregnancy after ICSI. Oxidative stress parameters may be markers of metabolic activity within the follicle.

A review of the pathophysiology of recurrent implantation failure.

Implantation is a critical step in human reproduction. The success of this step is dependent on a competent blastocyst, receptive endometrium, and successful cross talk between the embryonic and maternal interfaces. Recurrent implantation failure is the lack of implantation after the transfer of several embryo transfers. As the success of in vitro fertilization has increased and failures have become more unacceptable for patients and providers, the literature on recurrent implantation failure has increased. While this clinical phenomenon is often encountered, there is not a universally agreed-on definition-something addressed in an earlier portion of this Views and Reviews. Implantation failure can result from several different factors. In this review, we discuss factors including the maternal immune system, genetics of the embryo and parents, anatomic factors, hematologic factors, reproductive tract microbiome, and endocrine milieu, which factors into embryo and endometrial synchrony. These potential causes are at various stages of research and not all have clear implications or immediately apparent treatment.

Randomized study of G-TL and global media for blastocyst culture in the EmbryoScope: morphokinetics, pregnancy, and live births after single-embryo transfer.

OBJECTIVE: To evaluate the efficacy of two different in vitro fertilization culture media for blastocyst development, pregnancy, and live birth rate. Global (GB) medium (used without refreshment) and G-TL medium (designed specifically for culture in time-lapse incubators) were compared. DESIGN: Prospective randomized study of sibling embryo culture in two culture media. SETTING: In vitro fertilization clinic. PATIENT(S): Women undergoing fresh or frozen cycles using autologous or donor oocytes. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The primary endpoints were implantation, pregnancy, and live birth rate (LBR) after single blastocyst transfer. Secondary endpoints included embryo morphokinetics, development of good-quality blastocysts, and euploidy rate. RESULT(S): Kinetic data from 10,768 sibling pronucleate embryos cultured in the EmbryoScope were compared. GB embryos initiated compaction earlier and formed morula sooner than their G-TL counterparts. The mean timing for start of blastulation did not differ. The interval between start of blastulation and time of blastocyst formation was observed to be <12 hours for proportionately more GB compared with G-TL-cultured embryos. Despite a higher rate of observed dysmorphisms in GB embryos, the euploidy rate among biopsied blastocysts did not differ between media. A total of 820 single-embryo transfer cycles were performed. Implantation rates were similar between media, independent of whether the embryo transferred was fresh (GB 58.7% vs. G-TL 61.7%) or frozen (GB 64.1% vs. G-TL 60.5%). Live birth rates were also not different. With GB medium, the LBR for fresh and frozen transfers was 54.2% and 53.1%, respectively, as compared with 51.1% and 50%, respectively, with G-TL. CONCLUSION(S): Uninterrupted culture in a time-lapse incubator without medium refreshment was well supported by both media tested. Differences in morphokinetics did not necessarily dictate the superiority of one media over the other. Both pregnancy and LBR were not significantly influenced by choice of culture medium. The euploidy rate was also independent of culture medium.

Current controversies in tubal disease, endometriosis, and pelvic adhesion.

Reproductive surgery for proximal and distal tubal occlusion, as well as for reversal of tubal ligation, may be an alternative or an adjunct to IVF. Surgery for adenomyosis and endometriosis, including endometriomas, may be considered for the treatment of infertility and/or pelvic pain but carries the risks of surgical complications and diminished ovarian reserve. A greater understanding of the pathogenesis of postoperative peritoneal adhesion formation is needed to develop more effective preventive measures to optimize the clinical results of surgery.

Does laparoscopic ileal pouch-anal anastomosis reduce infertility compared with open approach?

BACKGROUND: The aim of this study was to assess the association of the mode of surgery on female fertility after restorative proctocolectomy with ileal pouch-anal anastomosis. METHODS: All female patients aged 18 to 44 years who underwent restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis, familial adenomatous polyposis, or Crohn's disease at the Cleveland Clinic Ohio or the Cleveland Clinic Florida from 1983 to 2012 were sent a standardized fertility questionnaire. Infertility was defined as lack of pregnancy after 1 year of unprotected sexual intercourse. Patients who had attempted to conceive after restorative proctocolectomy with ileal pouch-anal anastomosis were compared based on the surgical approach: laparoscopic ileal pouch-anal anastomosis versus open ileal pouch-anal anastomosis. RESULTS: A total of 890 female patients were surveyed, of which 519 (58.3%) responded. Of these, 161 (31%) had attempted pregnancy after surgery: 18 (12%) had laparoscopic ileal pouch-anal anastomosis and 143 (88%) had open ileal pouch-anal anastomosis. There were no significant differences regarding demographics between groups. There was no difference in reported infertility rates (61.1% vs 65%, respectively, P = 0.69) between the laparoscopic ileal pouch-anal anastomosis and open ileal pouch-anal anastomosis groups. The median time to pregnancy (3.5 months vs 9 months, respectively, log-rank P = 0.01) was reduced in patients who underwent laparoscopic ileal pouch-anal anastomosis compared with those who underwent open ileal pouch-anal anastomosis. CONCLUSION: Postoperative infertility rates were higher after ileal pouch-anal anastomosis regardless of mode of surgery. However, laparoscopy was associated with a significantly reduced time to conceive compared with the open approach.

Restoration of fertility after hysteroscopic removal of intrauterine bone fragments.

BACKGROUND: The presence of intrauterine bone fragments is rare. They may prevent pregnancy by an intrauterine device-like effect. Hysteroscopy is required for definitive diagnosis and treatment. CASE: A woman experienced secondary infertility after a dilatation and evacuation at 22 weeks of gestation. She subsequently conceived spontaneously shortly after hysteroscopic removal of numerous intrauterine bone fragments. CONCLUSION: Intrauterine bone fragments may result from retained fetal bones or osseous metaplasia or both. These bone fragments may contribute to infertility, as evidenced by the restoration of fertility after hysteroscopic removal.

Topical hemostatic agents in gynecologic surgery.

Biosurgical compounds and pharmacologic agents can serve as surgical adjuncts to prevent or curtail intraoperative bleeding. Medline, PubMed, and Cochrane electronic data bases were used to search the English literature from 1966 to March 2007 using the terms topical, hemostatic agents, and gynecologic surgery. Several effective topical hemostatic agents are available to reduce intraoperative blood loss. Data on their application in gynecologic surgery are limited, and guidelines for selecting one over another for specific indications are lacking.

Association between time from endometriosis surgery and outcome of in vitro fertilization cycles.

OBJECTIVE: To evaluate the effect of time from surgery on the outcome of subsequent in vitro fertilization (IVF) cycles in endometriosis patients. STUDY DESIGN: One hundred five women treated surgically for endometriosis and who underwent 252 IVF cycles were included. Approximately 1/2, 1/4 and 1/5 of the study group underwent 1, 2 and 3 cycles, respectively. We used the cycle as the basic unit of analysis with the time since surgery as the independent variable and the clinical pregnancy as the dependant variable. We used nonparametric approach for estimating the probabilities. To convey the uncertainty of the probability estimates, we produced bootstrap 95% CI. RESULTS: The overall pregnancy rate was 31%. There does not appear to be any relationship between the length of time from surgery and clinical outcome. The point estimates suggest that there may be a slight negative relationship, since the estimated probability decreases steadily from 0.34 to 0.21 as the time since surgery goes from 0.5 to 5 years. CONCLUSION: The data do not provide evidence for a strong relationship between the time since surgery and the probability of a clinical pregnancy with IVF.

Are cleavage anomalies, multinucleation, or specific cell cycle kinetics observed with time-lapse imaging predictive of embryo developmental capacity or ploidy?

OBJECTIVE: To determine whether cleavage anomalies, multinucleation, and specific cellular kinetic parameters available from time-lapse imaging are predictive of developmental capacity or blastocyst chromosomal status. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Single academic center. PATIENT(S): A total of 1,478 zygotes from patients with blastocysts biopsied for preimplantation genetic screening were cultured in the EmbryoScope. INTERVENTION(S): Trophectoderm biopsy. MAIN OUTCOME MEASURE(S): Embryo dysmorphisms, developmental kinetics, and euploidy. RESULT(S): Of the 767 biopsied blastocysts, 41.6% (95% confidence interval [CI], 38%-45%) were diagnosed as euploid. Individual dysmorphisms such as multinucleation, reverse cleavage, irregular chaotic division, or direct uneven cleavage were not associated with aneuploidy. Direct uneven cleavage and irregular chaotic division embryos did, however, exhibit lower developmental potential. The presence of two or more dysmorphisms was associated with an overall lower euploidy rate, 27.6% (95% CI 19%-39%). Early embryo kinetics were predictive of blastocyst development but not ploidy status. In contrast, chromosomal status correlated significantly with start time of blastulation (tSB), expansion (tEB), and the tEB-tSB interval. A lower euploidy rate, 36.6% (95% CI 33%-42%) was observed with tSB ≥ 96.2 hours, compared with 48.2% with tSB < 96.2 (95% CI 42%-54%). A drop in euploidy rate to 30% (95% CI 25%-37%) was observed in blastocysts with delayed expansion (tEB > 116). The proportion of euploid blastocysts was increased with tEB-tSB intervals of ≤13 hours. A logistic regression model to enhance the probability of selecting a euploid blastocyst was constructed. CONCLUSION(S): Morphokinetics may aid in selection of euploid embryos from a cohort of day 5/6 blastocysts.

Tubal anastomosis by robotic compared with outpatient minilaparotomy.

OBJECTIVE: To compare tubal anastomosis by robotic system compared with outpatient minilaparotomy. METHODS: In this retrospective case-control study, women were identified by current procedural terminology code for tubal anastomosis. We included all cases of tubal anastomosis for reversal of a prior tubal ligation by either outpatient minilaparotomy or robotic system technique. Cases performed by laparoscopy without aid of the robot were excluded. Comparisons were based on Fisher's exact, chi(2), and Wilcoxon rank sum tests. RESULTS: There were 26 cases of tubal anastomosis performed with the robot and 41 cases performed by outpatient minilaparotomy. The two groups were comparable in age, body mass index, and parity. Anesthesia time for the robotic technique (median with interquartile range) was 283 (267-290) minutes compared with 205 (170-230) minutes with outpatient minilaparotomy (P<.001). Surgical times for the robot and minilaparotomy were 229 (205-252) minutes and 181 (154-202) minutes respectively (P=.001). Hospitalization times, pregnancy, and ectopic pregnancy rates were not significantly different. The robotic technique was more costly. The median difference in costs of the procedures was $1,446 (95% confidence interval $1,112-1,812) (P<.001). The time to return to work was significantly shorter in the robotic system group by approximately 1 week (P=.013). CONCLUSION: Robotic surgery for tubal anastomosis was successfully accomplished without conversion to laparotomy. The robotic technique for tubal anastomosis required significantly prolonged surgical and anesthesia times over outpatient minilaparotomy (P

Recurrent umbilical endometriosis after laparoscopic treatment of minimal pelvic endometriosis: a case report.

BACKGROUND: Umbilical endometriosis is extremely rare. The majority of cases occur spontaneously. There have been a few reported cases following laparoscopy but none for the treatment of pelvic endometriosis. CASE: Umbilical endometriosis occurred 20 months after laparoscopic treatment of stage 1 pelvic endometriosis. The symptoms recurred 7 months following excision of the lesion and were successfully treated with silver nitrate cautery. CONCLUSION: This is the first reported case of umbilical endometriosis following laparoscopic treatment of pelvic endometriosis as well as the first to demonstrate that chemical cautery may cure small lesions.

In vitro fertilization update.

Success rates with in vitro fertilization (IVF) continue to improve as we gain insight into optimal culture conditions for gametes and embryos. New procedures such as in vitro egg maturation, preimplantation genetic testing, single embryo transfer, and oocyte freezing hold the promise of reducing the cost, inconvenience, and risks of IVF, as well as preserving future fertility. We provide an overview of the current and experimental assisted reproductive technology techniques.

Extrapelvic Endometriosis.

Extrapelvic endometriosis is a rare and complex phenomenon. The pathologic mechanism of intrapelvic endometriosis is generally accepted as being largely due to retrograde menstruation through the fallopian tubes; however, the mechanism by which extrapelvic endometriosis forms has proven to be much more elusive. This article reviews the pathophysiology, clinical signs and symptoms, diagnostic techniques, and treatment recommendations for extrapelvic endometriosis of the umbilicus, abdominal wall, thorax, and vulva.