L.R. Goodman

Analysis of embryo morphokinetics, multinucleation and cleavage anomalies using continuous time-lapse monitoring in blastocyst transfer cycles

BackgroundTime-lapse imaging combined with embryo morphokinetics may offer a non-invasive means for improving embryo selection. Data from clinics worldwide are necessary to compare and ultimately develop embryo classifications models using kinetic data. The primary objective of this study was to determine if there were kinetic differences between embryos with limited potential and those more often associated with in vitro blastocyst formation and/or implantation. We also wanted to compare putative kinetic markers for embryo selection as proposed by other laboratories to what we were observing in our own laboratory setting.MethodsKinetic data and cycle outcomes were retrospectively analyzed in patients age 39 and younger with 7 or more zygotes cultured in the Embryoscope. Timing of specific events from the point of insemination were determined using time-lapse (TL) imaging. The following kinetic markers were assessed: time to syngamy (tPNf), t2, time to two cells (c), 3c (t3), 4c ( t4), 5c (t5), 8c (t8), morula (tMor), start of blastulation (tSB); tBL, blastocyst (tBL); expanded blastocyst (tEBL). Durations of the second (cc2) and third (cc3) cell cycles, the t5-t2 interval as well as time to complete synchronous divisions s1, s2 and s3 were calculated. Incidence and impact on development of nuclear and cleavage anomalies were also assessed.ResultsA total of 648 embryos transferred on day 5 were analyzed. The clinical pregnancy and implantation rate were 72% and 50%, respectively. Morphokinetic data showed that tPNf, t2,t4, t8, s1, s2,s3 and cc2 were significantly different in embryos forming blastocysts (ET or frozen) versus those with limited potential either failing to blastulate or else forming poor quality blastocysts ,ultimately discarded. Comparison of embryo kinetics in cycles with all embryos implanting (KID+) versus no implantation (KID-) suggested that markers of embryo competence to implant may be different from ability to form a blastocyst. The incidence of multinucleation and reverse cleavage amongst the embryos observed was 25% and 7%, respectively. Over 40% of embryos exhibiting these characteristics did however form blastocysts meeting our criteria for freezing.ConclusionsThese data provide us with a platform with which to potentially enhance embryo selection for transfer.

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.

Delayed blastulation, multinucleation, and expansion grade are independently associated with live-birth rates in frozen blastocyst transfer cycles

OBJECTIVE To identify blastocyst features independently predictive of successful pregnancy and live births with vitrified-warmed blastocysts. DESIGN Retrospective study. SETTING Academic hospital. PATIENT(S) Women undergoing a cycle with transfer of blastocysts vitrified using the Rapid-i closed carrier (n = 358). INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Clinical pregnancy and live-birth rates analyzed using logistic regression analysis. RESULT(S) A total of 669 vitrified-warmed blastocysts were assessed. The survival rate was 95%. A mean of 1.7 ± 0.5 embryos were transferred. The clinical pregnancy, live-birth, and implantation rates were 55%, 46%, and 43%, respectively. The odds of clinical pregnancy (odds ratio [OR] 3.08; 95% confidence interval [CI], 1.88-5.12) and live birth (OR 2.93; 95% CI, 1.79-4.85) were three times higher with day-5 blastocysts versus slower-growing day-6 vitrified blastocysts, irrespective of patient age at cryopreservation. Blastocysts from multinucleated embryos were half as likely to result in a live birth (OR 0.46; 95% CI, 0.22-0.91). A four -fold increase in live birth was observed if an expanded blastocyst was available for transfer. The inner cell mass-trophectoderm score correlated to positive outcomes in the univariate analysis. The implantation rate was statistically significantly higher for day-5 versus day-6 vitrified blastocysts (50% vs. 29%, respectively). CONCLUSION(S) The blastocyst expansion grade after warming was predictive of successful outcomes independent of the inner cell mass or trophectoderm score. Delayed blastulation and multinucleation were independently associated with lower live-birth rates in frozen cycles. Implantation potential of the frozen blastocysts available should be included in the decision-making process regarding embryo number for transfer.

The Use of Laparoscopy Simulation to Explore Gender Differences in Resident Surgical Confidence

Background. The objective of this study was to determine whether female surgical residents underestimate their surgical abilities relative to males on a standardized test of laparoscopic skill. Methods. Twenty-six male and female general surgery residents and 25 female obstetrics and gynecology residents at two academic centers were asked to predict their score prior to undergoing the Fundamentals of Laparoscopic Surgery standardized skills exam. Actual and predicted score as well as delta values (predicted score minus actual score) were compared between residents. Multivariate linear regression was used to determine variables associated with predicted score, actual score, and delta scores. Results. There was no difference in actual score based on residency or gender. Predicted scores, however, were significantly lower in female versus male general surgery residents (25.8 ± 13.3 versus 56.0 ± 16.0; p < 0.01) and in female obstetrics and gynecology residents versus male general surgery residents (mean difference 20.9, 95% CI 11.6–34.8; p < 0.01). Male residents more accurately predicted their scores while female residents significantly underestimated their scores. Conclusion. Gender differences in estimating surgical ability exist that do not reflect actual differences in performance. This finding needs to be considered when structuring mentorship in surgical training programs.

Ovarian transposition: a surgical option for fertility preservation.

OBJECTIVE To describe and demonstrate a novel surgical method for laparoscopic ovarian transposition. In this video, we present a unique minimally invasive technique for transposing the ovaries, whereby the ovary is tunneled through the peritoneum. DESIGN Video presentation of clinical article. The video uses animations and a surgical case to demonstrate the detailed surgical technique for laparoscopic ovarian transposition with a unique feature. Institutional review board approval was not required for this video presentation. Institutional review board approval is not required at the Cleveland Clinic for a case report of a single patient. SETTING Teaching University. PATIENT(S) A 29-year-old female patient diagnosed with rectal cancer. INTERVENTION(S) The patient underwent laparoscopic ovarian transposition followed by ovarian decortication for ovarian tissue freezing of the contralateral ovary, both performed in one laparoscopic surgery, before further chemotherapy and radiation. MAIN OUTCOME MEASURE(S) Value and feasibility of laparoscopic ovarian transposition using the unique feature of ovarian tunneling in maintaining the retroperitoneal location of the ovarian vessels and potentially preserving ovarian blood supply. RESULT(S) Creating a retroperitoneal tunnel for passing the ovary through is a feasible and effective technique, while performing laparoscopic ovarian transposition that can be performed in order to prevent the ovarian vessels from taking a sharp turn into the pelvic cavity and thereby preventing alteration of ovarian blood flow. CONCLUSION(S) Ovarian transposition is a great surgical option for fertility preservation in reproductive-aged women before they undergo gonadotoxic pelvic or craniospinal radiation. This surgical procedure is not a beneficial option for those patients receiving concomitant gonadotoxic chemotherapy. Ovarian transposition can be performed using different surgical techniques, including laparotomy and laparoscopy. Laparoscopic ovarian transposition is the preferred surgical technique described in the literature, because it is associated with more rapid recovery and less postoperative pain. This technique has been reported to have a success rate of 88.6% for preservation of ovarian function, as documented by measuring the gonadotropin levels after cancer treatment. Ovarian transposition is considered to be a safe and effective surgical option to prevent from premature ovarian failure and to optimize preservation of fertility.

Supraumbilical primary trocar insertion for laparoscopic access: the relationship between points of entry and retroperitoneal vital vasculature by imaging

OBJECTIVES Advances in laparoscopy have demonstrated that supraumbilical primary ports can be desirable in complex cases with large masses. This study evaluated distances to vital retroperitoneal vasculature that were encountered with 45- and 90-degree angle entry from the umbilicus and 2 commonly described supraumbilical entry points at 3 and 5 cm cephalad from the umbilicus. STUDY DESIGN Retrospective analysis of computed tomography scans of the abdomen and pelvis from 100 randomly selected women who were 18-50 years old with normal anatomy was performed. Three-dimensional models of sagittal sections were generated using IMPAX software. Measurements from the abdominal wall at the umbilicus and 3 and 5 cm cephalad with 45- and 90-degree angles to retroperitoneal structures were performed. RESULTS With 90-degree angle entry, the abdominal wall thickness (AWT) was thinnest at the umbilicus; however, the thickness at 3 and 5 cm was similar. AWT increased at all sites with 45-degree angle entry, and the same pattern was observed. AWT and intraperitoneal distance positively correlated with body mass index and supraumbilical entry points. With 90-degree angle entry, the aorta was 1.9 cm (95% confidence interval [CI], 1.4-2.4) and 2.5 cm (95% CI, 2.0-2.9) farther away at 3 and 5 cm cephalad compared with umbilical entry. In one-third of the cases, regardless of port placement, a vascular structure other than the aorta was the most anterior vessel. With 45-degree angle entry at the umbilicus, no vessels were encountered. With 45-degree angle entry at 3 and 5 cm cephalad, the aorta was the most anterior vessel in 1% and 2% of cases, respectively, and was noted to be 1.0 cm (95% CI, 1.0-1.0) and 2.3 cm (95% CI, 1.2-3.3) farther away than with 90-degree angle entry. A vessel other than the aorta was encountered in 4% and 7% of cases at 3 and 5 cm, respectively. CONCLUSION According to theoretic modeling, supraumbilical primary port placement can be implemented safely in laparoscopy. With supraumbilical entry, the distance to retroperitoneal vessels was greater than at the umbilicus. Compared with a 90-degree angle, with a 45-degree angle entry, it was uncommon to encounter vasculature, and all measured distances were greater.

Versatility of the suprapubic port in robotic assisted laparoscopic myomectomy

OBJECTIVE To demonstrate the multiple advantages of the suprapubic port in robotic assisted laparoscopic myomectomy. DESIGN Video demonstration of a robotic assisted laparoscopic myomectomy technique using a suprapubic incisional retractor (GelPOINT). SETTING Hospital. PATIENT(S) A 32-year-old primigravid women with heavy menstrual bleeding and pelvic pain with a 12-cm leiomyoma (International Federation of Gynecology and Obstetrics type 5). INTERVENTION(S) Illustrate a surgical approach during robotic assisted laparoscopic myomectomy with the use of a 5-cm suprapubic incision, an incisional retractor (GelPOINT) for the enucleation, and extraction of a large leiomyoma. MAIN OUTCOME MEASURE(S) The effective enucleation and extraction of a leiomyoma specimen using an incisional retractor and GelPOINT. The steps of the technique and the role of GelPOINT are demonstrated. RESULT(S) The procedure was performed without incident, and the patient experienced pain relief and lighter menses postoperatively. This technique has been performed successfully since June 2014 on 22 women. CONCLUSION(S) During a robotic assisted laparoscopic myomectomy the suprapubic incision is both advantageous and practical. The small incision allows the surgery to remain minimally invasive; the primary umbilical trocar is inserted under direct visualization in an already insufflated abdomen; the location of the incision allows the surgical assistant easy access to the port; the passing of the needles occurs under direct visualization with minimal camera manipulation; and last, the extraction of large tissue can be performed within a specimen pouch through this same suprapubic incision in a short period.

Myoma in Pregnancy

Uterine myomas (leiomyomas or fibroids) are common benign tumors, arising from the smooth muscle of the uterus. The true prevalence of fibroids is unknown as there is no screening program for asymptomatic women, but the estimated prevalence of myomas is 30 % in all women, 20–40 % in reproductive aged women and 40–60 % of women by age 35 [1]. The risk of myoma increases significantly with increasing age, and by age 50, 70–80 % of women will have had a fibroid [2]. Prevalence is two to three times higher in black women [3]. Decreased incidence is observed with increased parity. This effect is further amplified with childbearing from age 25 to 29 [1]. Factors that alter estrogen levels also modify risk. Smoking, exercise, and lean body mass decrease the incidence, while obesity and early menarche increases the risk. Despite strong associations with estrogen, there is no observed effect with oral contraceptives (Fig. 15.1) [1, 3]. Myomas are typically classified as one of three types: subserous, intramural or submucous, determined by location relative to the myometrium. Further descriptors include pedunculated, for those attached by a stalk, or cervical, based on location (Fig. 15.2).

Fertility and fertility preservation: knowledge, awareness and attitudes of female graduate students

Abstract Purpose: To evaluate the general knowledge of female graduate students on reproductive aging and fertility preservation options, as well as to investigate the perceptions, personal beliefs, and desires regarding fertility and preservation modalities. Materials and methods: A cross-sectional online survey study of female graduate students and medical trainees from academic institutions in Ohio was performed. Women were excluded if the online survey was incomplete or if they were >45 years. Results: Analysis of 590 surveys was performed (response rate of 26.3%). Ninety-four percent (557/590) of subjects were between 20 and 35 years. Our respondents tended to be nulliparous (87%), married or in a relationship (51%) and interested in future fertility (77%). The reasons cited for delaying childbearing were multi-factorial, with career building noted most commonly (69%). Nearly 60% of women reported they would consider fertility preservation in the future; however, the majority (87%) cited two or more barriers. When asked about their desire for information on fertility preservation, 28% desired to receive education on their choices and 36% wanted their Ob/Gyn to discuss fertility preservation options. Women >30 years were significantly more likely to desire future fertility, want more fertility preservation education and consider pursuing fertility preservation in the future. Conclusions: Graduate-level women often delay childbearing for professional pursuits. This study demonstrates a need for increased fertility preservation awareness and education, especially by Ob/Gyn providers.

Biomarkers for Endometriosis in Saliva, Urine, and Peritoneal Fluid

Endometriosis is a pain syndrome which affects 35–50% of women with chronic pelvic pain and/or infertility. It is frequently misdiagnosed leading to delays in patients obtaining appropriate treatments. The most accurate currently available mode of diagnosis is through laparoscopy with histological confirmation. In this chapter we describe noninvasive and semi-invasive modalities to obtain biologic biomarkers which may be an adequate screening tool for patients with endometriosis who are symptomatic with normal transvaginal ultrasounds, whom are at highest risk for diagnosis delay. In this chapter we will review noninvasive (urinary, salivary) and semi-invasive biomarkers (peritoneal), as screening and diagnostic methodologies for women symptomatic endometriosis and normal ultrasound findings. Few genetic markers have been identified through DNA amplification of buccal swabs as well as hormonal markers, and this is an area with lots of potential. Various urinary peptides and proteins are discussed, some with more potential than others, which require studies with larger sample sizes, and need to be studied in more diverse populations. We also review the extensively studied peritoneal biomarkers which include cytokines, immune modulators, and growth factors. Though many of the biomarkers described have a lot of potential, there is not one that stands above the rest. Validation of these studies in larger sample sizes including various study populations is required prior to their applicability into the clinical setting. It is most probable that the answer lies in the study of combination of biomarkers and the identification of ideal panel that can predict the diagnosis and the severity of endometriosis.