Christopher B. Morse

Impact of endometriosis on in vitro fertilization outcomes: an evaluation of the Society for Assisted Reproductive Technologies Database

OBJECTIVEnTo assess the impact of endometriosis, alone or in combination with other infertility diagnoses, on IVF outcomes.nnnDESIGNnPopulation-based retrospective cohort study of cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database.nnnSETTINGnNot applicable.nnnPATIENT(S)nA total of 347,185 autologous fresh and frozen assisted reproductive technology cycles from the period 2008-2010.nnnINTERVENTION(S)nNone.nnnMAIN OUTCOME MEASURE(S)nOocyte yield, implantation rate, live birth rate.nnnRESULT(S)nAlthough cycles of patients with endometriosis constituted 11% of the study sample, the majority (64%) reported a concomitant diagnosis, with male factor (42%), tubal factor (29%), and diminished ovarian reserve (22%) being the most common. Endometriosis, when isolated or with concomitant diagnoses, was associated with lower oocyte yield compared with those with unexplained infertility, tubal factor, and all other infertility diagnoses combined. Women with isolated endometriosis had similar or higher live birth rates compared with those in other diagnostic groups. However, women with endometriosis with concomitant diagnoses had lower implantation rates and live birth rates compared with unexplained infertility, tubal factor, and all other diagnostic groups.nnnCONCLUSION(S)nEndometriosis is associated with lower oocyte yield, lower implantation rates, and lower pregnancy rates after IVF. However, the association of endometriosis and IVF outcomes is confounded by other infertility diagnoses. Endometriosis, when associated with other alterations in the reproductive tract, has the lowest chance of live birth. In contrast, for the minority of women who have endometriosis in isolation, the live birth rate is similar or slightly higher compared with other infertility diagnoses.

Management of Large Ovarian Neoplasms in Pediatric and Adolescent Females

The overwhelming majority of ovarian cysts in pediatric and adolescent girls are physiologic; however, large simple and complex ovarian lesions often require surgical intervention due to the increased risk of neoplasia. In this review article, we discuss the preoperative evaluation and intraoperative management of large ovarian neoplasms. We review the current literature regarding long term ovarian function and fertility, rates of recurrence and residual disease, and novel surgical approaches. Managing large ovarian neoplasms in the pediatric and adolescent population requires careful preoperative and intraoperative care to optimally resect neoplasia while maximizing fertility and minimizing pain.

Route of hysterectomy and surgical outcomes from a statewide gynecologic oncology population: is there a role for vaginal hysterectomy?

BACKGROUNDnRecent policy changes by insurance companies have been instituted to encourage vaginal hysterectomy (VH) as the preferred route for removal of the uterus. It is not known if advantages of VH for benign indications apply to women with gynecologic cancer.nnnOBJECTIVEnThe goal of this study was to assess trends in surgical approach to hysterectomy among gynecologic cancer patients and to evaluate outcomes by approach. We hypothesized that, among gynecologic oncology patients, postoperative complications and hospital stay would differ by surgical approach, and that advantages of VH for benign indications may not apply to gynecologic cancer patients.nnnSTUDY DESIGNnWe performed a population-based retrospective cohort study of cervical, endometrial, or ovarian/fallopian tube cancer patients treated surgically in Washington State from 2004 through 2013 using the Comprehensive Hospital Abstract Reporting System. Surgery was categorized as abdominal hysterectomy (AH), laparoscopic hysterectomy (LH), or VH. We determined rate of surgical approach by year and the association with length of stay, 30-day readmission rate, and perioperative complications.nnnRESULTSnWe identified 10,117 patients who underwent surgery for gynecologic cancer, with 346 (3.4%) VH, 2698 (26.7%) LH, and 7073 (69.9%) AH. Patients undergoing AH had more comorbidities than patients with VH or LH (Charlson Comorbidity Index ≥2: 11.3%, 7.9%, and 8.1%, respectively; P < .001). From 2004 through 2013 AH and VH declined (94.4-47.9% and 4.4-0.8%, respectively; P < .001) while LH increased from 1.2-51.4% in 2013 (P < .001). Mean length of stay was 4.6 days for women undergoing AH and was 1.9 days shorter for VH (95% confidence interval, 1.6-2.3 days) and 2.6 days shorter for LH (95% confidence interval, 2.4-2.7 days) (P < .001). Risk of 30-day readmission for patients undergoing LH was 40% less likely compared to AH but not different for VH vs AH.nnnCONCLUSIONnAH and LH remain the preferred routes for hysterectomy in gynecologic oncology. Over the past decade, there has been a significant shift to LH with lower 30-day readmission and complication rates. There may be a limited role for VH in select patients. Current efforts to standardize the surgical approach to hysterectomy should not apply to patients with known or suspected gynecologic cancer.

Association of the very early rise of human chorionic gonadotropin with adverse outcomes in singleton pregnancies after in vitro fertilization

OBJECTIVEnTo determine if very early serum hCG, a marker of trophoblast differentiation, is associated with adverse perinatal outcomes in singleton pregnancies.nnnDESIGNnRetrospective cohort study.nnnSETTINGnUniversity fertility program.nnnPATIENT(S)nA total of 360 singleton IVF live births.nnnINTERVENTION(S)nSerial hCG measurements were used to determine the within-woman slope for hCG (hCG rise).nnnMAIN OUTCOMES MEASURE(S)nPrimary outcomes included birth weight and gestational age at delivery. Statistical comparisons used t test, chi-square test, and linear and logistic regressions as appropriate.nnnRESULT(S)nhCG rise was positively associated with birth weight but not gestational age at delivery. Infant sex, gestational age, and type of embryo transfer (fresh vs. frozen/thawed) were significantly associated with birth weight and confounded the associations of interest. hCG rise was slower among subjects delivering an infant with low birth weight (slope 0.386 ± 0.05 vs. 0.407 ± 0.06) or small for gestational age (slope 0.371 ± 0.07 vs. 0.406 ± 0.06). Analysis of hCG rise by quartile showed that, compared with the first quartile (slowest), subjects with a rate of hCG rise in the fourth quartile (fastest) had a significantly decreased risk of delivering an infant of low birth weight. No relationship was noted between hCG rise and hypertensive disorders of pregnancy.nnnCONCLUSION(S)nSlower very early first-trimester hCG rise is associated with low birth weight but not gestational age at delivery among singleton IVF conceptions. The rate of increase in serum hCG may reflect early trophoblast differentiation and placentation and, possibly, may predict subsequent development.

Elevated tumor mutational burden and prolonged clinical response to anti-PD-L1 antibody in platinum-resistant recurrent ovarian cancer

Highlights • We report an ovarian cancer patient with a prolonged response to immunotherapy.• Comprehensive genomic profiling may detect patients who benefit from immunotherapy.• Mutational burden thresholds for ovarian cancer may be lower than other cancers.

Premalignant alterations in breast and endometrium associated with a PTEN mutation in a woman with Cowden syndrome: implications for preventive care☆

Highlights • This case report documents the in vivo process of malignant transformation in a patient with Cowden syndrome.• PTEN-driven oncogenesis may proceed through a stage of pre-invasive intra-epithelial neoplasm.• Our findings have important implications for preventive care and for pathologic sampling at the time of prophylactic surgery.

Neoplastic cellularity is associated with clinical and molecular features of high-grade serous ovarian carcinoma

OBJECTIVEnMost molecular analyses of high-grade serous ovarian, peritoneal and fallopian tube carcinomas (HGSC) require ≥70% tumor (neoplastic) cell nuclei. We characterized the distribution of the percentage of neoplastic nuclei (PNN) in a large cohort of HGSC and correlated PNN with clinical outcomes to determine the fraction of cases outside this range and whether this cut-off introduces selection bias.nnnMETHODSnSubjects were prospectively enrolled and normal and neoplastic tissues were snap-frozen. All subjects had grade 2 to 3 HGSC. Subjects that received neoadjuvant chemotherapy were excluded. PNN was determined by estimating the fraction of neoplastic nuclei relative to non-neoplastic nuclei on a representative hematoxylin and eosin stained frozen section from the primary neoplasm. Germline BRCA mutation status was determined with Sanger or BROCA sequencing.nnnRESULTSnPNN was <70% in 101 (33%) of 306 cases. PNN was significantly higher among subjects without optimal cytoreduction (P=0.018). 55 subjects had germline BRCA1/BRCA2 mutations. HGSC associated with BRCA2 but not BRCA1 mutations had significantly lower PNN compared to HGSC in non-carriers (54% vs. 70%, P=0.018). Overall survival was not significantly different between subjects with <70% or ≥70% PNN (median survival 51.8 vs. 46.6months, P=0.858).nnnCONCLUSIONSnOne-third of HGSC has PNN <70%. Higher PNN is associated with suboptimal cytoreduction, while lower PNN is associated with inherited BRCA2 mutations. Our findings suggest a nonrandom distribution of PNN that may reflect cancer biology. Further studies exploring the stromal microenvironment are needed. Molecular analyses of HGSC selected for high PNN exclude a significant fraction of patients.