S.D. Spandorfer

Postoperative day 1 serum human chorionic gonadotropin level as a predictor of persistent ectopic pregnancy after conservative surgical management

OBJECTIVE To determine characteristics predictive of persistent ectopic pregnancy (EP). DESIGN Retrospective cohort study. SETTING Tertiary care, university hospital. PATIENT(S) All women treated surgically for an EP whose postoperative hCG levels were followed until complete resolution or determination of a persistent EP over a 54-month period. MAIN OUTCOME MEASURE(S) Final outcome defined as successful treatment or persistent EP. RESULT(S) Twenty-six (17.7%) of 147 patients were diagnosed with a persistent EP. An inverse relationship was noted between the percent decrease in hCG at postoperative day 1 and the incidence of persistent EP. A significantly greater percentage of persistent EPs were noted when the postoperative day 1 hCG fell < 50% from the initial preoperative hCG level (relative risk = 3.51 [1.25 to 6.68]). No case of persistent EP was noted if the postoperative day 1 hCG declined by > or = 77%. Surgical time differed significantly (129 minutes versus 101 minutes) between cases treated successfully as compared with cases in which conservative treatment failed. No other preoperative or intraoperative variables were found to be significantly different. CONCLUSION(S) Although no single postoperative hCG value is predictive of conservative surgical treatment for EP, a day-1 postoperative hCG value may be used as a predictor of persistent EP.

Granulocyte Macrophage-Colony Stimulating Factor Production by Autologous Endometrial Co-Culture Is Associated with Outcome for In Vitro Fertilization Patients with a History of Multiple Implantation Failures

PROBLEM: To determine whether granulocyte macrophage (GM)‐colony stimulating factor (CSF) produced by autologous endometrial co‐culture was associated with outcome in 53 patients with a history of multiple in vitro fertilization failures.

Autologous Endometrial Coculture in Patients with In Vitro‐Fertilization (IVF) Failure: Correlations of Outcome with Leukemia Inhibiting Factor (LIF) Production1

PROBLEM: To determine if LIF produced by autologous endometrial co‐culture (ECC) was associated with outcome in 46 patients with a history of multiple IVF failures.
 METHOD OF STUDY: The conditioned media (CM) from ECC cells exposed or non‐exposed to human embryos was analyzed for LIF.
 RESULTS: Exposure or non‐exposure to an embryo did not result in differing levels of LIF in the CM. LIF levels were significantly greater in the CM than in the serum controls (LIF was not found in the serum controls). Embryos grown on ECC demonstrated a significant improvement in number of blastomeres and fragmentation when compared to embryos grown in conventional media without ECC (6.7±1.3 vs. 5.6±1.2 blastomeres and 17.6%±9.3 vs. 26.4%±9.8 fragmentation; P<0.05). When LIF levels were detectable in the CM, the embryos grown in ECC were of improved quality as compared to the embryos grown only in conventional media and demonstrated a non‐significant increase in pregnancy rates (60 vs. 48%, P=0.50).
 CONCLUSIONS: We have demonstrated a significant improvement in embryo quality with ECC. The cells in the ECC express LIF. The presence of LIF in the CM was associated with embryonic development and clinical pregnancy.

Interleukin-1 levels in the supernatant of conditioned media of embryos grown in autologous endometrial coculture: correlation with outcome after in vitro fertilization.

PROBLEM: To determine if interleukin (IL)‐1 produced by autologous endometrial coculture (AECC) was associated with outcome in patients with a history of multiple in vitro fertilization (IVF) failures. METHOD OF STUDY: The conditioned media (CM) from AECC cells exposed or non‐exposed to human embryos was analyzed for IL‐1. RESULTS: Embryos grown on AECC demonstrated a significant improvement in number of blastomeres and fragmentation (frag) when compared to embryos grown in conventional media without ECC (6.4±1.3 vs. 5.5±1.2 blastomeres and 14.6±9.3% vs. 18.4±9.8% frag; P<0.008 and 0.003, respectively). When IL‐1α and IL‐1β were undetectable in the CM, the embryos grown in ECC were of improved quality as compared to the embryos grown only in conventional media. Conversely, IL‐1ra levels in the CM were positively associated with embryo quality. Exposure or non‐exposure to an embryo did not result in differing levels of IL‐1α, IL‐1β, or IL‐1ra in the CM. IL‐1β levels were negatively associated with clinical pregnancy outcome (3.3 pg/mL (pregnant, n=12) vs. 27.1pg/mL (not pregnant, n=17); P=0.008, Mann–Whitney U‐test). IL‐1α and IL‐1ra levels were not associated with outcome. CONCLUSIONS: We have demonstrated a significant improvement in blastomere number and frag with ECC. The presence of IL‐1β in the CM was negatively associated with embryonic development and clinical pregnancy. The presence of IL‐1α in the CM was negatively associated with embryonic development and the presence of IL‐1ra in the CM was positively associated with embryonic development. Whether IL‐1β itself interferes with successful outcome after embryo transfer or if it is a marker for undetected endometritis in the biopsy specimens remains to be determined.

Follicular flushing and in vitro fertilization outcomes in the poorest responders: a randomized controlled trial

STUDY QUESTION Does follicular flushing during oocyte retrieval improve the number of oocytes retrieved in the poorest responders? SUMMARY ANSWER Follicular flushing in the poorest responders does not increase the number of oocytes retrieved and may result in lower implantation and clinical pregnancy rates. WHAT IS KNOWN ALREADY Although previous studies have shown no beneficial effect of follicular flushing in normal responders, no study has demonstrated a detrimental effect and many IVF centers continue to perform this technique in poor responders. Data on follicular flushing in this patient group are limited, with no randomized trial to date assessing its utility in the poorest responders. STUDY DESIGN, SIZE, DURATION This randomized controlled trial compared the effects of follicular flushing and direct aspiration on IVF outcomes in the poorest responders, defined as having four or fewer follicles ≥12 mm on the day of hCG administration. Fifty patients were randomized during the 12-month enrollment period. PARTICIPANTS/MATERIALS, SETTING, METHODS The patients were treated at an academic fertility center at Weill Cornell Medical College, New York. MAIN RESULTS AND THE ROLE OF CHANCE Fifty women were randomized to follicular flushing (n = 25) or direct aspiration (n = 25). One patient in the direct aspiration group was canceled prior to oocyte retrieval for premature ovulation and was included in the intent-to-treat analysis. There was no difference in the number of oocytes retrieved with a median (IQR) of 4 (2-6) in the aspiration group versus 3 (2-5) in the flushing group (95% CI: -0.78, 1.98; P = 0.41). Patients who underwent follicular flushing had significantly fewer embryos transferred {1.7 [standard deviation (SD) 0.6] versus 2.5 (SD 1.2), P = 0.03}, a lower implantation rate (5.3 versus 34.2%, P = 0.006) and a lower clinical pregnancy rate (4 versus 36%, P = 0.01). The difference in pregnancy rates remained significant after adjusting for embryos transferred. LIMITATIONS, REASONS FOR CAUTION Findings, including results for secondary outcome measures, may not be generalizable to natural IVF cycles as these were excluded from the study. WIDER IMPLICATIONS OF THE FINDINGS This is the first randomized trial to evaluate the utility of follicular flushing in the poorest responders, and the first to demonstrate a potentially detrimental effect of flushing on IVF outcomes. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER NCT 01558141.

In vitro fertilization versus conversion to intrauterine insemination in the setting of three or fewer follicles: how should patients proceed when follicular response falls short of expectation?

OBJECTIVE To determine whether in vitro fertilization (IVF) cycles with suboptimal response should be converted to intrauterine insemination (IUI) or proceed to oocyte retrieval (OR). DESIGN Retrospective cohort. SETTING Academic medical center. PATIENT(S) All patients initiating IVF from January 2004 through December 2011. INTERVENTION(S) OR versus conversion to IUI. MAIN OUTCOME MEASURE(S) A total of 1,098 patients were identified whose IVF cycles were characterized by recruitment of three or fewer follicles, excluding patients with bilateral tubal disease or severe male factor. Cycles with three follicles were defined as those with three follicles ≥ 14 mm with no fourth follicle ≥ 10 mm. Cycles with two or fewer follicles were similarly defined. Outcomes were compared for patients proceeding with OR (n = 624) versus converting to IUI (n = 474). Age-adjusted relative risks for pregnancy were calculated, stratifying for number of follicles. RESULT(S) The likelihood of retrieving at least one mature oocyte (82.9% vs. 94.8% vs. 96.2%), having at least one zygote (61.9% vs. 76.8% vs. 84.2%), and undergoing transfer (57.1% vs. 73.0% vs. 83.3%) increased significantly with increasing follicle number. Patients with three or fewer follicles were 2.6 times more likely to achieve a live birth with IVF versus IUI (9.3% vs. 3.4%). This benefit was only apparent when at least two follicles were present. No benefit was gained by performing OR in the setting of one follicle. CONCLUSION(S) IVF compared with IUI presents superior pregnancy rates in the setting of two or more follicles. Assisted reproduction programs may benefit their patients by pursuing IVF in this scenario.

Histologic characteristics of the endometrium predicts success when utilizing autologous endometrial coculture in patients with IVF failure.

Purpose: To analyze the success of autologous endometrial coculture (AECC) in improving embryo quality and pregnancy outcome based on the histologic characteristic of the biopsy.Methods: Prospective study of 86 consecutive patients undergoing IVF utilizing AECC.Results: The patients were on average 37.4±4.0 years with a history of 2.6±1.8 failed previous attempts. An overall clinical pregnancy rate of 45.3% per ET was found. The embryos grown in AECC were of an improved quality in comparison to those grown in conventional media. 33.7% (29/86) of the biopsies were out of phase (>3 days). In-phase (IP) and OOP (out of phase) specimens both demonstrated an improvement in embryo quality. However, OOP endometrial biopsies that displayed significant retarded endometrial development (< cycle day 19) did not demonstrate an improvement in embryos grown on AECC as compared to IP endometrial biopsies or OOP endometrial biopsies that demonstrated at least an endometrial development of cycle day 19.Conclusions: We have demonstrated a significant improvement in embryo quality with AECC. We have also demonstrated that histologic dating of the endometrium is predictive of IVF outcome when utilizing AECC.

Surgical Management of Endometrial Polyps in Infertile Women: A Comprehensive Review

Endometrial polyps are benign localized lesions of the endometrium, which are commonly seen in women of reproductive age. Observational studies have suggested a detrimental effect of endometrial polyps on fertility. The natural course of endometrial polyps remains unclear. Expectant management of small and asymptomatic polyps is reasonable in many cases. However, surgical resection of endometrial polyps is recommended in infertile patients prior to treatment in order to increase natural conception or assisted reproductive pregnancy rates. There is mixed evidence regarding the resection of newly diagnosed endometrial polyps during ovarian stimulation to improve the outcomes of fresh in vitro fertilization cycles. Hysteroscopy polypectomy remains the gold standard for surgical treatment. Evidence regarding the cost and efficacy of different methods for hysteroscopic resection of endometrial polyps in the office and outpatient surgical settings has begun to emerge.

Impact of Newly Diagnosed Endometrial Polyps During Controlled Ovarian Hyperstimulation on In Vitro Fertilization Outcomes

STUDY OBJECTIVE To investigate the impact of newly diagnosed endometrial polyps during controlled ovarian hyperstimulation (COH) on the outcomes of fresh in vitro fertilization (IVF)-embryo transfer (ET) cycles. DESIGN A retrospective cohort study (Canadian Task Force classification II-3). SETTING An academic center. PATIENTS All patients initiating IVF cycles at the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine during a 1-year period. Patients were stratified into 2 groups based on the presence or absence of newly diagnosed endometrial polyps during COH. INTERVENTIONS IVF with fresh ET. MEASUREMENTS AND MAIN RESULTS Two thousand nine hundred ninety-three patients were identified: 60 in the polyp group and 2933 in the nonpolyp group. The overall positive pregnancy, clinical pregnancy, spontaneous miscarriage, and live birth rates were similar between the groups. The biochemical pregnancy rate was 18.3% in the polyp group compared with 9.6% in the nonpolyp group (p = .01). This represented a 2-fold increased odds of biochemical pregnancy in the polyp group (odds ratio = 2.12; 95% confidence interval, 1.09-4.12) compared with the nonpolyp group. CONCLUSION Newly diagnosed endometrial polyps during COH is associated with an increased biochemical pregnancy rate but ultimately does not adversely impact clinical pregnancy or live birth rates after fresh IVF-ET.

Effect of Methotrexate or Salpingectomy for Ectopic Pregnancy on Subsequent In Vitro Fertilization-Embryo Transfer Outcomes.

OBJECTIVE To investigate the effect of methotrexate (MTX) or salpingectomy for ectopic pregnancy on the outcomes of subsequent in vitro fertilization (IVF)-embryo transfer (ET) cycles. DESIGN Retrospective cohort study (Canadian Task Force Classification II-3). SETTING Academic center. PATIENTS All patients undergoing fresh IVF-ET between January 2004 and July 2013 after treatment of an ectopic pregnancy with MTX or salpingectomy in the preceding IVF-ET cycle were analyzed for potential inclusion. INTERVENTION MTX or laparoscopic salpingectomy for an ectopic pregnancy followed by a subsequent IVF-ET cycle. MEASUREMENTS AND MAIN RESULTS A total of 144 patients with sonographically confirmed ectopic pregnancies were identified during the study period. Of these, 107 (74.3%) patients were treated with MTX and 37 (25.7%) were treated with laparoscopic salpingectomy. Eighty-eight patients (82.2%) in the MTX group and 22 patients (59.4%) patients in the salpingectomy group underwent a subsequent IVF-ET cycle. There were no significant differences in demographic data or baseline cycle characteristics between the 2 groups. No difference was observed in basal follicle-stimulating hormone (FSH) level before and after MTX or salpingectomy treatment. Indicators of ovarian responsiveness, including total days of stimulation, total dosage of gonadotropins, and number of mature oocytes before and after either treatment, were comparable in the 2 groups. The number of doses of MTX (1 vs > 1) did not correlate with changes in ovarian response. The pregnancy outcomes, specifically live birth, were equivalent in the 2 groups. Comparing post-MTX cycles and post-salpingectomy cycles, patients in the latter group required higher doses of gonadotropins (+705 IU vs +221.5 IU; p < .01), although the number of mature oocytes remained similar in the 2 groups. CONCLUSION Treatment of ectopic pregnancies with MTX or salpingectomy might not adversely affect ovarian reserve, ovarian responsiveness, or subsequent IVF cycle outcomes. However, in our study cohort, patients treated with MTX, those s treated with laparoscopic salpingectomy required higher gonadotropin doses in a subsequent cycle to attain the same number of mature oocytes.