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Background: Severe forms of genital endometriosis are known to be associated with infertility and its subsequent treatment failure. Both gonadotropin-releasing hormone analogs (a-GnRH) and dienogest have been suggested as additional hormone therapy for patients with endometriomas. However, the result of hormonal suppression before an in vitro fertilization (IVF) cycle remains undetermined. Materials and methods: A prospective cohort study of 144 infertile women planning IVF after laparoscopic surgery of ovarian endometriomas was conducted at our department in 2012-2015. Patients were divided into three groups: group I (N ¼ 38) with dienogest course, group II (N ¼ 70) with a-GnRH group III (N ¼ 70) without any hormonal therapy within 6 months preceding IVF. Results: The study groups did not differ by removed endometriomas size and ovarian reserve indicators. The gonadotropin dose per Cycle was higher, while the number of retrieved oocytes was lower in group III patients (p < .001). In women with dienogest pretreatment, clinical pregnancy rate was 2.5 times (44.7% versus 16.7%, p ¼ .012) and delivery rate -three times higher (36.8% versus 11.1%, p ¼ .013) as compared with those from group III. Conclusions: The present study confirms the necessity of pre-cycle medical interventions in women with ovarian forms of endometriosis undergoing IVF. We suggest dienogest to be possibly more efficient treatment option for this kind of patients.

Background: Ectopic pregnancy (EP) has been reported to occur in 1.4-5.4% of all clinical pregnancies resulting from in vitro fertilization (IVF) and embryo transfer (ET). Data on factors associated with abnormal embryo implantation following assisted conception are limited. Materials and methods: A systematic review and meta-analysis was performed to determine whether there is an association between the day (cleavage-stage, D3, versus blastocyst, D5) or the type (fresh versus frozen/thawed) of ET and EP rate. Risk factors for EP were evaluated in a retrospective study of 1194 women, who achieved pregnancy at our IVF unit between 2010 and 2016. Results: Sixteen papers were considered for the meta-analysis. EP rate did not differ between D3 and D5 fresh ET groups (RR ¼ 0.99, 95%CI: 0.76-1.30) and was higher after fresh versus frozen ET (RR ¼ 1.56, 95%CI: 1.25-1.95). At our clinic, 21 (1.76%) pregnancies were documented as ectopic. The risk of EP was associated with tubal pathology (OR ¼ 3.37, 95%CI: 1.39-8.2), previous appendectomy and past chlamydial infection. Conclusions: Present meta-analysis suggests that EP rate is similar following fresh blastocyst and cleavage ETs, but is significantly reduced after frozen compared with fresh ET. Our own findings demonstrate that tubal pathology has the major impact on EP occurrence following assisted conception.

Background: We previously showed that intense dose-dense (idd) epirubicin (E), paclitaxel (T), cyclophosphamide (C) results in a superior DFS and OS compared to conventionally dosed EC-T in pts with primary breast cancer (PBC) and ≥4 involved lymph nodes (LN) (Möbus et al JCO 2010). In the GAIN study, the intense dose-dense strategy has been further investigated as well as the adjuvant application of ibandronate (I). We here report on the planned interim efficacy analysis after 50% (N&gt;401) of the required events have occurred. Methods: A prospective, multi-center, controlled, non-blinded, randomized phase III trial investigating ETC (E: 150 mg/m2, T:225 mg/m2, C:2500–2000 mg/m2, i.v. day 1, q15 for 3 cycles each: A1); or EC→TX (E: 112.5 mg/m2 + C: 600 mg/m2, i.v. day 1, q 15 for 4 cycles→T: 67.5 mg/m2 i.v. day 1, q 8 for 10 weeks + X: 2000 mg/m2 p. o. day 1–14, q 22 for 4 cycles: A2). Pts were further randomized in a 2:1 ratio to receive ibandronate: 50 mg/day p.o. for 2 years (B1) or observation (B2). Pts received a primary prophylaxis with either epoetin β or darbepoetin α and pegfilgrastim during ETC or EC. After recruitment of 1500 pts prophylactic ciprofloxacin was implemented and the dose of C was reduced to 2000 mg/m2. Eligibility: Females ≥18 and &lt;65 years, histologically confirmed LN positive uni- or bilateral PBC; adequate surgery, ≥1 pos.LN; ECOG ≤2; written informed consent. Primary objective:compare DFS A1 vs. A2 and B1 vs.B2. Secondary objectives: OS, safety, incidence of secondary primaries, and EFS in subgroups of hormone sensitivity and number of pos. LN between arms; assessment of compliance; determine prognostic factors. 3000 pts with 801 events were needed to show an increase of 5-year DFS from 75% to 79% for pts receiving EC→TX and 728 events to show an increase of 5-year DFS from 75% to 79.5% for pts receiving I, assuming a drop-out rate of 5%, α=0.05 (two-sided)and 1-β =80%. An interim analysis for both primary objectives was planned after 50% of the expected events occurred. Safety results have been reported previously (Möbus et al. SABCS 2009). Results: 3023 patients were randomized between 06/2004 and 08/2008.1512 received ETC and 1511 EC→TX. 29pts never started therapy, 14 in ETC, 15 in EC→TX. Median follow-up is 38.7 months. Median age was 50 years; pN1 (37.7%), pN2 (35.4%); pN3 (26.9%); 77.4% had ductal invasive carcinoma, 46.6% were grade 3; 76.7% had hormone receptor-positive tumors, 22% were HER2−positive. 405 events have occurred by 12.05.2011.380pts relapsed and 25pts. died w/o relapse. The interim futility boundary for chemotherapy was not crossed. For the ibandronate question the futility boundary was reached. There was no difference in DFS and OS between the patients with and without ibandronate (DFS log-rank p=0.593; HR 1.059; 95%CI 0.861−1.301; OS log-rank p=0.801 HR 0.961; 95% CI 0.705−1.31). Conclusion: The GAIN study demonstrated that adjuvant ibandronate does neither improve DFS nor OS in primary node positive breast cancer after treatment with dose-intensified chemotherapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S2-4.

To estimate the efficacy of growth hormone (GH) co-treatment within an antagonist protocol in IVF/ICSI cycles in poor responders. A prospective observational study involving 50 patients underwent a standard antagonist protocol with or without GH co-treatment. GH was administered by a daily subcutaneous injection of 1,33 mg (equivalent to 4 IU) starting from day 1 of ovarian stimulation until the day of 10,000 human chorionic gonadotropin (hCG) triggering . Concentrations of GH, insulin-like growth factor I (IGF-I) and IGF binding protein-3 (IGFBP-3) in serum and follicular fluid were the subject matter of analysis. The GH co-treatment significantly lowered the effective dose of gonadotropins, duration of stimulation, IGFBP-3 level in serum and follicular fluid on the day of oocyte retrieval. The total number of oocytes as well as the number of metaphase II stage (MII) oocytes, two pronucleus (2 pn) zygotes, good-quality transferred embryos was significantly higher in the GH þ group. Pregnancy was achieved in patients GH þ group only. Positive correlation was found between IGF-I level in follicular fluid, dynamics of IGFBP-3 level changes during stimulation protocol and the number of good-quality transferred embryos in the GH þ group. GH administration in IVF/ICSI cycles for poor responders raises ovarian sensitivity to the gonadotropin exogenous influence, increasing number of high-quality embryos and the probability of pregnancy. ARTICLE HISTORY