Spontaneous triggering of ovulation versus HCG administration in patients undergoing IUI: a prospective randomized study.

The objective of this prospective randomized study was to assess whether spontaneous triggering of ovulation by detecting LH rise with serial serum testing, results in higher pregnancy rates as compared with administration of human chorionic gonadotrophin (HCG) in patients undergoing intrauterine insemination (IUI) in natural cycles. The trial was registered in clinicaltrials.gov as NCT01414673. Three hundred patients treated by IUI in natural cycles at the Centre of Reproductive Medicine of the Dutch-Speaking Brussels Free University were randomized to either spontaneous triggering of ovulation (spontaneous LH group) (n=150) or administration of HCG (n=150). Donor spermatozoa was used in 197/300 patients (65.67%). The duration of the follicular phase was significantly higher in the spontaneous LH group as compared with the HCG group (P=0.004). However, the ongoing pregnancy rate was significantly higher in the spontaneous LH group as compared with the HCG group (34/150 versus 16/150, P=0.008; difference 12.0%, 95% CI - 3.6 to 20.4). The use of LH for timing ovulation in natural cycles might be the best way to maximize the probability of pregnancy for patients undergoing IUI. It remains unclear whether the probability of pregnancy is associated with the mode of ovulation triggering in intrauterine insemination (IUI) natural cycles. The aim of this study was to assess prospectively whether spontaneous triggering of ovulation by detecting LH rise results in higher pregnancy rates as compared to administration of human chorionic gonadotrophin (HCG) in patients undergoing IUI. Based on our results, spontaneous triggering of ovulation is associated with significantly higher ongoing pregnancy rates compared with administration of HCG in patients undergoing IUI. Therefore, the use of LH for timing ovulation in natural cycles might be the best way to maximize the probability of pregnancy for patients undergoing IUI.

Bladder perivascular epithelioid cell tumor: a novel rare neoplasm.

Perivascular epithelioid cell tumors (PEComas) have recently been defined as a group of neoplasms that have in common the co-expression of melanocytic and smooth muscle markers. We report a novel case of a rare bladder PEComa and we review the relevant literature.

Is earlier administration of human chorionic gonadotropin (hCG) associated with the probability of pregnancy in cycles stimulated with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone (GnRH) antagonists? A prospective randomized trial.

OBJECTIVE: To evaluate the association of timing of hCG administration and probability of pregnancy in patients stimulated with recombinant FSH/GnRH antagonists for IVF. DESIGN: Prospective randomized controlled clinical trial. SETTING: Dutch-speaking Free University of Brussels. PATIENT(S): One hundred twenty patients, aged <40 years, treated by IVF or intracytoplasmic sperm injection. INTERVENTION(S): Ovarian stimulation was achieved using recombinant FSH starting on day 2 of the menstrual cycle at a fixed dose. To inhibit premature LH surge, daily GnRH antagonist was used from day 6 of stimulation. Triggering of final oocyte maturation was performed using 10,000 IU of hCG. Patients were randomized to receive hCG either as soon as three or more follicles of size ≥16 mm were present on ultrasonography (early-hCG group) or 1 day after the above criterion was met (late-hCG group). MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate. RESULT(S): Significant differences were observed between the early-hCG and the late-hCG group regarding E(2) (1,388 ± 931 [mean ± SD] vs. 2,040 ± 1,231 pg/mL, respectively) and P (0.8 ± 0.3 vs. 1.1 ± 0.5 ng/mL, respectively) levels on the day of hCG administration and the number of metaphase II oocytes (9.2 ± 7.1 vs. 6.1 ± 4.9, respectively). No significant differences were observed between the early-hCG and the late-hCG group regarding positive hCG (46.2% vs. 50%, respectively) and ongoing pregnancy rates (34.6% vs. 40.7%, respectively). CONCLUSION(S): The current study provides evidence that earlier administration of hCG is not associated with the probability of pregnancy in cycles stimulated with recombinant FSH and GnRH antagonists.

High exposure to progesterone between the end of menstruation and the day of triggering final oocyte maturation is associated with a decreased probability of pregnancy in patients treated by in vitro fertilization and intracytoplasmic sperm injection.

OBJECTIVE: To investigate the association between the probability of pregnancy and hormone exposure between the end of menstruation and the day of triggering final oocyte maturation (menstruation-free interval). DESIGN: Prospective study. SETTING: University. PATIENT(S): One hundred women (aged ≤ 39 years) stimulated with a fixed dose of recombinant follicle-stimulating hormone (200 IU). INTERVENTION(S): Daily gonadotropin-releasing hormone antagonist (GnRH, 0.25 mg) used from day 6 of stimulation onward, final oocyte maturation triggered by administration of 10,000 IU of human chorionic gonadotropin (hCG) as soon as ≥ 3 follicles ≥ 17 mm were present, and hormone assessment performed at initiation of stimulation, on the first day after menstruation had stopped, on the day of antagonist initiation, and on the day of hCG administration. MAIN OUTCOME MEASURE(S): The association between hormone exposure during the menstruation-free interval and the probability of ongoing pregnancy. RESULT(S): The exposure to progesterone during the menstruation-free interval was statistically significantly higher in patients who did not become pregnant compared with those who did (4.20 ± 2.54 vs. 3.13 ± 1.14, respectively). Binary logistic regression confirmed the adverse effect of the increased exposure to progesterone for the achievement of pregnancy. CONCLUSION(S): In recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in vitro fertilization/intracytoplasmic sperm injection cycles, a lower probability of pregnancy is associated with a higher exposure to progesterone during the menstruation-free interval.

Aromatase inhibitors in post-menopausal endometriosis.

Postmenopausal endometriosis is a rare clinical condition. The diagnosis and treatment of an endometriotic lesion in postmenopausal women is complicated. First line treatment choice should be surgical, given that there is a potential risk of malignancy. Medical treatment may be considered as second line or as an alternate first line treatment whenever surgery is contradicted and aims to alter the hormonal pathway leading to endometriosis progress. Different hormonal regimens have been administered to these patients, with conflicting however results. Aromatase inhibitors (AIs) represent one of the most recently used drugs for postmenopausal endometriosis. Clinical data for the use of (AIs) in postmenopausal patients is scarce. Up to date only 5 case reports are available regarding the use of these agents in postmenopausal women. Although definite conclusions may be premature, AIs appear to considerably improve patients' symptoms and reduce endometriotic lesions size. Nonetheless the subsequent induced reduction in estrogen production, leads to certain short-term and long-term adverse effects. Despite the limited available data, AIs appear to represent a new promising method which may improve symptoms and treat these patients, either as first line treatment, when surgery is contraindicated or as a second line for recurrences following surgical treatment. However, careful monitoring of patients' risk profile and further research regarding long-term effects and side-effects of these agents is essential prior implementing them in everyday clinical practice.

No relationship between the type of pituitary suppression for IVF and chromosomal abnormality rates of blastomeres: an observational study.

OBJECTIVE: To investigate whether the incidence of chromosomally abnormal blastomeres is related to the type of pituitary suppression used in ovarian stimulation. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENT(S): The study involved 694 consecutive cycles; 320 belonged to agonist group and 374 to antagonist group, of patients' ≤ 37 years of age who underwent preimplantation genetic screening between October 1, 1992 until December 31, 2006. All of them (and their partners) had normal karyotyping results. Only the data of patients who had at least one embryo biopsy were analyzed. INTERVENTION(S): Preimplantation genetic screening (PGS). MAIN OUTCOME MEASURE(S): The primary outcome measure was detection of abnormal blastomeres on the total number of embryos analyzed. RESULT(S): The total abnormal ratio was statistically similar between the embryos of the two study groups (49.9 ± 28.1 vs. 50.2 ± 26.6). Likewise, a multivariate (linear regression) analysis indicated that the total abnormality ratio was not influenced by the type of stimulation when simultaneously adjusting for age, rank of trials, indication for preimplantation genetic screening, total gonadotropin amount, number of cumulus-oocyte complexes, and number of two pronuclear oocytes embryos. No difference was observed in ongoing pregnancy rates between agonists and antagonists (26.6% vs. 23.3%, respectively). CONCLUSION(S): Based on our findings there is no difference in the proportion of abnormal blastomeres either when using gonadotropin-releasing hormone (GnRH) agonist, or antagonist protocol.

Ex-vivo oocyte retrieval for fertility preservation.

OBJECTIVE: To report a novel fertility preservation strategy in a woman with recurrent serous borderline ovarian tumor in the conserved ovary involving ex-vivo retrieval of in vivo matured oocytes and subsequent embryo cryopreservation. DESIGN: Case report. SETTING: Tertiary infertility care unit. PATIENT(S): A 27-year-old woman presented for follow-up visit with a history of borderline serous adenocarcinoma treated conservatively with left oophorectomy and fertility-sparing laparoscopic staging. Ultrasound scan revealed a recurrent disease in the right ovary. INTERVENTION(S): Ex-vivo retrieval of mature oocytes after ovarian stimulation. MAIN OUTCOME MEASURE(S): Fertility preservation. RESULT(S): The patient underwent ovarian stimulation followed by a laparotomy and oophorectomy on the day of oocyte retrieval. A puncture of the follicles was performed in the operating theatre with a maximum ischemia time of 14 minutes. Eleven mature oocytes were aspirating, resulting in seven zygotes for cryopreservation. CONCLUSION(S): Mature oocytes can be successfully retrieved ex-vivo from the oophorectomy specimen after a controlled ovarian hyperstimulation (COH) protocol. This method provides a possible strategy for fertility preservation in patients with recurrent ovarian cancer without the risk of cancer cells spillage associated with the standard transvaginal oocyte retrieval.

Transfer of cryopreserved - thawed embryos in hCG induced natural or clomiphene citrate cycles yields similar live birth rates in normo-ovulatory women.

INTRODUCTION: the purpose of this retrospective analysis is to compare the efficiency of hCG-induced natural and Clomiphene citrate (CC) cycles in normovulatory patients undergoing frozen embryo transfer (FET). MATERIALS AND METHODS: it was retrospectively conducted in the Dutchspeaking Free University of Brussels and covered the period from April 2003 to August 2006. In particular, 428 day-three FET cycles belonging to the two comparative groups were recruited. Of these FET cycles, 261 were hCG-induced natural and 167 clomiphene citrate-induced cycles. RESULTS: no statistically significant difference was observed in live birth rate between CC and natural group (22.2% versus 22.6%), respectively (P = 0.708). Except for the number of embryos transferred (1.72 ± 0.46 for cc group versus 1.63 ± 0.48 for natural group, p = 0.045), no other parameters seem to influence the outcome. discussion: To our knowledge, this is the first attempt to investigate which of the above mentioned regimens is optimal for normo-ovulatory women in FET cycles. A similar delivery outcome was observed for hCG-induced natural and CC-induced cycles used for endometrial preparation in FET.

Higher birth rate after recombinant hCG triggering compared with urinary-derived hCG in single-blastocyst IVF antagonist cycles: a randomized controlled trial.

In a prospective randomized controlled trial, 119 patients were randomized to receive either recombinant hCG (250 µg) or urinary-derived hCG (10,000 IU) for final oocyte maturation in an antagonist protocol with a fixed dose of recombinant FSH (187.5 IU) and predefined single blastocyst transfer. The delivery rate was improved in the recombinant hCG group compared with the urinary-derived hCG group (44.1 vs. 25.7, respectively); however, adequately powered randomized controlled trials are justified to ascertain whether this difference is true.

Vaginal progesterone supplementation has no effect on ongoing pregnancy rate in hCG-induced natural frozen-thawed embryo transfer cycles.

OBJECTIVE: The purpose of this study is to assess the effect of luteal phase supplementation (LPS) on pregnancy rates in human chorionic gonadotropin (hCG)-induced natural frozen-thawed (FET) cycles. STUDY DESIGN: All performed hCG-induced natural FET cycles from January 2006 until August 2007 were retrospectively identified. The study group consisted of 452 cycles: 243 supplemented with progesterone administration (600 mg natural micronized progesterone in three separate doses) and 209 without progesterone. Analysis was limited to cycles where embryos were cryopreserved on day 3. Final oocyte maturation was achieved by hCG when endometrial thickness of >or=7 mm and a follicle of 17 mm were present on ultrasound. RESULTS: No statistically significant differences were observed in ongoing pregnancy rate between the two groups (22% versus 21%, p=0.8; difference +1%; 95% confidence interval (CI): -6.5 to +8.7). The non-significant effect of the presence or not of luteal support on pregnancy rate was confirmed by logistic regression (odds ratio (OR): 0.9, 95% CI: 0.54-1.47, P=0.64). A previous pregnancy following fresh embryo transfer (OR: 6.04, 95% CI: 3.63-10.02, P=0.001) and increased endometrial thickness (OR: 1.25, 95% CI: 1.11-1.41, P=0.001) significantly affected the achievement of ongoing pregnancy, whereas the association between embryo score and achievement of pregnancy was marginally significant (OR:0.28, 95% CI: 0.08-0.97, P=0.05). CONCLUSION: There is no convincing evidence to support the use of LPS in hCG-induced natural FET cycles, since there is no luteal phase defect. Further prospective randomized studies are necessary to confirm these findings.

Cryopreserved-thawed human embryo transfer: spontaneous natural cycle is superior to human chorionic gonadotropin-induced natural cycle.

OBJECTIVE: To assess whether there is a difference in the ongoing pregnancy rate after transferring frozen-thawed embryos in natural cycles with spontaneous LH-P rise compared with natural cycles controlled by hCG for final oocyte maturation and ovulation. DESIGN: Randomized controlled trial. SETTING: Tertiary referral center. PATIENT(S): A total of 168 patients were assigned randomly to undergo frozen ET on day 3 from October 2007 until November 2008. Finally, analysis was performed in 124 patients; 61 belonged to the spontaneous LH group and 63 to the hCG group. INTERVENTION(S): In the spontaneous LH group the transfer was planned 5 days after the LH surge. In the hCG group, the cryopreserve ET was planned 5 days after the administration of 5000 IU of hCG, when an endometrial thickness of ≥7 mm and a follicle of ≥17 mm were present on ultrasound examination. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate. RESULT(S): The study was terminated early, when a prespecified interim analysis found a significantly higher ongoing pregnancy rate in the spontaneous LH group as compared with the hCG group (31.1% vs. 14.3%; difference 16.9%, 95% confidence interval 4.4%-28.8%). CONCLUSION(S): The results suggest the superiority of the natural cycle as compared with the natural cycle controlled by hCG administration in cryothawed ET cycles.

Is the use of donor sperm associated with a higher incidence of preeclampsia in women who achieve pregnancy after intrauterine insemination?

OBJECTIVE: To evaluate the incidence of preeclampsia after intrauterine insemination (IUI) with either donor's or partner's sperm in women with primary infertility. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Between January 1999 and December 2006, 823 women who achieved pregnancy after IUI and delivered at > or =24 weeks of gestation were reviewed. Only women with primary infertility and no known medical disorders were included. On the basis of the available outcome data, the final analysis was performed in 713 pregnancies (438 pregnancies using donor's sperm and 275 pregnancies using partner's sperm). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The incidence of preeclampsia. RESULT(S): The incidence of preeclampsia in pregnancies resulting from donor sperm was higher than in the partner insemination group: 10.9% (48/438) versus 7.2% (20/275), respectively (difference, 3.7; 95% confidence interval -0.8 to +7.8). Logistic regression was performed controlling for the following parameters: type of sperm, number of previous cycles, and number of babies. In the final model, the variables that significantly predicted the risk of preeclampsia were the type of sperm used for insemination and the number of previous IUI cycles performed. The fewer cycles that were performed, the higher the incidence of preeclampsia that was observed. CONCLUSION(S): IUI with donor sperm appears to increase the incidence of preeclampsia when pregnancy is achieved. A protective effect of multiple cycles appears also to be present in this respect.

Levonorgestrel-releasing intrauterine system vs. endometrial thermal ablation for menorrhagia.

OBJECTIVE: To evaluate the efficacy of a Levonorgestrel-releasing Intrauterine System (LNG-IUS) in controlling menorrhagia in comparison with endometrial thermal rollerball ablation. DESIGN: Seventy-nine consecutive patients with menorrhagia underwent either LNG-IUS insertion (n=42) or hysteroscopical endometrial thermal rollerball ablation (n=37) in a prospective, observational, comparative study. Women reported duration of uterine bleeding in days prior to, and six and 12 months after each intervention. Prior to each intervention, endometrial, cervical or other pathological conditions of the genital tract were excluded. GnRH analogues for endometrial suppression were given for ten weeks before endometrial ablation but not prior to LNG-IUS insertion. RESULTS: There were no differences in duration of uterine bleeding before each intervention in the two groups. The duration of uterine bleeding was lower in the LNG-IUS group as compared with endometrial ablation at six (p<0.001) and 12 months (p<0.001) after each intervention. Furthermore, the effect on reduction of bleeding was stronger in the LNG-IUS group as compared with the endometrial ablation group at six (p<0.001) and 12 months (p<0.001). CONCLUSIONS: The LNG-IUS was more efficacious than endometrial thermal ablation in reducing duration of uterine bleeding at six and 12 months post-intervention.

How to improve the probability of pregnancy in poor responders undergoing in vitro fertilization: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the literature to identify randomized controlled trials, which evaluate interventions aiming to improve the probability of pregnancy in poor responders undergoing in vitro fertilization (IVF). DESIGN: Systematic review and meta-analysis. SETTING: University-based hospital. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy rate. RESULT(S): Twenty-two eligible randomized controlled trials were identified that evaluated in total 15 interventions to increase pregnancy rates in poor responders. Based on limited evidence, the only interventions that appear to increase the probability of pregnancy were the addition of GH to ovarian stimulation (odds ratio for live birth: 5.22, confidence interval: 95% 1.09-24.99) and the performance of embryo transfer on day 2 compared with day 3 (ongoing pregnancy rate: 27.7% vs. 16.3%, respectively; difference: +11.4, 95% confidence interval: +1.6 to +21.0). CONCLUSION(S): Insufficient evidence exists to recommend most of the treatments proposed to improve pregnancy rates in poor responders. Currently, there is some evidence to suggest that addition of GH, as well as performing embryo transfer on day 2 versus day 3, appear to improve the probability of pregnancy.