Bih Chwen Hsieh

Comparison of outcome of clomiphene citrate/human menopausal gonadotropin/cetrorelix protocol and buserelin long protocol – a randomized study

This study evaluates the efficacy of a stimulation protocol with clomiphene citrate (CC)/human menopausal gonadotropin (hMG)/cetrorelix and its effects on oocyte quality and endometrium. One hundred and twenty couples with male-factor infertility who were about to undergo their first intracytoplasmic sperm injection cycles were randomized into two groups. Sixty women were stimulated with the CC/hMG/cetrorelix protocol (cetrorelix group) and 60 received the buserelin long protocol (buserelin group). Fewer oocytes were recovered in the cetrorelix group than in the buserelin group (mean ± standard deviation (SD): 11.1 ± 4.0 vs. 17.3 ± 5.8, p < 0.001); however, the percentages of metaphase II, metaphase I and germinal vesicle oocytes were similar between the two groups. Serum estradiol level was significantly lower in the cetrorelix than in the buserelin group (mean ± SD: 2600.58 ± 1189.11 vs. 3293.46 ± 1221.49 pg/ml, p = 0.006), but the endometrial thickness was similar. The implantation rates (19.2% vs. 17.7%) and the pregnancy rates (41.7% vs. 40.0%) were similar between groups. The ampoules (mean ± SD: 18.9 ± 3.0 vs. 38.9 ± 12.2, p < 0.001) and injections (mean ± SD: 6.8 ± 1.1 vs. 15.7 ± 3.1, p < 0.001) of gonadotropin used were significantly lower in the cetrorelix group than in the buserelin group. No patients in either group developed a premature luteinizing hormone surge. The present study found no statistically significant difference between the two treatment modalities with regard to pregnancy rates.

Laminaria tent vs misoprostol for cervical priming before hysteroscopy: Randomized study.

STUDY OBJECTIVE To compare the efficacy of laminaria tents and orally administered misoprostol in priming the cervix before operative hysteroscopy. DESIGN Randomized, controlled study (Canadian Task Force classification I). SETTING Tertiary medical center. PATIENTS One hundred twenty premenopausal women who underwent operative hysteroscopy between March 2005 and January 2007. INTERVENTION The women were randomized to receive a laminaria tent or misoprostol for cervical priming. MEASUREMENTS AND MAIN RESULTS The primary outcomes were postpriming cervical width insofar as size of Hegar dilators and need for cervical dilation. The secondary outcomes were adverse effects from the priming methods. Postpriming cervical width was greater in the laminaria group but not significantly different from that in the misoprostol group. However, cervical dilation before hysteroscopy was required in more patients in the misoprostol group. Nausea, vomiting, diarrhea, and bleeding were more common in the misoprostol group, and the incidences of chills and headache were similar between the 2 groups. CONCLUSION Laminaria tents are superior to oral misoprostol insofar as less need for cervical dilation and fewer adverse effects.

Clinical outcome according to timing of cabergoline initiation for prevention of OHSS: a randomized controlled trial

Cabergoline, a dopamine receptor-2 agonist, is suggested to prevent ovarian hyperstimulation syndrome (OHSS) during ovarian stimulation. The aim of this study was to evaluate the influence of different timing of cabergoline administration on clinical outcome among patients at risk of developing OHSS. Among infertile women undergoing IVF treatment at risk of developing OHSS, 206 were enrolled in this study. The subjects were randomly allocated into two groups, i.e. the study group (n=100) receiving cabergoline beginning on the day of human chorionic gonadotrophin (HCG) injection and the control group (n=100) receiving cabergoline starting on the day of oocyte retrieval. Oocyte metaphase-II rate, fertilization rate, clinical outcome and incidence of severe OHSS were compared between the two groups. There were no significant differences in oocyte metaphase-II rate (0.86 ± 0.16 versus 0.85 ± 0.15) or fertilization rate (0.79 ± 0.22 versus 0.76 ± 0.20) or in the incidence of OHSS between two groups. Similarly, there were no significant differences in implantation or clinical pregnancy rate between the two groups. Cabergoline can be administered as soon as HCG injection to prevent early OHSS, without adverse effects on oocyte maturation, fertilization rate and clinical outcome.

Subtle progesterone rise in the single-dose gonadotropin-releasing hormone antagonist (cetrorelix) stimulation protocol in patients undergoing in vitro fertilization or intracytoplasmic sperm injection cycles

A subtle rise in serum progesterone during the late follicular phase in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles is a frequent event that can decrease implantation and pregnancy rates in controlled ovarian hyperstimulation (COH) protocols that use a gonadotropin-releasing hormone (GnRH) antagonist. The aim of the present study was to evaluate the prevalence and effect of the subtle progesterone rise during COH with single-dose GnRH antagonist in combination with clomiphene citrate (CC) and human menopausal gonadotropins (hMG) in IVF or ICSI cycles. Ninety-five women undergoing COH with CC, hMG and a single 2.5 mg dose of the GnRH antagonist, cetrorelix, were enrolled in the study. Patients were grouped according to serum progesterone level on the day of human chorionic gonadotropin (hCG) administration (P < 1.2 ng/ml or P ≥ 1.2 ng/ml). The incidence of a subtle progesterone rise was 54.7% (52/95). The group with P ≥ 1.2 ng/ml had significantly higher serum levels of luteinizing hormone (p = 0.002) and estradiol (p < 0.001) on the day of hCG injection than the group with P < 1.2 ng/ml, and more oocytes were retrieved (p = 0.001). However, there was no significant difference in fertilization, clinical pregnancy or implantation rate between the two groups. In conclusion, a subtle progesterone rise during the late follicular phase is common but not associated with pregnancy outcome.

Characteristics of progesterone changes in women with subtle progesterone rise in recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonist cycle

Background: To assess the characteristics of progesterone (Prog) changes in women with a subtle Prog rise in recombinant follicle-stimulating hormone (r-FSH) and GnRH antagonist cycles. Methods: We enrolled 233 patients undergoing controlled ovarian hyperstimulation with r-FSH and GnRH antagonist for IVF or ICSI. A subtle Prog rise 1 day before hCG administration was defined as a Prog value of ≧1.2 ng/ml. Results: 100 of 233 cycles (42.9%) showed a subtle Prog rise in this study. The mean serum Prog levels and area under curve (AUC) in the group with Prog ≧1.2 ng/ml was significantly higher than that in the Prog <1.2 ng/ml group on cycle day 8 (1.17 ± 0.4 and 0.80 ± 0.3 ng/ml, respectively, for Prog level, p = 0.003; 571 ± 123 and 763 ± 250 for AUC, p = 0.001), and remained significantly higher until the day of hCG administration. Moreover, 55% of the patients on cycle day 9, 65% on cycle day 10, 75% on cycle day 11 and 85% on cycle day 12 in the Prog ≧1.2 ng/ml group have a serum Prog level of ≧1.2 ng/ml. Conclusion: A subtle Prog rise may occur as early as cycle day 8 in r-FSH/GnRH antagonist cycles.

Effect of a lower‐dose cetrorelix acetate protocol on in‐vitro fertilization outcome

To determine whether a low initial dosage of cetrorelix acetate could prevent a premature luteinizing hormone (LH) surge in women undergoing controlled ovarian stimulation.

Bacterial colonization with balloon uterine stent placement in the uterus for 30 days: a randomized controlled clinical trial

OBJECTIVE To assess bacterial colonization following balloon uterine stent placement in the uterus for 30 days. DESIGN Prospective randomized controlled study. SETTING Tertiary medical center. PATIENT(S) Sixty-eight women scheduled for hysteroscopy. INTERVENTION(S) Women who were undergoing hysteroscopic surgery were randomly assigned to receive a balloon uterine stent or not. Before starting surgery, the uterine cavity was swabbed for bacterial culture. The device was placed in the uterus after surgery in the stent group. After 30 days, the stent was removed and sent for culture and the uterine cavity also swabbed and cultured. The uterine cavities of the control patients were swabbed before and 30 days after surgery. MAIN OUTCOME MEASURE(S) The primary outcome was the incidence of bacterial colonization of the uterus. Secondary outcomes were pain intensity and species of colonizing bacteria. RESULT(S) Excluding eight women, 30 women in each group were included in this analysis. In the stent group, three women (10.0%) demonstrated bacterial colonization before surgery compared with nine women (30.0%) after 30 days. In the control group, four (13.3%) and ten (33.3%) women had microorganisms detected in the uterus before and after 30 days after surgery, respectively. In neither group did the percentage of women with uterine microorganisms increase significantly after 30 days. The percentages of women with uterine bacterial colonization before and 30 days after surgery were similar between both groups. CONCLUSION(S) Balloon uterine stents may be placed after surgery for up to 30 days without increasing bacterial colonization. CLINICAL TRIAL REGISTRATION NUMBER ClinicalTrials.gov (www.clinicaltrials.gov) NCT01167296.

Safety and efficacy of mixing cetrorelix with follitropin alfa: a randomized study

OBJECTIVE To assess the safety and efficacy of mixing cetrorelix with follitropin alfa (rFSH) in assisted reproductive technology. DESIGN Prospective, randomized study. SETTING An IVF center in a teaching hospital. PATIENT(S) One hundred forty patients undergoing intracytoplasmic sperm injection were randomized into mixed (M) or separate (S) injection groups. INTERVENTION(S) In the M group, rFSH and cetrorelix were mixed immediately before administration, whereas in the S group, rFSH and cetrorelix were administered separately. MAIN OUTCOME MEASURE(S) The primary efficacy end point was the incidence of premature LH surge. The secondary efficacy endpoints included estradiol levels on the day of hCG injection, numbers of oocytes obtained, implantation, and ongoing pregnancy rates. The safety endpoints included ovarian hyperstimulation syndrome, and adverse events related to injections including local tolerability. RESULT(S) Excluding eight patients who dropped out of the study, there were 66 patients in each group for analysis. Patients in the M group received significantly fewer injections than patients in the S group (9.1 vs. 13.9). Other outcome parameters, including incidences of premature LH surge, numbers of oocytes retrieved, fertilization, implantation, and ongoing pregnancy rates were similar between the two groups. CONCLUSION(S) Cetrorelix and rFSH can be mixed together without compromising their reported safety and efficacy. This observation is in line with the reported safety and efficacy profile of the products listed in their current package inserts.

Effect of incubation with different concentrations and durations of FSH for in-vitro maturation of murine oocytes

The purpose of the study was to evaluate whether a lower concentration of FSH or 2-h incubation with FSH would improve the outcome of in-vitro maturation of oocytes. The immature oocytes were obtained from FVB mice, and were allocated to four groups and incubated in the maturation media for 24 h. The maturation media were supplemented with 10 mIU/ml FSH for 24 h (group 1), 10 mIU/ml FSH for 2 h (group 2), 75 mIU/ml FSH for 24 h (group 3) or 75 mIU/ml FSH for 2 h (group 4). In each group, half of the in-vitro-matured oocytes were fertilized and cultured to blastocysts and the remaining matured oocytes were analysed for growth differentiation factor (GDF)-9 and bone morphogenetic protein (BMP)-15 mRNA to assess the oocyte quality. The maturation rates and oocyte BMP-15 mRNA concentrations were similar among the four groups. The GDF-9 mRNA concentrations were similar in group 2 and group 4. The fertilization and blastocyst rates were higher in groups 2 and 4 than in groups 1 and 3. It is concluded that 2-h incubation with FSH is better than 24-h incubation in terms of the fertilization rate and blastocyst development.

Conservative treatment of cervico-isthmic heterotopic pregnancy by fine needle aspiration for selective embryo reduction

An unusual case of a heterotopic cervico-isthmic pregnancy after IVF treatment occurred in a 34-year-old woman. Transvaginal ultrasound-guided aspiration of the gestational sac for embryo reduction was safely used to manage the pregnancy and preserve the intrauterine fetus.