Adjuvant low-dose aspirin therapy in poor responders undergoing in vitro fertilization: a prospective, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the effect of adjuvant low-dose aspirin on utero-ovarian blood flow and ovarian responsiveness in poor responders undergoing IVF. DESIGN: Prospective randomized, double-blind, placebo-controlled study. SETTING: University-affiliated teaching hospital. PATIENT(S): Sixty patients classified as poor responders undergoing IVF. INTERVENTION(S): Supplementation with low-dose aspirin (80 mg daily) or placebo to a long down-regulation protocol. MAIN OUTCOME MEASURE(S): Doppler measurement of intraovarian and uterine pulsatility index was performed before (baseline) and after ovarian stimulation (day of hCG administration). Duration of use and dose of gonadotropins, cycle cancellation rate, number of mature follicles recruited, and oocytes retrieved were also measured. RESULT(S): High cancellation rates were found in both groups (33.3% vs. 26.7%, placebo vs. treatment). There were no significant differences in total dose of hMG used (66 vs. 57 hMG, 75 IU ampules), median number of mature follicles recruited (3.5 vs. 3.0), or median number of oocytes retrieved (4 vs. 3). No significant differences were found in either intraovarian or uterine artery pulsatility index measured at baseline or on the day of hCG administration. CONCLUSION(S): Supplementation with low-dose aspirin failed to improve either ovarian and uterine blood flow or ovarian responsiveness in poor responders undergoing IVF.

A randomized, double-blind, multiple-dose escalation study of a Chinese herbal medicine preparation (Dang Gui Buxue Tang) for moderate to severe menopausal symptoms and quality of life in postmenopausal women.

OBJECTIVE: This study is a phase II clinical trial that aims to investigate the dose-response relationship of a Chinese herbal medicine preparation, Dang Gui Buxue Tang (DBT), with short-term menopausal symptoms and quality of life in local postmenopausal women. METHODS: A randomized, double-blind, multiple-dose escalation trial was performed in 60 postmenopausal women experiencing severe hot flashes and night sweats. The participants were randomized to receive DBT preparations at 1.5, 3.0, or 6.0 g/day for 12 weeks. The primary outcomes were vasomotor symptoms, Greene Climacteric Scale (GCS) score, and Menopause-Specific Quality of Life (MENQOL) score. Secondary outcomes included serum hormones and lipids. RESULTS: There were between-group differences in psychological/psychosocial (P = 0.015, GCS; P = 0.013, MENQOL) and somatic/physical (P = 0.019, GCS; P = 0.037, MENQOL) domains, and improvement was significantly greatest (P < 0.05) in the 6.0 g/day dose group. The frequency and severity of hot flashes and night sweats were significantly reduced in the 3.0 g/day (14.5%-21.2%, P < 0.05, hot flashes; 28.6%-39.6%, P < 0.05, night sweats) and 6.0 g/day (34.9%-37.4.0%, P < 0.01, hot flashes; 10.1%-12.8%, P < 0.01, night sweats) dose groups. The female hormones follicle-stimulating hormone, luteinizing hormone, and 17ß-estradiol, as well as the lipids total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, were not significantly different within groups and between groups. CONCLUSIONS: DBT preparations at 6.0 g/day significantly improve physical and psychological scores and significantly reduce vasomotor symptoms from baseline. The treatment was well tolerated, with no serious adverse events noted during the 12-week intervention period. The changes do not affect hormones and lipid profiles.

The reproductive and metabolic effect of rosiglitazone on Chinese women with polycystic ovarian syndrome--a double-blind randomized placebo-controlled study.

OBJECTIVE: To investigate whether an insulin sensitizer has any effect on amenorrhea and clinical and biochemical hyperandrogenism in Chinese women with polycystic ovarian syndrome (PCOS). DESIGN: Randomized controlled double-blind trial. SETTING: A tertiary referral center, Hong Kong. PATIENT(S): Chinese women who fulfilled the Rotterdam criteria of PCOS (n = 70). INTERVENTION(S): Rosiglitazone 4 mg daily for the first month followed by 4 mg twice daily for 11 months. MAIN OUTCOME MEASURE(S): Menstrual status as well as clinical and biochemical hyperandrogenism. RESULT(S): There is a significantly higher rate of regular menses among the treatment arm (16 [50.0%] of 32 vs 4 [11.8%] of 34) at 6 months and the improvement appeared to be sustained (10 [41.7%] of 24 vs 6 [20.0%] of 30) at 12 months. There was no change in the acne and hirsutism scores as well as serum T levels in both arms. CONCLUSION(S): We found a possible benefit in menstrual cyclicity but a lack of improvement in hyperandrogenism in our Chinese population. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-09000670 (Chinese Clinical Trial Registry).

Comprehensive assessment of serum estradiol impact on selected physiologic markers observed during in-vitro fertilization and embryo transfer cycles.

OBJECTIVE: This investigation assessed the effect of serum estradiol levels on outcomes of in-vitro fertilization and embryo transfer (IVF) cycles. MATERIALS AND METHOD: This was a retrospective cohort study of 1123 IVF cycles comparing impact of estradiol (E(2)) levels on follicular development, fertilization, embryo quality, implantation, pregnancy rate, miscarriage rate, and selected obstetric complications. RESULTS: We found high serum E(2) levels to be significantly associated with increased number of mature follicles and mature oocytes retrieved (p<0.01, for both). E(2) levels were also associated with more viable and good-quality embryos (p<0.01). There was no significant impact of E(2) on oocyte maturation, fertilization rate, embryo quality, or overall pregnancy rates. Moreover, high E(2) levels were significantly associated with higher implantation rates and reduced incidence of miscarriage (p<0.05, for both). CONCLUSION: Within the safety range in clinical practice, our data demonstrate a generally positive effect of high serum E(2) on selected IVF parameters.

Birth of a healthy baby after transfer of blastocysts derived from cryopreserved human oocytes fertilized with frozen spermatozoa.

OBJECTIVE: To report the birth of a healthy baby after transfer of blastocysts derived from frozen eggs and frozen spermatozoa. DESIGN: Case report. SETTING: University-based assisted reproduction center. PATIENT(S): A 37-year-old woman with secondary infertility of 4 years' duration. INTERVENTION(S): Retrieved oocytes were cryopreserved in 1.5 M 1,2-propanediol (PROH) and 0.3 M sucrose by a slow freezing-rapid thawing protocol, semen cryopreservation, and insemination by intracytoplasmic sperm injection (ICSI) at 4 hours after thawing. MAIN OUTCOME MEASURE(S): Fertilization and embryo development to blastocyst stage, pregnancy, and outcome. RESULT(S): Ten of 14 frozen oocytes survived after thawing. Eight of them were fertilized by performing ICSI and three developed into 7- to 8-cell embryos on day 3. Two of these embryos developed into blastocysts on day 5 and were transferred. This resulted in a successful pregnancy and the delivery of a healthy baby boy. CONCLUSION(S): This case demonstrates the feasibility of inseminating the frozen-thawed human oocytes after 4 hours of in vitro culture and the zygotes derived from frozen oocytes and frozen spermatozoa can be cultured to blastocysts resulting in the live birth of a healthy baby boy.

GnRH antagonist versus long GnRH agonist protocol in poor responders undergoing IVF: a randomized controlled trial.

BACKGROUND: This is the first published report of a prospective, randomized, controlled trial comparing a fixed, multi-dose GnRH antagonist protocol with a long GnRH agonist protocol in poor responders undergoing IVF. METHODS: Sixty-six poor responders were randomized into two groups: the study group received 0.25 mg of cetrorelix daily starting on day 6 of stimulation; the control group received 600 microg of buserelin acetate daily starting in the mid-luteal phase of the preceding cycle. Both groups were given a fixed dose of recombinant FSH (300 IU daily) for stimulation. RESULTS: There were no significant differences in the cycle cancellation rates, duration of stimulation, consumption of gonadotrophins, and mean numbers of mature follicles, oocytes and embryos obtained. The implantation rates were similar, but the number of embryos transferred was significantly higher for the antagonist group (2.32 +/- 0.58 versus 1.50 +/- 0.83; P = 0.01). The pregnancy rates were also higher in the antagonist group, but the difference was not statistically significant. CONCLUSION: A fixed multi-dose GnRH antagonist protocol is feasible for patients who are poor responders on a long agonist protocol; however, our study failed to demonstrate an overall improvement in ovarian responsiveness. Clinical outcomes may be improved by developing more flexible antagonist regimens, an approach that requires further evaluation.

Accuracy of clinical diagnostic methods of threatened abortion.

OBJECTIVE: To examine the accuracy of clinical diagnostic methods in assessing vaginal bleeding in pregnant women before 28 weeks' gestation. METHODS: 772 consecutive women who presented with threatened abortion before 28 weeks' gestation were studied. Structured history and physical examination were performed on each woman as initial clinical assessment. This was followed by transvaginal sonography to determine the status of pregnancy. The accuracy of diagnoses at different clinical stages (history, physical examination, and transvaginal sonography) relative to the final diagnosis was compared using the kappa coefficient (kappa). RESULTS: Clinicians were unable to accurately diagnose or predict the status of the pregnancy from history alone (kappa = 0.33; 95% CI 0.28, 0.38) or after physical examination (kappa = 0.57; 95% CI 0.52, 0.62). Transvaginal sonography led to an accurate diagnosis of pregnancy status (kappa = 0.96; 95% CI 0.95, 0.98) in most cases, except where an ectopic pregnancy existed. Absence of abdominal tenderness (p = 0.04), cervical excitation (p = 0.02), and incorrect identification of retained products of conception on transvaginal sonography (p = 0.01) were features of missed ectopic pregnancy. CONCLUSIONS: The clinical assessment of threatened abortion by history and physical examination is unreliable in most cases. The diagnostic accuracy is improved by the addition of transvaginal sonography. Even with the help of transvaginal sonography, a small proportion of ectopic pregnancies will be missed.

Psychiatric morbidity amongst infertile Chinese women undergoing treatment with assisted reproductive technology and the impact of treatment failure.

This is a prospective study to assess the psychiatric morbidity in Chinese infertile women who underwent treatments with assisted reproductive technology and also the impact of treatment failure. The 30-item General Health Questionnaire (GHQ) and the Beck Depression Inventory (BDI) were employed before and 3 weeks after the assisted reproductive technology treatment. Data from 372 patients who completed the questionnaires and failed the treatment were analyzed. Before treatment, 33% of the participants scored above the GHQ cutoff, and 8% had a BDI score of 20 or above, signifying moderate to severe depression. Following failed treatment, 43% scored above GHQ cutoff, and 8% had BDI scores 20 or above. The posttreatment GHQ and BDI scores were significantly higher than the corresponding scores at baseline (p < 0.001). About 13% of the participants reported self-harm ideas. The severity of depression following a failed treatment was positively associated with the duration of infertility (p < 0.05), but not with the posttreatment BDI scores, age, education, and number of previous treatment episodes. Our results show that one third of the women who sought infertility treatment had an impaired psychological well-being. Following failed treatment, there was a further deterioration in mental health, and about 10% of the participants were moderately to severely depressed. Proper psychological care and counseling should be an integral part of infertility management among the Chinese population.