Ernest Hung Yu Ng

Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial

BACKGROUND A single 10 mg dose of mifepristone, and two 0.75 mg doses of levonorgestrel 12 h apart, are effective for emergency contraception. Because no studies had compared the efficacies of both compounds, or investigated a single dose of 1.5 mg levonorgestrel, we undertook this three-arm trial. METHODS We did a randomised, double-blind trial in 15 family-planning clinics in 10 countries. We randomly assigned 4136 healthy women with regular menstrual cycles, who requested emergency contraception within 120 h of one unprotected coitus, to one of three regimens: 10 mg single-dose mifepristone; 1.5 mg single-dose levonorgestrel; or two doses of 0.75 mg levonorgestrel given 12 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Analysis was by intention to treat, but we did exclude some patients from the final analyses. FINDINGS Of 4071 women with known outcome, pregnancy rates were 1.5% (21/1359) in those given mifepristone, 1.5% (20/1356) in those assigned single-dose levonorgestrel, and 1.8% (24/1356) in women assigned two-dose levonorgestrel. These proportions did not differ significantly (p=0.83). The relative risk of pregnancy for single-dose levonorgestrel compared with two-dose levonorgestrel was 0.83 (95% CI 0.46-1.50), and that for levonorgestrel (the two regimens combined) compared with mifepristone, 1.05 (0.63-1.76). Side-effects were mild and did not differ greatly between groups, and most women menstruated within 2 days of the expected date. Women who took levonorgestrel had earlier menses than did those who took mifepristone. INTERPRETATION The three regimens studied are very efficacious for emergency contraception and prevent a high proportion of pregnancies if taken within 5 days of unprotected coitus. Mifepristone and levonorgestrel do not differ in efficacy. A 1.5 mg single levonorgestrel dose can substitute two 0.75 mg doses 12 h apart.

A randomized double blind comparison of real and placebo acupuncture in IVF treatment.

BACKGROUND Acupuncture has been used during IVF treatment as it may improve outcome, however, there are concerns about the true efficacy of this approach. This randomized double blind study aimed to compare real acupuncture with placebo acupuncture in patients undergoing IVF treatment. METHODS On the day of embryo transfer (ET), 370 patients were randomly allocated to either real or placebo acupuncture according to a computer-generated randomization list in sealed opaque envelopes. They received 25 min of real or placebo acupuncture before and after ET. The endometrial and subendometrial vascularity, serum cortisol concentration and the anxiety level were evaluated before and after real and placebo acupuncture. RESULTS The overall pregnancy rate was significantly higher in the placebo acupuncture group than that in the real acupuncture group (55.1 versus 43.8%, respectively, P = 0.038; Common odds ratio 1.578 95% confidence interval 1.047-2.378). No significant differences were found in rates of ongoing pregnancy and live birth between the two groups. Reduction of endometrial and subendometrial vascularity, serum cortisol concentration and the anxiety level were observed following both real and placebo acupuncture, although there were no significant differences in the changes in all these indices between the two groups. CONCLUSIONS Placebo acupuncture was associated with a significantly higher overall pregnancy rate when compared with real acupuncture. Placebo acupuncture may not be inert. Trial registered with HKClinicalTrials.com: number HKCTR-236.

The role of acupuncture in the management of subfertility

OBJECTIVE To review systematically the use of acupuncture in the management of subfertility. DESIGN A computer search was performed via several English and Chinese databases to identify journals relevant to the subject. RESULT(S) The positive effect of acupuncture in the treatment of subfertility may be related to the central sympathetic inhibition by the endorphin system, the change in uterine blood flow and motility, and stress reduction. Acupuncture may help restore ovulation in patients with polycystic ovary syndrome, although there are not enough randomized studies to validate this. There is also no sufficient evidence supporting the role of acupuncture in male subfertility, as most of the studies are uncontrolled case reports or case series in which the sample sizes were small. Despite these deficiencies, acupuncture can be considered as an effective alternative for pain relief during oocyte retrieval in patients who cannot tolerate side effects of conscious sedation. The pregnancy rate of IVF treatment is significantly increased, especially when acupuncture is administered on the day of embryo transfer. CONCLUSION(S) Although acupuncture has gained increasing popularity in the management of subfertility, its effectiveness has remained controversial.

Effects of chinese green tea on weight, and hormonal and biochemical profiles in obese patients with polycystic ovary syndrome : A randomized placebo-controlled trial

Objectives: To study the effects of green tea on body weight, and biochemical and hormonal profiles in obese Chinese women with polycystic ovary syndrome (PCOS). Methods: Thirty-four obese Chinese women with PCOS were randomized into either treatment with green tea capsules or placebo for 3 months. The anthropomentric measurements, and biochemical and hormonal profiles before and after treatment in each group were compared. Results: The body weight of the green tea group decreased by a nonsignificant 2.4% after treatment; whereas the body weight, body mass index (BMI), and body fat content of the control group were significantly higher after 3 months. There were no differences in any of the hormone levels measured in either group. The biochemical profiles of the two groups were also similar except that there was a small but significant rise in the triglyceride level in the green tea group. Fewer patients in the green tea group remained amenorrhoeic, but this was not significantly different from the control group. Conclusions: Green tea supplementation did not significantly reduce body weight in obese women with PCOS, nor did it alter the glucose or lipid metabolism.

Gene expression profiling of human peri-implantation endometria between natural and stimulated cycles

OBJECTIVE To investigate the effect of high serum E(2) levels in gonadotropin-stimulated cycles (hCG+7) on the gene expression patterns of human endometrium compared with natural cycles on the seventh day of LH surge (LH+7) and elucidate the underlying molecular changes that may be related to endometrial receptivity. DESIGN Observational study. SETTING University Hospital. PATIENTS(S) Infertile patients with normal menstrual cycles undergoing IVF treatment. INTERVENTION(S) Gonadotropin stimulation and endometrial biopsy. MAIN OUTCOME MEASURE(S) Gene expression by microarray and quantitative polymerase chain reaction (qPCR). RESULT(S) Endometrial samples from natural (n = 5) and stimulated (n = 8) cycles were collected. Patients in the stimulated cycles were classified as moderate (n = 4) or excessive (n = 4) responders if their serum E(2) levels on the day of administration of hCG were <or=20,000 pmol/L or >20,000 pmol/L, respectively. The RNA transcripts were profiled by Affymetrix HG-U133A microarray. Clustering and principal component analysis demonstrated a significant difference (>or=2-fold) in the expression patterns of 411 genes among the three groups. Putative estrogen response elements or progesterone response elements were identified in the promoter regions of 49 differentially expressed genes of diverse biologic functions. The qPCR confirmed the microarray result in 47 endometrial samples. CONCLUSION(S) High serum E(2) and/or progesterone modulate the gene expression profiles of human endometrium and may affect endometrial receptivity.

Glycodelin-A interacts with fucosyltransferase on human sperm plasma membrane to inhibit spermatozoa-zona pellucida binding

Fertilization depends on successful binding of the spermatozoa to the zona pellucida of the oocyte. Glycodelin-A inhibits spermatozoa-zona pellucida binding. Previous data showed that glycodelin-A receptor(s) and zona pellucida protein receptor(s) on human spermatozoa are closely related. Using a chemical cross-linking approach, the glycodelin-A-sperm receptor complex was isolated. The receptor was identified to be fucosyltransferase-5 (FUT5) by mass spectrometry and confirmed with the use of anti-FUT5 antibodies. Sperm FUT5 was an externally oriented integral membrane protein in the acrosomal region of human spermatozoa. Biologically active FUT5 was purified from spermatozoa. Co-immunoprecipitation confirmed the interaction between glycodelin-A and sperm FUT5. Solubilized zona pellucida reduced the binding of glycodelin-A to sperm FUT5. An anti-FUT5 antibody and FUT5 acceptor blocked the binding of glycodelin-A to spermatozoa and the zona binding inhibitory activity of glycodelin-A. Sperm FUT5 bound strongly to intact and solubilized human zona pellucida. The equilibrium dissociation constant of sperm FUT5 binding to solubilized zona pellucida was 42.82 pmol/ml. These observations suggest that human sperm FUT5 is a receptor of glycodelin-A and zona pellucida proteins, and that glycodelin-A inhibits spermatozoa-zona binding by blocking the binding of sperm FUT5 to the zona pellucida.

Excessive ovarian stimulation up-regulates the Wnt-signaling molecule DKK1 in human endometrium and may affect implantation: an in vitro co-culture study

BACKGROUND High serum estradiol (E2) levels following ovarian stimulation lead to reduced implantation and pregnancy rates, yet the underlying mechanisms remain unknown. We investigated if aberrant expression of genes in the Wnt-signaling pathway may be involved. METHODS Microarray and real-time PCR analysis were performed to analyze gene expression profiles of endometrial samples taken at day hCG + 7 in stimulated cycles, and days LH + 7 and LH + 10 in natural cycles. Expression of several Wnt-signaling transcripts, including Dickkopf homolog 1 (DKK1), DKK2 and secreted frizzled-related protein 4 (sFRP4), was analyzed throughout the menstrual cycle. JAr spheroid/Ishikawa endometrial cell co-culture experiments were established to study effects of DKK1 on spheroid attachment in vitro. RESULTS We identified 351 differentially expressed genes. Endometrial samples taken at hCG + 7 had similar expression profiles to those at LH + 10. DKK1 transcripts were up-regulated and DKK2 and sFRP4 were down-regulated in the stimulated compared with LH + 7 group (all P < 0.05). DKK1 transcripts were low in proliferative phase (PS) and increased in late-secretory phase (LS, P < 0.05), although DKK2 peaked in mid-secretory phase (P < 0.05). sFRP4 transcripts were high in PS. Treatment of spheroid with recombinant human DKK-1 protein dose-dependently suppressed (P < 0.05 versus control) spheroids attachment onto endometrial cells (associated with decreased beta-catenin protein): this suppression was nullified by anti-DKK1 antibody. CONCLUSION Gene expression patterns in stimulated cycles resembled those of LS in natural cycles, when the implantation window is about to close, suggesting high serum E2 and/or progesterone concentrations may advance endometrial development, altering the implantation window and possibly decreasing pregnancy rate. Aberrant expression of DKK1 might impair embryo attachment and implantation in vivo.

Serum anti-müllerian hormone level is not altered in women using hormonal contraceptives

BACKGROUND Anti-müllerian hormone (AMH) is secreted from granulosa cells of antral follicles into the circulation of adult women and hence could serve as an ovarian function test. This would be of value to hormonal contraceptive users if its serum level is unaffected by the use of hormonal contraceptives. STUDY DESIGN We prospectively recruited 95 women using combined oral contraceptive (n=23), combined injectable contraceptive (n=23), progestogen-only pills (n=9), progestogen-only injectable (n=20) and levonorgestrel intrauterine system (n=20), and measured their serum AMH concentration before and 3-4 months after treatment. RESULTS No significant difference in pre- and post-treatment serum AMH level was evident in all the treatment groups studied. CONCLUSIONS Being unaffected by hormonal contraceptives, serum AMH measurement is potentially a useful clinical test in hormonal contraceptive users for the differential diagnosis of anovulatory disorders and determination of menopause.

Correlation between three assay systems for anti-Müllerian hormone (AMH) determination

PurposeAnalysis of anti-Müllerian hormone (AMH) is becoming of recognized importance in reproductive medicine, but assays are not standardized. We have evaluated the correlation between the new Gen II ELISA kit (Beckman-Coutler) and the older ELISA kits by Immunotech (IOT) and Diagnostic Systems Laboratories (DSL).MethodsA total of 56 archived serum samples from patients with subfertility or reproductive endocrine disorders were retrieved and assayed in duplicate using the three AMH ELISA kits . The samples covered a wide range of AMH concentrations (1.9 to 142.5 pmol/L).ResultsWe observed good correlations between the new (AMH Gen II) and old AMH assay kits by IOT and DSL (R2 = 0.971 and 0.930 respectively). The regression equations were AMH (Gen II) = 1.353 × AMH (IOT) + 0.051 and AMH (Gen II) = 1.223 × AMH (DSL) – 1.270 respectively.ConclusionsAMH concentrations using the Gen II kit are slightly higher than those from the IOT and DSL kits. Standardization of assay results worldwide is urgently required but this analysis facilitates the interpretation of values obtained historically and in future studies using any of the 3 assays available. Meanwhile, adapting clinical cut-offs from previously published work by direct conversion is not recommended.

Gender Selection in China: Its Meanings and Implications

With the advancement of assisted reproduction technologies, people are offered wider choices to choose the gender of their offspring and to construct ‘ideal-typed’ families with specific gender structure. Gender selection is welcomed by many societies with gender-specific preference, especially those patriarchal societies such as Chinese communities. It is not only a medical procedure but also a social orientation, which reveals much of the underlying preference towards gender. This paper explores the cultural dimensions to gender selection and its psychosocial meanings and implications in Chinese societies, especially after the establishment of One Child Policy in China. Problems associated with son preference in the culture with strong gender stereotyping are addressed. We believe that gender selection for social reasons should not be allowed since undesirable outcomes will be resulted under such strict population control program.