A prospective double-blinded, randomized, placebo-controlled trial on the use of letrozole pretreatment with misoprostol for second-trimester medical abortion.

BACKGROUND: The aim of this randomized trial was to evaluate the abortion rate of combined regimen of letrozole and misoprostol in second-trimester abortion. STUDY DESIGN: This was a randomized, double-blinded, placebo-controlled trial of 130 women requesting legal termination of pregnancy at gestational age between 12 and 20 weeks. Letrozole 7.5 mg or placebo were given for 3 days, followed by misoprostol 400 mcg vaginally every 3 h up to a maximum of five doses on the third day. RESULTS: The abortion rate in 24 and 48 h were similar for the letrozole and placebo groups (24 h: 93.8% vs. 90.8%, respectively, p=.718; 48 h: 98.5% vs. 95.4%, respectively, p=.496). The median induction-to-abortion interval was also similar for the letrozole and placebo groups (9.6 h vs. 10.6 h, p=.145). All the side effects were comparable between the two groups. CONCLUSION: The use of letrozole pretreatment (7.5 mg daily for 3 days) with misoprostol in second-trimester abortion does not significantly improve the abortion rate of the misoprostol-only regimen.

Pharmacokinetics of repeated doses of misoprostol.

BACKGROUND: Misoprostol is widely used in obstetrics and gynaecology for medical abortion, cervical priming and induction of labour. To aid the design of effective and safe regimens, we have investigated the pharmacokinetic parameters after the vaginal or sublingual administration of repeated doses of 400 microg of misoprostol. METHODS: Women undergoing termination of pregnancy by suction evacuation were randomized to receive 400 microg of sublingual or vaginal misoprostol every 3 h for five doses. Venous blood was taken at 180, 200, 240, 360, 380, 420, 540, 560, 600, 720, 740, 780 and 900 min after the first dose of misoprostol for determination of the plasma level of misoprostol acid (MPA). RESULTS: The peak plasma levels of MPA decreased with successive doses of vaginal misoprostol, whereas the peak plasma levels were similar with successive doses of sublingual misoprostol. After the third dose, the peak plasma levels of MPA after sublingual misoprostol were significantly higher than those after vaginal administration. After the final dose, the area under the MPA concentration-time curve after sublingual administration was significantly higher than that after vaginal misoprostol (P < 0.031). However, subgroup analysis in the vaginal administration group showed that the progressive decline in the peak plasma levels of MPA occurred only in women with significant vaginal bleeding. CONCLUSIONS: The peak plasma level of MPA after each dose of misoprostol is higher and the bioavailability is also greater after sublingual administration, compared with that after vaginal administration, of repeated doses of misoprostol. The difference was probably due to the reduction in absorption of vaginal misoprostol in the presence of significant vaginal bleeding.

Changes in endometrial and subendometrial blood flow in IVF.

A good blood supply to the endometrium is usually considered as an essential requirement for implantation. Endometrial and subendometrial blood flow was evaluated on the days of human chorionic gonadotrophin (HCG) administration and embryo transfer and the percentage change in endometrial and subendometrial blood flow between these 2 days was assessed as a predictor of pregnancy during IVF treatment. A three-dimensional (3D) ultrasound examination with power Doppler was performed in 293 patients undergoing the first IVF cycle to determine endometrial thickness, endometrial volume, vascularization index, flow index and vascularization flow index of endometrial and subendometrial regions on the days of HCG and embryo transfer. Patients in non-pregnant and pregnant groups had comparable endometrial thickness, endometrial volume and 3D power Doppler flow indices of endometrial and subendometrial regions measured on either day. Percentage changes in endometrial and subendometrial 3D power Doppler flow indices were also similar. In conclusion, endometrial and subendometrial blood flow on the days of HCG and embryo transfer and the percentage change in endometrial and subendometrial blood flows between these 2 days were not predictive of pregnancy in IVF treatment.

Ovarian stromal blood flow following clomiphene citrate challenge test in infertile women.

PURPOSE: To compare ovarian stromal blood flow indices in the follicular phase and after clomiphene citrate (CC) in infertile women. METHODS: Pulsatility index (PI), resistance index (RI), and peak systolic blood flow velocity (PSV) of ovarian stromal vessels were determined by spectral Doppler analysis in the early follicular phase and on day 10 after CC. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol concentrations were determined. RESULTS: A total of 69 infertile women were included in the analysis. No significant differences in the average PI, RI, and PSV of ovarian stromal blood flow were demonstrated in the follicular phase and after CC despite a significant increase in serum estradiol concentration after CC. Serum FSH concentration was similar in the follicular phase and after CC, while serum LH concentration was significantly higher after CC. In the right ovary, ovarian stromal blood flow was absent in 13 (18.8%) patients in the follicular phase and in 6 (8.7%) patients after CC, but the difference did not reach statistical significance. In the left ovary, ovarian stromal blood flow was absent in 13 (18.8%) and 12 (17.4%) patients in the follicular phase and after CC, respectively. CONCLUSION: Ovarian stromal blood flow indices were similar in the follicular phase and after CC.

Randomized double-blind comparison of laser zona pellucida thinning and breaching in frozen-thawed embryo transfer at the cleavage stage.

OBJECTIVE: To compare the implantation and ongoing pregnancy rates of frozen-thawed embryo transfer (FET) using laser thinning with those of laser breaching of the zona pellucida (ZP). DESIGN: Double-blind randomized study. SETTING: A tertiary assisted reproduction unit. PATIENT(S): Infertile patients undergoing FET cycles. INTERVENTION(S): In the thinning group, more than a quarter of the ZP's outer half-diameter was removed by using a 1,480-nm noncontact laser, whereas a hole about 30 microm in size was created in the ZP in the breaching group. MAIN OUTCOME MEASURE(S): Implantation and ongoing pregnancy rates. RESULT(S): On the day of the FET, 180 patients were randomly divided into the thinning and breaching groups according to a computer-generated randomization list that was placed in sealed envelopes. The two groups were comparable in terms of demographic characteristics, ovarian response of the stimulated cycle, and quality of fresh and frozen-thawed embryos. The implantation and ongoing pregnancy rates of the thinning group were significantly higher than the corresponding rates of the breaching group but were similar to those of patients without ZP thinning or breaching. CONCLUSION(S): Laser ZP thinning is associated with significantly higher implantation and ongoing pregnancy rates in FET cycles compared with the case of laser ZP breaching.

The role of endometrial blood flow measured by three-dimensional power Doppler ultrasound in the prediction of pregnancy during in vitro fertilization treatment.

Ultrasound examination of the endometrium is a commonly used non-invasive method to assess endometrial receptivity during in vitro fertilization (IVF) treatment. A good blood supply towards the endometrium is usually considered to be an essential requirement for implantation and therefore assessment of endometrial blood flow in IVF treatment has attracted a lot of attention in recent years. Doppler study of uterine arteries does not reflect the actual blood flow to the endometrium. Endometrial and subendometrial blood flows can be more objectively and reliably measured with three-dimensional power Doppler ultrasound. However, conflicting results are reported with regard to their role in the prediction of pregnancy in IVF treatment. Relevant studies in the literature differed in patients' characteristics, the day of ultrasound examination and the selection of the subendometrial region. As the degree of change in endometrial perfusion from the late follicular phase to the early luteal phase may be a more important determinant of endometrial receptivity, further studies should be conducted to determine the change in endometrial and subendometrial blood flows from late follicular phase to early luteal phase in order to delineate the role of endometrial and subendometrial blood flows in predicting IVF outcome.

Comparison of 2-dimensional, 3-dimensional, and vascular ultrasonographic parameters for endometrial receptivity between 2 consecutive stimulated in vitro fertilization cycles.

OBJECTIVE: We compared the ultrasonographic parameters for endometrial receptivity between 2 consecutive in vitro fertilization (IVF) cycles in the same patients. METHODS: Patients who had undergone 2 in vitro fertilization cycles between November 2002 and December 2004 were recruited. A 3-dimensional ultrasonographic examination with power Doppler imaging was performed on the day of oocyte retrieval to determine the endometrial thickness, endometrial pattern, pulsatility and resistive indices of uterine vessels, endometrial volume, vascularization index, flow index, and vascularization flow index of endometrial and subendometrial regions. RESULTS: Of 662 patients, 95 (14.4%) underwent 2 consecutive cycles using the same stimulation regimen during the study period. There were no significant differences in these ultrasonographic parameters between the first and second cycles. The intraclass correlation coefficient (ICC) for endometrial volume was significantly higher than that of other ultrasonographic parameters. The ICC for the endometrial thickness, uterine pulsatility index, and endometrial 3-dimensional power Doppler flow indices were similar. CONCLUSIONS: Ultrasonographic parameters for endometrial receptivity were comparable in the 2 consecutive stimulated cycles. The endometrial volume had the highest ICC among these ultrasonographic parameters and was most reproducible between 2 cycles.

A randomized comparison of side effects and patient convenience between Cyclogest suppositories and Endometrin tablets used for luteal phase support in IVF treatment.

OBJECTIVE: This study compared side effects and patient convenience of vaginal progesterone suppositories (Cyclogest) and vaginal progesterone tablets (Endometrin) used for luteal phase support in in vitro fertilization/embryo transfer (IVF/ET) cycles using pituitary downregulation. STUDY DESIGN: One hundred and thirty-two infertile patients were randomized on the day of ET by a computer-generated randomization list in sealed envelopes to receive either Cyclogest 400mg or Endometrin 100mg twice daily for 14 days. On days 6 and 16 after ET, they rated side effects and patient convenience into four grades: none, mild, moderate and severe by completing a questionnaire. RESULTS: No significant differences in perineal irritation were found on days 6 and 16 after ET between the two groups, although there was a trend of fewer patients with perineal irritation in the Endometrin group. Significantly more patients in the Endometrin group had difficulty of administration on day 6 after ET. There were no differences in the hormonal profile on day 6 after ET and IVF outcomes between the two groups. CONCLUSION: There was no difference in perineal irritation after the use of Cyclogest suppositories or Endometrin tablets for luteal phase support although more patients found administration of Endometrin tablets difficult.

Endometrial and subendometrial vascularity is higher in pregnant patients with livebirth following ART than in those who suffer a miscarriage.

BACKGROUND: Blood flow towards the peri-implantation endometrium may have effects on miscarriage and live birth following assisted reproduction treatment, in addition to its role in implantation. METHODS: Three-dimensional ultrasound examination with power Doppler was performed on the day of oocyte retrieval in stimulated IVF cycles and on LH + 1 day in frozen thawed-embryo transfer (FET) cycles to measure endometrial thickness, endometrial pattern, uterine artery Doppler flow indices, endometrial volume, vascularization index (VI), flow index (FI), vascularization flow index (VFI) of endometrial and subendometrial regions. RESULTS: In stimulated IVF cycles, 45 (28.0%) out of 161 pregnant patients subsequently miscarried. Patients in the live birth group had significantly higher endometrial VI and VFI and subendometrial VI, FI and VFI, when compared with those in the miscarriage group. In a multiple logistic regression analysis, only endometrial VI was significantly associated with the chance of live birth with an odds ratio of 1.384 [95% confidence interval (CI) 1.025-1.869, P = 0.034]. For FET cycles, patients in the live birth group had significantly higher endometrial VFI, subendometrial VI and VFI than those in the miscarriage group. CONCLUSIONS: Endometrial and subendometrial vascularity was significantly higher in pregnant patients with live birth following stimulated IVF and FET treatment than in those who suffered a miscarriage.

Clinical applications of mifepristone.

Mifepristone is a progesterone antagonist that has been studied for a number of clinical applications. It is a well-known abortifacient that is effective for both first- and second-trimester medical abortion when used with a prostaglandin analog. It is also an effective cervical priming agent that can be used to soften the cervix before surgical evacuation. Its clinical efficacy as an emergency contraception has been proven. Other applications including treatment for fibroids, endometriosis and various cancers have been explored. However, its association with abortion limits the applications of mifepristone in many of these areas.

The use of misoprostol for early pregnancy failure.

PURPOSE OF REVIEW: This paper reviews the current management of early pregnancy failure with particular emphasis on the use of misoprostol. RECENT FINDINGS: Medical management using misoprostol is effective for the management of miscarriages. The success rate ranged from 84 to 93% depending on the regimen of misoprostol, the duration of waiting period and the types of miscarriage. SUMMARY: Miscarriages occur in 10 to 20% of all pregnancies. Surgical evacuation has been used to empty the uterus. Recently, medical treatment using misoprostol has been studied for the management of miscarriage. It avoids surgery and its associated complications. Compared to expectant management, the success rate is higher. Nonsurgical management takes a longer period to reach the endpoint and medical management is associated with side effect of medication. Studies have shown that medical management is safe and acceptable to women. The optimal regimen of medical management, however, is yet to be determined.

The prevalence of polycystic ovaries in Chinese women with a history of gestational diabetes mellitus.

In the present study we aimed to define the prevalence of polycystic ovaries (PCO), using the revised ultrasound criterion, in Chinese women with previous gestational diabetes mellitus (GDM), as well as their associated clinical, hormonal and biochemical characteristics. Seventy Chinese women with previous GDM were recruited as the study group. The control group comprised women matched for age, parity and delivery year who had a normal oral glucose tolerance test during their index pregnancy. Two- and three-dimensional ultrasound scans were performed to study ovarian morphology and ovarian stromal blood flow. Anthropometric, hormonal and biochemical profiles were compared between women with and without ultrasound features of PCO. The prevalence of PCO in Chinese women was 23%. The group with a history of GDM had a higher but not statistically significant prevalence of PCO (34%). Compared with controls, they had significantly higher incidence of obesity, impaired glucose tolerance or diabetes, fasting insulin and leptin levels, and their lipid profile was less favorable. Also, their level of sex hormone-binding globulin was significantly lower and hence their free androgen index was higher, and so was their level of dehydroepiandrosterone sulfate. There was a trend for the study group to have higher ovarian stromal blood flow.

The pharmacokinetics and different regimens of misoprostol in early first-trimester medical abortion.

Misoprostol is a synthetic prostaglandin E(1) analogue that is commonly used for medical abortion. It can be given orally, vaginally and sublingually. A pharmacokinetic study has shown that sublingual misoprostol has the shortest onset of action, the highest peak concentration and the greatest bioavailability among the three routes of administration. Earlier clinical trials have shown that vaginal misoprostol is superior to oral misoprostol when combined with mifepristone for early first-trimester medical abortion. Recent studies on the clinical efficacy of sublingual misoprostol have demonstrated that it is as effective as vaginal misoprostol. Further studies are required to determine the optimal dose and route of administration of misoprostol that can give the highest complete abortion rate, lowest ongoing pregnancy rate and least side effects.

Comparison of endometrial and subendometrial blood flows among patients with and without hydrosalpinx shown on scanning during in vitro fertilization treatment.

OBJECTIVE: To compare endometrial and subendometrial blood flows among patients with and without hydrosalpinx (HSP) during in vitro fertilization treatment as measured by a three-dimensional power Doppler ultrasound. DESIGN: A prospective observational study. SETTING: A tertiary assisted-reproduction unit. PATIENT(S): Twenty-one patients with HSP were compared with 42 matched controls without HSP. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Endometrial thickness, endometrial pattern, endometrial volume, pulsatility index (PI) and resistance index (RI) of uterine vessels, and the vascularization index (VI), flow index (FI), and vascularization flow index (VFI) of endometrial and subendometrial regions were measured on the day of oocyte retrieval. RESULT(S): The proportion of the non-multilayered endometrial pattern was significantly higher in the HSP group than in the non-HSP group. Patients in the HSP group had significantly lower endometrial and subendometrial VI and VFI. Endometrial thickness, endometrial volume, uterine PI, uterine RI, and endometrial and subendometrial FI were similar between the two groups. No significant differences were observed in endometrial and subendometrial VI, FI, and VFI among patients with unilateral and bilateral HSP. CONCLUSION(S): A change in endometrial pattern and a decrease in endometrial and subendometrial blood flows may be the reasons for impaired implantation in patients with HSP.

Endometrial, subendometrial, and ovarian stromal blood flow in patients treated with two different doses of recombinant human chorionic gonadotropin.

The effects of two different doses of recombinant hCG on blood flow to the uterus and ovary on the day of oocyte retrieval were studied by three-dimensional Doppler ultrasonography in 60 women during IVF treatment. There were no differences in all the indices of endometrial, subendometrial, and ovarian stromal blood flow in women who had received 250 microg or 500 microg of recombinant hCG for final oocyte maturation.

Ovarian stromal vascularity is not predictive of ovarian response and pregnancy.

The role of ovarian stromal vascularity in the prediction of the ovarian response and pregnancy in infertile women was evaluated by comparing age of women, body mass index (BMI), basal FSH concentration, antral follicle count (AFC) and ovarian stromal vascularity indices measured by three-dimensional power Doppler ultrasound. A total of 111 women in their first IVF cycle were analysed. They were aged <40 years with basal FSH concentration <10 IU/l on recruitment for IVF treatment. AFC, mean ovarian volume and mean ovarian 3D power Doppler flow indices were determined on day 2 of the treatment cycle prior to a standard regimen of ovarian stimulation. Ovarian response was represented by the number of oocytes, serum oestradiol, the duration and dosage of gonadotrophins. AFC achieved the best predictive value in relation to the number of oocytes obtained, followed by age of women and BMI. Basal FSH concentration was the only predictive factor for the duration and dosage of gonadotrophin used. Mean ovarian 3D power Doppler flow indices were not predictive of pregnancy in a multiple logistic regression analysis. Ovarian 3D power Doppler flow indices measured after pituitary down-regulation were not predictive of the ovarian response and pregnancy in the IVF treatment.

The role of endometrial and subendometrial vascularity measured by three-dimensional power Doppler ultrasound in the prediction of pregnancy during frozen-thawed embryo transfer cycles.

BACKGROUND: A good blood supply to the endometrium is usually considered as an essential requirement for implantation. OBJECTIVE: The aim of this study was to evaluate the role of endometrial and subendometrial vascularity in the prediction of pregnancy during frozen-thawed embryo transfer (FET) cycles. METHODS: Women undergoing FET in natural or clomiphene-induced cycles after the first stimulated IVF treatment were recruited. A three-dimensional (3D) ultrasound examination with power Doppler was performed 1 day after the LH surge to determine endometrial thickness, endometrial pattern, pulsatility index (PI) and resistance index (RI) of uterine vessels, endometrial volume, vascularization index, flow index and vascularization flow index of endometrial and subendometrial regions. RESULTS: Women in the pregnant group were significantly younger and used less gonadotrophins in their stimulated cycle. Endometrial thickness, endometrial volume, endometrial pattern, uterine PI, uterine RI, endometrial and subendometrial 3D power Doppler flow indices were similar between the nonpregnant and the pregnant groups. The age of women was the only predictive factor for pregnancy. Receiver operating characteristic curve analysis revealed that the area under the curve was around 0.5 for all ultrasound parameters for endometrial receptivity. CONCLUSION: Vascularity of endometrial and subendometrial layers measured by 3D power Doppler ultrasound is not a good predictor of pregnancy in FET cycles if measured at one time point only.

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 anthropometric 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.

A randomized trial to compare the use of sublingual misoprostol with or without an additional 1 week course for the management of first trimester silent miscarriage.

BACKGROUND: This randomized controlled trial compared the use of sublingual misoprostol with or without an additional 1 week course of sublingual misoprostol for the medical management of silent miscarriage. METHODS: A total of 180 women who had silent miscarriage (<13 weeks) was given 600 microg of misoprostol every 3 h for a maximum of three doses. These women were randomized into two groups: (i) no extended course of misoprostol or (ii) an extended course of sublingual misoprostol 400 microg daily for 1 week. The primary outcome measure was complete miscarriage rate. RESULTS: The success rates for complete miscarriage were similar in both groups (group 1: 92.2%; 95% CI: 86.1-97.5% and group 2: 93.2%; 95% CI: 84.6-96.8%). There were no serious complications. The incidence of diarrhoea was higher (P < 0.01) in the group with an extended course of sublingual misoprostol. Other side-effects were similar. CONCLUSION: Sublingual misoprostol is useful for the management of silent miscarriage. An additional 1 week course of sublingual misoprostol did not improve the success rate or shorten the duration of vaginal bleeding. Instead, it increased the incidence of diarrhoea.

Factors affecting endometrial and subendometrial blood flow measured by three-dimensional power Doppler ultrasound during IVF treatment.

BACKGROUND: No information exists in the literature regarding the factors affecting the blood flow towards the endometrial and subendometrial regions during IVF treatment. METHODS: We examined the effect of women's age, their smoking habits, their type of infertility (i.e. primary or secondary) and parity, causes of infertility and serum estradiol (E2) concentration on endometrial and subendometrial blood flows as measured by a three-dimensional (3D) power Doppler ultrasound during IVF treatment. All patients received a standard long protocol of ovarian stimulation and serum E2 concentration was determined on the day of hCG. 3D ultrasound examination with power Doppler was performed on the day of oocyte collection to determine vascularization index (VI), flow index (FI) and vascularization flow index (VFI) of endometrial and subendometrial regions. RESULTS: The age of women, their smoking habits, their types of infertility and parity and causes of infertility had no effect on the endometrial and subendometrial 3D power Doppler flow indices. There was a negative correlation between serum E(2) concentration and endometrial FI (r = -0.109; P = 0.006). CONCLUSIONS: Endometrial blood flow in IVF treatment was negatively affected by serum E2 concentration only.