Received Clomiphene Citrate Research Articles

Ovulation triggers in anovulatory women undergoing ovulation induction.

Anovulation is a common cause of infertility. Drugs used to treat anovulation include selective oestrogen receptor modulators, aromatase inhibitors and gonadotrophins. Ovulation triggers are used with these drugs, as a surrogate for the hormonal surge seen in spontaneous menstrual cycles, to control the timing of ovulation and the timing of sexual intercourse. Ovulation triggers given without reliable evidence of oocyte maturity could be inappropriately timed; they increase costs, and the need to time intercourse precisely after the ovulation trigger is given adds to psychological stress.This is an update of a Cochrane review first published in Issue 3, 2008, of the Cochrane Database of Systematic Reviews. To determine the benefits and harms of administering an ovulation trigger to anovulatory women receiving treatment with ovulation-inducing agents in comparison with spontaneous ovulation following ovulation induction. We updated searches of the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and PsycINFO to November 2013. We checked conference proceedings, trial registries and reference lists and contacted researchers. Parallel-group, randomised, controlled trials (RCTs) evaluating the administration of an ovulation trigger to anovulatory women receiving treatment with ovulation-inducing agents. We independently assessed trial eligibility and trial quality and extracted data. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous data and used the random-effects model in meta-analyses when significant heterogeneity was present. We assessed overall quality of the evidence by using the GRADE approach. No new trials were identified. This review includes two RCTs with low risk of bias that compared urinary human chorionic gonadotrophin (hCG) versus no treatment in anovulatory women receiving clomiphene citrate. Urinary hCG did not result in an increase in live birth rate over no hCG (OR 0.97, 95% CI 0.52 to 1.83; two trials, 305 participants, I(2) = 16%; low-quality evidence), but very serious imprecision around the effect estimate reduces our confidence in the apparent lack of effect of hCG as an ovulation trigger in clomiphene-induced cycles in anovulatory women.Among this review's secondary outcomes, urinary hCG may not increase ovulation rate (OR 0.99, 95% CI 0.36 to 2.77; two trials, 305 participants, I(2) = 55%; low-quality evidence), clinical pregnancy rate (OR 1.02, 95% CI 0.56 to 1.89; two trials, 305 participants, I(2) = 35%; low-quality evidence) or miscarriage rate in pregnant women (OR 1.19, 95% CI 0.17 to 8.23; two trials, 54 participants, I(2) = 0%; low-quality evidence). Multiple pregnancies and preterm deliveries were uncommon, and ovarian hyperstimulation syndrome, adverse events and deaths were not reported as outcomes in either trial. We found no trials evaluating other ovulation triggers. Evidence is inadequate to recommend or refute the use of urinary hCG as an ovulation trigger in anovulatory women treated with clomiphene citrate. We found no trials evaluating the use of ovulation triggers in anovulatory women treated with other ovulation-inducing agents.

A randomized trial comparing the ovulation induction efficacy of clomiphene citrate and letrozole.

Background:Letrazole is an aromatase inhibitor, which is useful in ovulation induction. However, evidence on its efficacy over clomiphene citrate, which is the first of drug used for therapy of anovulation, is insufficient in Indian patients.Aims:To compare the efficacy of letrozole and clomiphene citrate in attaining optimal follicular growth.Materials and Methods:The study was conducted in the infertility clinic of Mahatma Gandhi Medical College and Research Institute, Pondicherry, India from June 2008 to December 2009. Fifty women with ovulatory dysfunction as a cause of infertility were enrolled and randomized into two groups of 25 each. Group 1 received clomiphene citrate in incremental dose from 50 mg up to150 mg and Group 2 patient received letrozole in incremental dose from 2.5 mg to 7.5 mg, depending upon the ovulation response. In both the groups, number of follicles, diameter of large follicle, endometrial thickness, and serum estradiol and pregnancy rate were compared. The data from both groups are represented as mean and standard deviation and statistically compared using Student's t test.Results:The number of follicles (1.89 ± 0.9 vs 1.18 ± 0.393) and serum estradiol levels (437.5 ± 293.7 pg/mL vs 291.82 ± 59.86 pg/mL) were higher in Group 1, while follicular diameter (20.67 ± 0.970 mm vs. 20.76 ± 0.903 mm) and endometrial thickness (8.5 mm vs.7.4 mm) were similar in both the Groups.Conclusions:Although letrozole is used for ovulation induction in anovulatory infertility, no significant beneficial effects of letrozole compared to use of clomiphene citratewere observedin ourstudy. Hence, we concur with the use of clomiphene citrate as the first line of drug for ovulation induction in Indian population and warrant larger size studiesto further validate our results.

Assessment of endometrial receptivity using Doppler ultrasonography in infertile women undergoing intrauterine insemination

Objective: The aim of this study was assessment of subendometrial blood flow with Doppler ultrasonography as an indicator of endometrial receptivity in stimulated cycles for intrauterine insemination (IUI).Patients and methods: This prospective study enrolled 90 women scheduled for IUI after ovarian stimulation randomly assigned to one of the three equal groups; group (C) received Clomiphene citrate, group (H) received HMG and group (CH) received Clomiphene citrate in addition to HMG. All participants had ultrasound folliculometry starting on day 9, followed by transvaginal Doppler study of the subendometrial blood flow and perifollicular blood flow on the day of detecting at least one follicle >18 mm. Resistivity index (RI) and pulsatility index (PI) of subendometrial and perifollicular flow were measured. Endometrial thickness was measured on day of hCG injection.Results: Group (H) showed significantly higher frequency of subendometrial flow (80%) compared to the other two groups (p = 0.009). In cases of positive subendometrial flow, the RI and PI were significantly lower in group (H) compared to the other two groups (p = 0.007 and 0.012, respectively). Endometrial thickness was significantly lower in group (C) compared to group (H) (p < 0.001) and group (CH) (p < 0.001). Successful intrauterine implantation was documented in a total of 16 women (17.8%); the highest frequency was in group (H) (23.3%) and the lowest in group (C), however, the difference between the three groups was not significant (p = 0.372). Subendometrial indices and perifollicular RI were significantly lower in cases of successful implantation, while endometrium was significantly thicker in these cases (p < 0.001).Conclusion: The presence of subendometrial flow is associated with successful IUI in women under stimulated cycles undergoing IUI. HMG seems a superior option for induction of ovulation regarding success of implantation.

The Predictive Value of Circulating Anti-Müllerian Hormone in Women With Polycystic Ovarian Syndrome Receiving Clomiphene Citrate: A Prospective Observational Study

Elevated serum anti-Müllerian hormone (AMH) concentration in women with polycystic ovarian syndrome (PCOS) is known to lower sensitivity of ovarian follicles to circulating FSH. This effect may compromise the outcome of clomiphene citrate (CC) ovulation induction. The objective of the study was to investigate the impact of high circulating AMH on the outcome of CC ovulation induction in women with PCOS. This was a prospective cohort observational study. The study was conducted at the Fertility Unit, Derby, United Kingdom. Sixty anovulatory women with PCOS participated in the study. Serum AMH concentrations were measured on cycle day 2 during 187 CC cycles. These concentrations were compared between responders and nonresponders. The receiver-operating characteristic curve was used to evaluate the prognostic value of circulating AMH. The success rates of CC were compared between patients with high vs low AMH levels. The dose of CC required to achieve ovulation was correlated with serum AMH concentrations. Ovulation and pregnancy rates were measured. Serum AMH concentrations were significantly (P < .001) lower in responders (achieving ovulation) vs nonresponders (mean ± SEM, 2.5 ± 0.1 vs 5.8 ± 0.7 ng/mL, respectively). Similarly, serum AMH concentrations were significantly (P = .046) lower in pregnant (3.0 ± 0.4 ng/mL) vs nonpregnant patients (4.4 ± 0.5 ng/mL). There was a significant (P = .02) gradient increase of serum AMH levels with the increasing dose of CC required to achieve ovulation. The receiver-operating characteristic curve showed AMH to be a useful predictor of no ovulation (area under the curve, 0.809; P < .001) with a useful cutoff level of 3.4 ng/mL. Ovulation and pregnancy rates were significantly higher (97%, P < .001, and 46%, P = .034) in patients with low AMH (<3.4 ng/mL) vs women with AMH 3.4 ng/mL or greater (48% and 19%). PCOS women with high circulating AMH (≥ 3.4 ng/mL) seem to be resistant to CC and may require a higher starting dose.

Progesterone luteal support after ovulation induction and intrauterine insemination: a systematic review and meta-analysis

To evaluate the effect of luteal phase P support after ovulation induction IUI. A systematic review and meta-analysis. Not applicable. Undergoing ovulation induction IUI. Any form of exogenous P in ovulation induction IUI cycles. Clinical pregnancy and live birth. Five trials were identified that met inclusion criteria and comprised 1,298 patients undergoing 1,938 cycles. Clinical pregnancy (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.15-1.98) and live birth (OR 2.11, 95% CI 1.21-3.67) were more likely in P-supplemented patients. These findings persisted in analyses evaluating per IUI cycle, per patient, and first cycle only data. In subgroup analysis, patients receiving gonadotropins for ovulation induction had the most increase in clinical pregnancy with P support (OR 1.77, 95% CI 1.20-2.6). Conversely, patients receiving clomiphene citrate (CC) for ovulation induction showed no difference in clinical pregnancy with P support (OR 0.89, 95% CI 0.47-1.67). Progesterone luteal phase support may be of benefit to patients undergoing ovulation induction with gonadotropins in IUI cycles. Progesterone support did not benefit patients undergoing ovulation induction with CC, suggesting a potential difference in endogenous luteal phase function depending on the method of ovulation induction.

FERTILITY ACTIVITY OF AQUEOUS LEAF EXTRACT OF TAPINANTHUS BANGWENSIS ON OVULATION IN FEMALE‐SPRAGUE DAWLEY RATS

The fertility activity of Tapinanthus bangwensis in female rats were investigated in the present study. Twenty four cyclic female rats were administered orally at 1g/kg body weight between 140 and 200g. This was confirmed by checking their vaginal smear for four consecutive cycles.The animals were divided into eight groups of three rats each, group 1 animals served as the control and received equivalent volume of distilled water. Group 2 animals received clomiphene citrate( a fertility enhancing drug), group 3 received duofem(a contraceptive drug), Group 4,5 and 6 received the aqueous leaf extract at 100mg/kg, 200mg/kg and 300mg/kg respectively. group 7 received Vit E and group 8 received Folic acid. They were all administered orally at 9:00am on proestrus to determine it's effect on ovulation. Results revealed a significant difference at P&lt;0.05 between the groups that received the extract at 100mg/kg, 200mg/kg and 300mg/kg. when compared to the control groups. The extract group gave higher mean values of 13.1 as compared to the control of mean value 7.3. Our result gives added scientific support to the use of Tapinanthus bangwensis in the treatment of infertility related problems in women.

RETRACTED: Role of phyto-oestrogens in ovulation induction in women with polycystic ovarian syndrome

To study the role of a phyto-oestrogen, Cimicifuga racimosa extract (Klimadynon(®), Bionorica, Neumarkt i.d.OBf., Germany), in ovulation induction in women with polycystic ovarian syndrome (PCOS). Prospective randomized controlled trial in Minia University Hospital, Minia, Egypt. One hundred women with PCOS were allocated into one of two groups: one group (n=50) received clomiphene citrate 100mg daily for 5 days, and the other group (n=50) received C. racimosa 20mg daily for 10 days. Both groups received medication starting from the second day of the cycle for three consecutive cycles, during which changes in follicle-stimulating hormone (FSH), luteinizing hormone (LH), FSH/LH ratio, progesterone, endometrial thickness and pregnancy rate were measured. The groups were similar in terms of age, clinical presentation and hormonal levels before treatment. Following treatment, significant favourable changes in LH level and FSH/LH ratio (p=0.007 and 0.06, respectively) were seen in the Klimadynon group. In this group the progesterone level was higher from the first treatment cycle, indicating better ovulation (p=0.0001), and endometrial thickness was greater (p=0.0004). The pregnancy rate was higher in the Klimadynon group but the difference between the groups was not significant (p=0.1). Phyto-oestrogen can be used as an alternative to clomiphene citrate for ovulation induction in women with polycystic ovarian syndrome.

Asthma in children born after infertility treatment: findings from the UK Millennium Cohort Study

STUDY QUESTIONIs asthma more common in children born after subfertility and assisted reproduction technologies (ART)?SUMMARY ANSWERYes. Asthma, wheezing in the last year and anti-asthmatic medication were all more common in children born after a prolonged time to conception (TTC). This was driven specifically by an increase in children born after ART.WHAT IS KNOWN ALREADYFew studies have investigated any association between ART and asthma in subsequent children, and findings to date have been mixed. A large registry-based study found an increase in asthma medication in ART children but suggests underlying infertility is the putative risk factor. Little is known about asthma in children after unplanned or mistimed conceptions.STUDY DESIGN, SIZE, DURATIONThe Millennium Cohort Study is a UK-wide, prospective study of 18 818 children recruited at 9 months of age. Follow-up is ongoing. This study analyses data from follow-up surveys at 5 and 7 years of age (response rates of 79 and 70%, respectively).PARTICIPANTS/MATERIALS, SETTING, METHODSSingleton children whose natural mothers provided follow-up data were included. Mothers reported whether their pregnancy was planned; planners provided TTC and details of any ART. The population was divided into ‘unplanned’ (unplanned and unhappy), ‘mistimed’ (unplanned but happy), ‘planned’ (planned, TTC < 12 months), ‘untreated subfertile’ (planned, TTC >12 months), ‘ovulation induced’ (received clomiphene citrate) and ‘ART’ (IVF or ICSI). The primary analysis used the planned children as the comparison group; secondary analysis compared the treatment groups to the children born to untreated subfertile parents. Outcomes were parent report of asthma and wheezing at 5 and 7 years, derived from validated questions in the International Study of Asthma and Allergies in Childhood, plus use of anti-asthmatic medications. A total of 13 041 (72%) children with full data on asthma and confounders were included at 5 years of age, and 11 585 (64%) at 7 years.MAIN RESULTS AND THE ROLE OF CHANCECompared with planned children, those born to subfertile parents were significantly more likely to experience asthma, wheezing and to be taking anti-asthmatics at 5 years of age [adjusted odds ratio (OR): 1.39 (95% confidence interval (CI): 1.07, 1.80), OR: 1.27 (1.00, 1.63) and OR: 1.90 (1.32,2.74), respectively]. This association was mainly related to an increase among children born after ART (adjusted OR: 2.65 (1.48, 4.76), OR: 1.97, (1.10, 3.53) and OR: 4.67 (2.20, 9.94) for asthma, wheezing and taking anti-asthmatics, respectively). The association was also present, though reduced, at the age of 7 years.LIMITATIONS, REASONS FOR CAUTIONThe number of singletons born after ART was relatively small (n = 104), and as such the findings should be interpreted with caution. However, data on a wide range of possible confounding and mediating factors were available and analysed. The data were weighted for non-response to minimize selection bias.WIDER IMPLICATIONS OF THE FINDINGSThe findings add to the growing body of evidence suggesting an association between subfertility, ART and asthma in children. Further work is needed to establish causality and elucidate the underlying mechanism. These findings are generalizable to singletons only, and further work on multiples is needed.STUDY FUNDING/COMPETING INTEREST(S)This study was funded by a Medical Research Council project grant. No competing interests.

Clomiphene citrate versus high doses of gonadotropins for in vitrofertilisation in women with compromised ovarian reserve: a randomised controlled non-inferiority trial

BackgroundThe aim of the present randomised controlled non-inferiority trial is to test whether in women with compromised ovarian reserve requiring in vitro fertilisation, a protocol of ovarian stimulation using exclusively clomiphene citrate performs similarly to a regimen with high doses of gonadotropins.MethodsWomen with day 3 serum FSH > 12 IU/ml on at least two occasions or previous poor response to hyper-stimulation were recruited at four Italian infertility units. Selected women were allocated to clomiphene citrate 150 mg/day from day 3 to day 7 of the cycle (n=145) or to a short protocol with GnRH agonist 0.1 mg and recombinant FSH 450 IU daily (n=146). They were randomised by means of a computer-generated list into two groups. The study was not blinded. The main outcome of the study was the delivery rate per started cycle.ResultsThe study was interrupted after the scheduled two years of recruitment before reaching the sample size. 148 women were allocated to clomiphene citrate and 156 to the short protocol with high doses of gonadotropins; 124 and 125 participants were analysed in the groups, respectively. Women allocated to high doses of gonadotropins retrieved more oocytes and had a higher probability to perform embryo-transfer. However, the chances of success were similar. The delivery rate per started cycle in women receiving clomiphene citrate and high-dose gonadotropins was 3% (n=5) and 5% (n=7), respectively (p=0.77). The mean estimated cost per delivery in the two groups was 81,294 and 113,107 Euros, respectively. No side-effects or adverse events were observed.ConclusionsIn women with compromised ovarian reserve selected for in vitro fertilisation, ovarian stimulation with clomiphene citrate or high-dose gonadotropins led to similar chances of pregnancy but the former is less expensive.Trial registrationTrial registered on http://www.clinicaltrials.gov (NCT01389713)

Effects of pregnancy planning, fertility, and assisted reproductive treatment on child behavioral problems at 5 and 7 years: evidence from the Millennium Cohort Study

To examine the effects of pregnancy planning, time to conception (TTC), and assisted reproductive technologies (ART) on child behavior. Prospective cohort study. Not applicable. A total of 12,380 singletons recruited at 9 months and followed-up at 5 and 7 years. Conceptions were divided into "unplanned" (unplanned, unhappy), "mistimed" (unplanned, happy), "planned" (planned, TTC <12 months), "subfertile" (planned, TTC ≥ 12 months), "ovulation induced" (received clomiphene citrate), and "ART" (IVF or intracytoplasmic sperm injection). None. Child behavior (Strengths and Difficulties Questionnaire [SDQ]). Mistimed and unplanned children had higher average SDQ scores at age 5 and 7 years and were significantly more likely to have a clinically relevant behavioral problem compared with the planned group. The ART children had significantly higher average SDQ scores at both 5 and 7 years compared with the planned group. An increase in clinically relevant behavioral problems was observed at 5 years (odds ratio 2.05 [95% confidence interval 0.96, 4.42]) but failed to reach statistical significance. No effects were observed in the subfertile and ovulation-induced groups. Unplanned and mistimed children exhibit more behavioral problems than their planned peers. Though ART children have higher mean total difficulties scores, this did not translate into a statistically significant increase in clinically relevant behavioral problems.

RETRACTED ARTICLE: Sequential clomiphene citrate/hMG versus hMG for ovulation induction in clomiphene citrate-resistant women

This study was designed to compare sequential clomiphene citrate/hMG regimen to hMG regimen for ovulation induction in clomiphene citrate-resistant women. A comparative prospective study. Ninety infertile women were randomized to receive either sequential CC/hMG regimen (45 women) or low-dose step-up protocol of hMG (45 women). All participants had received at least six consecutive cycles of clomiphene citrate for ovulation induction within the last year before inclusion in this study, but they did not conceive. The CC/hMG regimen group received clomiphene citrate 100 mg/day for 5 days, followed by hMG 75 IU for 4 days. The hMG group received low-dose step-up protocol for 10-14 days. To detect the number and size of the follicles, TVS was done on cycle day 8 and repeated daily or every other day according to follicular development. When one to three follicles reached a diameter ≥18 mm, hCG injection was scheduled. Before hCG injection, the E2 level and endometrial thickness were evaluated. β-hCG levels were measured on cycle day 22. There was no significant difference between the two studied groups regarding the demographic data, sperm parameters, and day 3 FSH, LH and estradiol. Also, there was no significant difference between the two studied groups regarding endometrial thickness, number of mature follicles, peak of E2 before hCG injection and number of cases that developed ovarian cyst or OHSS. The dose of gonadotropins used was significantly low in the CC/hMG group compared to the hMG group (295.2 ± 75.5 vs. 625.3 ± 65.0, respectively), and the pregnancy rate was significantly high in the CC/hMG group compared to the hMG group [12 (26.7 %) vs. 3 (6.7 %), respectively, p < 0.05]. The sequential CC/hMG regimen is as effective as hMG regimen for ovulation induction, produces satisfactory pregnancy results and reduces the treatment cost.

Comparison of Ovarian volume and Antral follicle count with Endocrine tests for prediction of responsiveness in ovulation induction protocols

Background:The aim of this study was to determine if the basal antral follicle number and ovarian volume contributes to the prediction of responsiveness in ovulation induction protocol and comparison of it with hormonal tests.Materials and Methods:52 irregularly-menstruating patients, aged 18-46 years, participated in this prospective study. All the patients underwent a transvaginal sonography to measure the basal ovarian volume and the basal antral follicles count (AFC). Clomiphene citrate challenge test was measured by summation of measurements of FSH on day 2 and 10. All the women received clomiphene citrate from day 2 to 6. Ovarian responsiveness was measured 1 week after termination of clomiphene citrate and was used as gold standard.Results:Multiple regression analysis revealed that AFC was the only significant factor for ovarian responsiveness prediction. The area under the curve for AFC to discriminate responder ovaries was 0.66 (95% confidence interval, 0.87-0.99). The cutoff value for predicting ovarian responsiveness was 15.5.Conclusion:AFC can contribute to the prediction of responsiveness in ovulation induction protocol better than ovarian volume and hormonal tests.

Are children born after infertility at increased risk of Asthma?

ObjectivesTo examine whether children born after infertility or assisted reproductive treatment (ART) are at increased risk of asthma by age 7.DesignProspective population-based cohort (Sweeps 1, 3 and 4 of the...

Pregnancy outcomes in women with thin endometrium undergoing ovulation induction with clomiphene citrate

Thinning of the endometrium has been observed in women receiving clomiphene citrate (CC) for ovulation induction (OI). Although an endometrial stripe (ES) of <7mm is often considered thin, the minimally acceptable thickness for CC cycles has not been established. The objective is to evaluate the effects of a thin ES on day of HCG (<6mm and 6-7mm) compared to a thick ES (≥7mm) on OI outcomes.

Effect of pregnancy planning and fertility treatment on cognitive outcomes in children at ages 3 and 5: longitudinal cohort study

Objective To investigate how pregnancy planning, time to conception, and infertility treatment influence cognitive development at ages 3 and 5.Design Prospective population based cohort study.Setting Millennium Cohort Study in the...

Comparison of the effect of two different doses of recombinant gonadotropin for ovarian stimulation on the outcome of intrauterine insemination

Objective The aim of this study was to identify an optimal stimulation protocol for intrauterine insemination (IUI) to obtain an acceptable pregnancy rate and low frequency of multiple pregnancies. Materials and Methods In total, 340 patients, who received intrauterine insemination because of ovulation dysfunction, were enrolled in this study. Group I consisted of 203 patients who received recombinant FSH (r-FSH) 150 U every other day as an ovulation induction agent. Group II consisted of 137 patients who received r-FSH 100 U every other day as an ovulation induction agent. All patients in both groups also received clomiphene citrate 100 mg/day for consecutive five days from the fifth day of the cycle. Only patients with at least two follicles >18 mm on the human chorionic gonadotropin injection days were included in this study. Results The clinical pregnancy rate was 14.8% (30/203) in Group I compared with 20.4% (28/137) in Group II, p > 0.05. The incidence of multiple pregnancy was 41.7% (10/24) in Group I compared with 12.5% (3/24) in Group II, p < 0.05. Conclusions The concurrent use of low-dose r-FSH and clomiphene citrate would seem not only to be cost-effective but also highly satisfactory in that it prevents high-order multiple pregnancies.

Letrozole versus Clomiphene Citrate for Induction of Ovulation in Patients with Polycystic Ovarian Syndrome Undergoing Intrauterine Insemination

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting women in the reproductive age group, and is one of the most common causes of hyperandrogenic anovulatory infertility. The aromatase inhibitor, letrozole, has been used for induction of ovulation. The purpose of this study was to compare the effects of letrozole and clomiphene citrate in induction of ovulation among patients with PCOS undergoing intrauterine insemination.MethodsIn a double-blind randomized study, 60 infertile patients with PCOS received standard doses of either clomiphene citrate or letrozole as an induction protocol prior to intrauterine insemination. A hormonal profile, pelvic ultrasound, hysterosalpingogram, and/ or laparoscopy were done for all patients. The patients were monitored for ovulation by translational ultrasonographic folliculometry, with measurement of number and size of the follicles, as well as endometrial thickness. Human chorionic gonadotrophin (HCG) was injected intramuscularly when at least one mature follicle ≥18 mm diameter was detected, and intrauterine insemination was performed 32–36 hours later. Transvaginal ultrasound and β-HCG measurement were performed for confirmation of pregnancy.ResultsLetrozole and clomiphene citrate achieved follicle maturation within a mean ± standard deviation (SD) of 13.2 ± 1.53 and 14.1 ± 1.35 days, respectively, showing no significant difference (P > 0.05). The mean number of follicles reaching ≥18 mm on the day of HCG administration was significantly higher in patients who received clomiphene citrate (2.9 ± 1.77) than in those receiving letrozole (1.2 ± 0.9). Letrozole had a significantly greater effect than clomiphene citrate on endometrial thickness (9.16 ± 1.36 versus 4.46 ± 1.71). The number of pregnancies achieved in the letrozole group was significantly (P < 0.05) greater than in the clomiphene group.ConclusionLetrozole in patients with PCOS is as effective as clomiphene citrate in inducing ovulation, and although the number of follicles produced by induction with letrozole were less than those produced by clomiphene, letrozole had a significantly greater effect on endometrial thickness than clomiphene citrate, and the incidence of pregnancy after intrauterine insemination was significantly higher, with a lower incidence of multiple pregnancy.

061 The effects of pregnancy planning, time to conception and art on expressive language ability at 3 years

ObjectiveTo examine the effects of pregnancy planning, time to conception and assisted reproductive treatment on expressive language ability at 3 years.DesignPopulation-based cohort (Sweeps 1 and 2 of the UK Millennium...

Osteopontin and αvβ3 integrin as markers of endometrial receptivity: the effect of different hormone therapies

The osteopontin: alphavbeta3 integrin complex has been proposed as a means of distinguishing receptive from non-receptive endometrium in clinical practice, thus offering new directions for the development of contraceptive approaches targeted to the endometrium as well as a better understanding of occult causes of infertility in women. Histological dating and immunohistochemical study were performed in control and study cycles in seven groups of women including 10 subjects per group and who received clomiphene citrate, ovarian stimulation for IVF, oral contraception, dehydrogesterone for endometrial luteal phase defect, two different regimens of hormone replacement therapy, or no treatment. Ten healthy fertile women served as a general control group. Osteopontin and alphavbeta3 integrin expression in the human endometrium was closely related to endometrial maturation and this was irrespective of the endometrium being in-phase or out-of-phase and the hormonal treatment (or no treatment) received. In conclusion, immunohistochemical assessment of the endometrium indicates that the use of osteopontin and alphavbeta3 integrin or the osteopontin: alphavbeta3 integrin complex as targets for the development of contraceptive approaches or the understanding of the pathogenesis of female infertility offer little benefit compared with simple histological dating.

A randomized, placebo-controlled study of the influence of instant-release metformin on response to clomiphene citrate and time to conception in polycystic ovary syndrome

OBJECTIVE: To evaluate the influence of instant-release metformin hydrochloride on the response to clomiphene citrate in women with polycystic ovary syndrome who are attempting to conceive. DESIGN: A randomized, triple blind, placebo-controlled design. MATERIALS AND METHODS: Group 1 received clomiphene citrate + placebo(CC + P); group 2 received clomiphene citrate + metformin hydrochloride(CC + M) in 500mg doses three times daily. Clomiphene citrate was progressively increased by 50 mg increments until mid-luteal phase serum progesterone was ≥ 15ng/mL. Participants remained in the study until six ovulatory cycles, as defined by serum progesterone ≥5ng/mL, were completed or conception occurred. Partipants who did not respond to 200mg of CC on cycle days 5-9 were unblinded and those in the placebo group were crossed over to CC + M group. Statistical methods included Wilcoxan tests and survival analyses. RESULTS: 55 women completed at least one treatment cycle for a total of 187 blinded study cycles. In Group 1, 26 women underwent 99 blinded cycles, 20 of whom (76.9%; 95% CI: 58.0%-89.0%) ovulated, and 8 of 26 (30.8%; 95% CI: 16.5%-50%) conceived from blinded cycles. In Group 2, 29 women underwent 88 blinded cycles 17 of whom (58.6%; 95% CI: 40.7%-74.5%) ovulated, and 12 of 29 (41.4%; 95% CI: 25.5-59.3%) conceived from blinded cycles. There were no significant differences in median number of cycles to ovulation or conception. There was a higher chance of conceiving once ovulatory in CC + M (12/17, 70.6%) compared to CC + P (8/20, 40%) (log rank p<0.028), with conception occurring on average 1 month earlier in CC + M (mean 2.4 cycles) compared to CC + P (mean 3.5 cycles). CONCLUSIONS: There were no significant differences in frequency of ovulation or pregnancy rates when metformin was added to clomiphene citrate compared to clomiphene citrate alone. Among ovulatory women there was a shorter time to conception if metformin was administered in combination wtih clomiphene citrate.