Clomiphene Citrate Cycles Research Articles

A higher incidence of smooth endoplasmic reticulum clusters with aromatase inhibitors.

PurposeThis study aimed to analyze whether a regimen of aromatase inhibitor (AI) could reduce the occurrence of smooth endoplasmic reticulum clusters (sERCs) in oocytes.Method(s)The AI and the clomiphene citrate (CC) regimens were compared, regarding the sERC (+) rates and the serum estradiol and progesterone levels on the date of hCG administration, and the duration of AI, CC, and hMG administration.Result(s)The occurrence of sERCs in oocytes from patients treated with AI was significantly higher than that in oocytes from those treated with CC. Both the serum estradiol and progesterone levels were found to be significantly higher in sERC (+) than in sERC (‐) cycles. With regard to the CC cycles, no significant differences were detected. The duration of AI and hMG administration was longer for sERC (+) than for sERC (‐) cycles.ConclusionAs AI did not reduce the occurrence of sERCs, the elevation of estradiol may not be the cause of sERC occurrence but a consequence. Considering the higher levels of progesterone and longer duration of hMG in sERC (+) cycles, the negative effects of premature luteinization, which frequently occur with the AI protocol, should be investigated further.

Sildenafil citrate adjuvant treatment in women with polycystic ovary syndrome following clomiphene failure: A randomized controlled trial

Objective: The widespread classic PCOS treatment algorithm, consisting of 6-12 cycles of clomiphene followed by shifting to gonadotropins in case of failure to conceive, doesn’t really address the cause of failure to conceive despite documented ovulation. Sildenafil citrate improves uterine blood flow, enhances endometrial development and modulates endometrial receptivity. Hence, this study monitored the ovarian response, endometrial development and subendometrial Doppler changes in PCOS women with previous clomiphene citrate failure following the use of adjuvant sildenafil citrate instead of shifting to gonadotropins. Patients and Methods: A double-blinded randomized controlled trial was conducted in Ain-Shams University Women’s Hospital on 850 PCOS women with clomiphene failure. Those were randomized to clomiphene therapy, either with adjuvant placebo or sildenafil citrate (25 mg orally 6 hourly), starting from the 6th day till the end of the cycle.Folliculometry, every other day, started on the 10th day of the cycle. When ≥1 follicle reached a size ≥18mm, transvaginal ultrasound assessment of the endometrium and uterine/subendometrial Doppler was done. The resulting pregnancy rates were recorded. Results: The sildenafil group developed higher endometrial thickness (10.6±1.3 versus 9.4±1.5; p<0.001), a higher percentage of women with trilaminar endometrium (78.35% versus 59.76%; p<0.001) was found while the lower percentage was found with subendometrial and uterine artery Doppler indices (p<0.001 for all). It also developed higher pregnancy rates (43.7% versus 34.5%, p=0.006; NNT=10.8, 95% CI: 6.36 – 37.84).Conclusion: Sildenafil adjuvant therapy significantly increased pregnancy rates, improved endometrial development in terms of endometrial thickness and pattern as well as uterine and subendometrial blood flow.

Luteal-phase progesterone supplementation in non-IVF treatment: a survey of physicians providing infertility treatment

We sought to examine current use of, and indications for, progesterone supplementation in the luteal phase of non-in vitro fertilization (non-IVF) infertility treatments among Obstetrician Gynaecologists (OB/GYN) compared to Reproductive Endocrinology and Infertility (REI) Subspecialists. Using a web-based survey, the practices of U.S. REI and OB/GYN physicians practicing infertility from 2014–2016 were assessed. The main outcome measures were frequency of use and indications for progesterone supplementation for luteal-phase support in non-IVF infertility treatments. Comparisons between physicians groups by indication and treatment type were performed using Chi-square and Fisher’s exact tests. Sixty-four REIs and 49 OB/GYNs completed the survey. One hundred per cent of REI and 73.5% of OB/GYN respondents prescribed progesterone for luteal-phase support as part of non-IVF infertility treatment. The majority of all respondents utilized progesterone supplementation for one or more indications in clomiphene citrate and letrozole treatment cycles. Treatment type was the primary decisional factor reported by REIs (56%) for prescription of luteal-phase progesterone support. Serum progesterone level was reported as the leading decisional factor for luteal-phase supplementation (66.7%) by OB/GYNs. Luteal-phase progesterone supplementation in non-IVF treatments appears common for both physician groups in the United States in spite of lack of evidence supporting its effectiveness.

Gonadotrophins versus clomiphene citrate with or without IUI in women with normogonadotropic anovulation and clomiphene failure: a cost-effectiveness analysis.

Are six cycles of ovulation induction with gonadotrophins more cost-effective than six cycles of ovulation induction with clomiphene citrate (CC) with or without IUI in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC? Both gonadotrophins and IUI are more expensive when compared with CC and intercourse, and gonadotrophins are more effective than CC. In women with normogonadotropic anovulation who ovulate but do not conceive after six cycles with CC, medication is usually switched to gonadotrophins, with or without IUI. The cost-effectiveness of these changes in policy is unknown. We performed an economic evaluation of ovulation induction with gonadotrophins compared with CC with or without IUI in a two-by-two factorial multicentre randomized controlled trial in normogonadotropic anovulatory women not pregnant after six ovulatory cycles with CC. Between December 2008 and December 2015 women were allocated to six cycles with gonadotrophins plus IUI, six cycles with gonadotrophins plus intercourse, six cycles with CC plus IUI or six cycles with CC plus intercourse. The primary outcome was conception leading to a live birth achieved within 8 months of randomization. We performed a cost-effectiveness analysis on direct medical costs. We calculated the direct medical costs of ovulation induction with gonadotrophins versus CC and of IUI versus intercourse in six subsequent cycles. We included costs of medication, cycle monitoring, interventions, and pregnancy leading to live birth. Resource use was collected from the case report forms and unit costs were derived from various sources. We calculated incremental cost-effectiveness ratios (ICER) for gonadotrophins compared to CC and for IUI compared to intercourse. We used non-parametric bootstrap resampling to investigate the effect of uncertainty in our estimates. The analysis was performed according to the intention-to-treat principle. We allocated 666 women in total to gonadotrophins and IUI (n = 166), gonadotrophins and intercourse (n = 165), CC and IUI (n = 163), or CC and intercourse (n = 172). Mean direct medical costs per woman receiving gonadotrophins or CC were €4495 versus €3006 (cost difference of €1475 (95% CI: €1457-€1493)). Live birth rates were 52% in women allocated to gonadotrophins and 41% in those allocated to CC (relative risk (RR) 1.24:95% CI: 1.05-1.46). The ICER was €15 258 (95% CI: €8721 to €63 654) per additional live birth with gonadotrophins. Mean direct medical costs per woman allocated to IUI or intercourse were €4497 versus €3005 (cost difference of €1510 (95% CI: €1492-€1529)). Live birth rates were 49% in women allocated to IUI and 43% in those allocated to intercourse (RR = 1.14:95% CI: 0.97-1.35). The ICER was €24 361 (95% CI: €-11 290 to €85 172) per additional live birth with IUI. We allowed participating hospitals to use their local protocols for ovulation induction and IUI, which may have led to variation in costs, but which increases generalizability. Indirect costs generated by transportation or productivity loss were not included. We did not evaluate letrozole, which is potentially more effective than CC. Gonadotrophins are more effective, but more expensive than CC, therefore, the use of gonadotrophins in women with normogonadotropic anovulation who have not conceived after six ovulatory CC cycles depends on society's willingness to pay for an additional child. In view of the uncertainty around the cost-effectiveness estimate of IUI, these data are not sufficient to make recommendations on the use of IUI in these women. In countries where ovulation induction regimens are reimbursed, policy makers and health care professionals may use our results in their guidelines. This trial was funded by the Netherlands Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). The Eudract number for this trial is 2008-006171-73. The Sponsor's Protocol Code Number is P08-40. CBLA reports unrestricted grant support from Merck and Ferring. BWM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for Merck, ObsEva and Guerbet. NTR1449.

Risk of cancer after assisted reproduction: a review of the available evidences and guidance to fertility counselors.

Infertile women requiring ovarian stimulation and assisted reproduction techniques (ART) are faced with difficult issues. The fear that using hormones could increase their risk of cancer is the most significant. One of the main challenges for assessing cancer risk after ART is the difficulty to separate it from the underlying condition of infertility per se. The delay or the inability to achieve a pregnancy is an important risk factor for breast, endometrial and ovarian cancer. We analyzed the current literature on the topic. The published literature in Medline and Cochrane was screened using the following keywords: ovulation induction, reproductive techniques, clomiphene, in vitro fertilization, fertility agents, female/adverse effects, female/toxicity gonadotropins/ adverse effects or gonadotropins/toxicity and "neoplasms or cancer". A total of 95 articles were evaluated. Limited evidence suggests that high doses or many cycles of clomiphene citrate could increase the risk of endometrial cancer, although the confounding factors of polycystic ovarian disease and overweight are not always considered. In some studies, ART modestly increased the risk of borderline ovarian cancer. Fertility treatments do not increase the risk of breast, cervical, endometrial and ovarian cancers, thyroid, melanoma and colon cancer. Women can be reassured that fertility drugs do not appear to significantly increase the risk of invasive ovarian, endometrial, breast or other cancers, while achieving a pregnancy at an earlier age is a significant protective factor.

Comparison of sonohysterography to hysterosalpingogram for tubal patency assessment in a multicenter fertility treatment trial among women with polycystic ovary syndrome.

To compare saline infusion sonohysterography (SIS) versus hysterosalpingogram (HSG) for confirmation of tubal patency. Secondary analysis of a randomized controlled trial, Pregnancy in Polycystic Ovary Syndrome II (PPCOS II). Seven hundred fifty infertile women (18-40years old) with polycystic ovary syndrome (PCOS) were randomized to up to 5cycles of letrozole or clomiphene citrate. Prior to enrollment, tubal patency was determined by HSG, the presence of free fluid in the pelvis on SIS, laparoscopy, or recent intrauterine pregnancy. Logistic regression was conducted in patients who ovulated with clinical pregnancy as the outcome and HSG or SIS as the key independent variable. Among women who ovulated, 414 (66.9%) had tubal patency confirmed by SIS and 187 (30.2%) had at least one tube patent on HSG. Multivariable analysis indicated that choice of HSG versus SIS did not have a significant relationship on likelihood of clinical pregnancy, after adjustment for treatment arm, BMI, duration of infertility, smoking, and education (OR 1.14, 95% CI 0.77, 1.67, P = 0.52). Ectopic pregnancy occurred more often in women who had tubal patency confirmed by HSG compared to SIS (2.8% versus 0.6%, P = 0.02). In this large cohort of women with PCOS, there was no significant difference in clinical pregnancy rate between women who had tubal patency confirmed by HSG versus SIS. SIS is an acceptable imaging modality for assessment of tubal patency in this population.

Outcomes of random start versus clomiphene citrate and gonadotropin cycles in occult premature ovarian insufficiency patients, refusing oocyte donation: a retrospective cohort study

The aim of this study is to present the clinical outcomes of a random start, a spontaneous folliculogenesis protocol versus Clomiphene Citrate and Gonadotropin treatment in women with occult premature ovarian insufficiency. Women underwent treatment between 1 February 2009, and 30 May 2016. 41 women were treated with the random start protocol while 48 cases received ovarian stimulation with clomiphene and gonadotropins. All included cases met the criteria of 4 months of oligo-ovulation, follicular-stimulating hormone levels over 30 IU/L and anti-Mullerian hormone levels below 0.30 ng/mL. The random start protocol involved following the subjects for up to 6 months until spontaneous folliculogenesis occurred. The mean number of oocytes collected, mature oocytes, fertilized oocytes, and grade II embryos were significantly higher in the random start protocol (p < .05). The doses of gonadotropin administration and hCG were significantly lower in the random start protocol (p < .05). The clinical pregnancy and live birth rates were significantly higher in the random start protocol (p < .05). Likely stimulation is of little benefit in women with occult premature ovarian insufficiency. Observation while waiting for spontaneous folliculogenesis results in better outcomes, and less oocyte collections.

Ovarian stimulation in infertile women treated with the use of intrauterine insemination: a cohort study from China

To study the effectiveness of different ovarian stimulation protocols compared with natural cycle treatment in an intrauterine insemination (IUI) program. Retrospective cohort study. Large reproductive medicine center. Couples with unexplained or mild male-factor infertility. Couples were treated with the use of natural-cycle IUI, or IUI after ovarian stimulation with the use of clomiphene citrate (CC), letrozole, or gonadotropins. Live birth, multiple pregnancy rates, and cumulative live birth rates after three IUI cycles. We performed 14,519 IUI cycles in 8,583 couples. Compared with natural-cycle IUI (6.2%), live birth rates were significantly higher in IUI cycles stimulated with the use of CC (8.9%), letrozole (9.4%) and gonadotropins (9.5%). The multiple pregnancy rate resulting from natural cycles was 0.7%, compared with 4.6% in CC cycles, 1.3% in letrozole cycles, and 4.2% in gonadotropin cycles. Cumulative live birth rates after three IUI cycles were 18.4% after natural-cycle IUI, and 25.7%, 26.2%, and 23.7% with the use of CC, letrozole, and gonadotropins, respectively. In an IUI program for unexplained or mild male-factor infertility, ovarian stimulation with letrozole may significantly increase live birth rates while controlling multiple pregnancy rates.

Ovulation induction in women with polycystic ovarian syndrome: Clomiphene citrate or letrozole?

Objective The objective of this study was to determine first-line infertility therapy in polycystic ovarian syndrome (PCOS) and to compare between clomiphene citrate (CC) and aromatase inhibitors (letrozole) as the standard treatment. Patients and methods This is a prospective randomized study. The study was conducted at El-Galaa Assisted Reproduction Unit, El-Galaa Maternity Teaching Hospital, Cairo, Egypt. Eighty-eight women with PCOS were randomized into two groups. Rotterdam criteria were used to define PCOS: oligomenorrhea less than or equal to 8 menses/year plus either PCOS on ultrasound or clinical/biochemical hyperandrogenism, with the exclusion of other causes. Forty-four patients were randomized to the letrozole group (82 cycles), and the other 44 were randomized to the CC group (78 cycles). The aromatase inhibitor letrozole (5 mg/day) and CC (100 mg/day) were administered orally on days 3–7 of menses. Results Number of follicles, endometrial thickness, estradiol levels on human chorionic gonadotropin day, and pregnancy rates were measured in both groups. The mean age, parity, and duration of infertility in both groups were similar. The number of follicles sized more than 15 mm in diameter was statistically significantly higher in the CC group (3.4 ± 0.4 vs. 2.03 ± 0.2). Ovulation occurred in 68.2% (56/82) of letrozole cycles and 74.3% (58/78) of CC cycles without a statistically significant difference. Median serum estradiol concentrations were significantly higher in the CC group than in the letrozole group (396 ± 84.4 vs. 266.2 ± 55.1 pg/ml). Endometrial thickness by transvaginal ultrasound at the time of human chorionic gonadotropin administration was not statistically significantly different in the two groups (7.8 ± 2.2 and 8.1 ± 1.2 mm in letrozole and CC groups, respectively). The pregnancy rate per cycle was 9.7% in the letrozole group and 7.6% in the CC group without significant statistical difference between the groups. Conclusion Both letrozole and CC have comparable results, with no specific advantage of one over the other for ovulation induction in women with PCOS.

Influence of the conclusion of a recent large cooperative study in changing standard protocol of inducing menses in anovulatory women with oligomenorrhea prior to initiating ovulation induction with anti-estrogens and outcome

To compare pregnancy rates following ovulation induction in anovulatory women with clomiphene citrate vs. letrozole and to determine the relative confounding effect of inducing menses or not. The study also evaluated whether starting these anti-estrogen drugs later in the menstrual cycle has-less adverse effect on endometrial thickness. Prospective series with choice by physician of inducing menses or not or choosing clomiphene citrate or letrozole for ovulation induction. Peak endometrial thickness was compared between drugs and between those conceiving or not. There were 21 first cycles using letrozole and 42 using clomiphene. Menses were not induced in 18/21 (86%) letrozole cycles and 24/42 (57%) clomiphene cycles. Clinical pregnancies occurred in four (22.2%) letrozole cycles without induced menses with one miscarriage vs. 4/24 (16.6%) clomiphene cycles, no mis- carriage. One of three (33.3%) letrozole cycles with menses induced achieved a clinical pregnancy vs. only 1/18 (5.5%) of clomiphene cycles. There were no miscarriages. Though the endometrial thickness was higher with clomiphene without induced menses vs. menses induced (11 mm vs. 9.5 mm), one cannot explain the trend for lower pregnancy rates in women with induced menses because of thinner endometria since the thickness was 10.3 mm for clomiphene and 10.0 with letrozole.

Predictive factors influencing pregnancy rates after intrauterine insemination with frozen donor semen: a prospective cohort study

The extent to which certain parameters can influence pregnancy rates after intrauterine insemination with frozen donor semen was examined prospectively. Between July 2011 and September 2015, 402 women received 1264 IUI cycles with frozen donor semen in a tertiary referral infertility centre. A case report form was used to collect data prospectively. The primary outcome measure was clinical pregnancy rate (CPR), confirmed by detection of a gestational sac and fetal heartbeat using ultrasonography at 7–8 weeks of gestation. Statistical analysis was carried out using generalized estimating equations (GEE) to account for the correlation between observations from the same patient. Overall, CPR per cycle was 17.2%. Multivariate GEE analysis revealed the following parameters as predictive for a successful pregnancy outcome: female age (P = 0.0003), non-smoking or smoking fewer than 15 cigarettes a day (P = 0.0470 and P = 0.0235, respectively), secondary infertility (P = 0.0062), low progesterone levels at day zero of the cycle (P = 0.0164) and use of ovarian stimulation with HMG and recombinant FSH compared with clomiphene citrate and natural cycle (P = 0.0006 and P = 0.0004, respectively). These parameters were the most important factors influencing the success rate in a sperm donation programme.

Endometrial Receptivity Markers in Mice Stimulated With Raloxifene Versus Clomiphene Citrate and Natural Cycles.

Ovulation induction therapy with clomiphene citrate can suppress endometrial receptivity. Raloxifene may be an alternative therapeutic for women with ovulatory disorders. This study aimed to compare the expression of endometrial receptivity markers, including homeobox gene 10 (HOXA10), integrin β3, and leukemia inhibitory factor (LIF), as well as pinopode production during the implantation window in mice stimulated with raloxifene and clomiphene citrate and natural cycles. Thirty-six 8-week-old female Kunming mice were randomly divided into 3 groups (n = 12) and administered daily raloxifene (22 mg/kg), clomiphene citrate (18 mg/kg), and normal saline (1 mL), respectively, by gavage. Two days later, mice were injected with 5 IU human chorionic gonadotropin and mated. Successfully mated female animals were identified with vaginal plugs designated gestation day 1. At day 4.5, pregnant donor mice were euthanized, and uterus samples were collected for immunohistochemistry, quantitative polymerase chain reaction, Western blot, and scanning electron microscopy analyses. Homeobox gene 10, integrin β3, and LIF messenger RNA (mRNA) and protein levels were significantly higher in the raloxifene-treated animals compared with the clomiphene citrate group (all P < .05) but not significantly different from saline group values, except for LIF and integrin β3 mRNA levels (P < .05). Pinopodes were abundant and well developed in the raloxifene and saline groups; however, in the clomiphene citrate-treated mice, fewer and poorly developed pinopodes were obtained. In mice, raloxifene had no effect on HOXA10, integrin β3, and LIF expression as well as pinopode production, suggesting it has no adverse effects on endometrial receptivity. Raloxifene may provide a viable alternative oral ovulation induction agent to clomiphene citrate.

Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS.

In overweight/obese women with polycystic ovary syndrome (PCOS), the relative benefit of delaying infertility treatment to lose weight vs seeking immediate treatment is unknown. We compared the results of two, multicenter, concurrent clinical trials treating infertility in women with PCOS. This was a secondary analysis of two randomized trials conducted at academic health centers studying women 18-40 years of age who were overweight/obese and infertile with PCOS. We compared immediate treatment with clomiphene from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial (N = 187) to delayed treatment with clomiphene after preconception treatment with continuous oral contraceptives, lifestyle modification (Lifestyle: including caloric restriction, antiobesity medication, behavioral modification, and exercise) or the combination of both (combined) from the Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (OWL PCOS) trial (N = 142). Live birth, pregnancy loss, and ovulation were measured. In PPCOS II, after four cycles of clomiphene, the cumulative per-cycle ovulation rate was 44.7% (277/619) and the cumulative live birth rate was 10.2% (19/187), nearly identical to that after oral contraceptive pretreatment in the OWL PCOS trial (ovulation 45% [67/149] and live birth: 8.5% [4/47]). In comparison, deferred clomiphene treatment preceded by lifestyle and combined treatment in OWL PCOS offered a significantly better cumulative ovulation rate compared to immediate treatment with clomiphene. (Lifestyle: 62.0% [80/129]; risk ratio compared to PPCOS II = 1.4; 95% confidence interval [CI], 1.1-1.7; P = .003; combined: 64.3% [83/129]; risk ratio compared to PPCOS II = 1.4; 95% CI, 1.2-1.8; P < .001 and a significantly better live birth rate lifestyle: 25.0% [12/48]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.7; P = .01 and combined: 25.5% [12/47]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.8; P = .01). These data show the benefit of improved ovulation and live birth with delayed infertility treatment with clomiphene citrate when preceded by lifestyle modification with weight loss compared with immediate treatment. Pretreatment with oral contraceptives likely has little effect on the ovulation and live birth rate compared with immediate treatment.

The effect of clomiphene citrate vs. letrozole on post-coital tests

Purpose: To determine if letrozole is less likely to create a hostile cervical mucus than clomiphene citrate. Materials and Methods: ost-coital testing compared at time of peak follicular maturation in women attaining mature follicles in first or second cycle of these wo drugs. The study was randomized. Intercourse occurred at least 8-16 hours before. Results: Poor post-coital tests were found in twice he frequency in letrozole cycles than clomiphene citrate cycles. Conclusions: Despite its shorter half-life, letrozole seems to be as least s likely, if not more, to adversely affect cervical mucus.

A randomized controlled trial evaluating the effect of ethinyl estradiol during clomiphene citrate cycles among women with polycystic ovary syndrome.

To investigate the effects of low-dose ethinyl estradiol (EE) on the clinical pregnancy rate among women with polycystic ovary syndrome (PCOS) undergoing ovulation induction with clomiphene citrate (CC). Between March 12, 2011, and February 10, 2013, a randomized, double-blind, placebo-controlled trial was conducted at the Royan Institute Research Center, Tehran, Iran, among women with PCOS who were aged 25-30 years, were undergoing their first intrauterine insemination cycle, and had a history (≥2 years) of infertility, oligomenorrhea, or amenorrhea. Participants were randomly allocated to receive EE (0.05 mg daily for 5 days) or placebo, co-administered with CC cycles (100 mg daily for 5 days). The primary outcome was clinical pregnancy rate. Analyses were per protocol: patients who discontinued the intervention were excluded. Analyses included 45 women who received CC and EE, and 50 women who received CC and placebo. The number of women who achieved a clinical pregnancy was higher among participants who received CC and EE (13 [29%]) than among those in the control group (5 [10%]; P =0 .02). No adverse effects of EE were reported. The combination of CC and EE seems to increase the clinical pregnancy rate among women with PCOS undergoing intrauterine insemination. ClinicalTrials.gov:NCT01219101.

Redefining and clarifying the relationship between total motile sperm counts (TMSC) and intrauterine insemination (IUI) pregnancy rates

Redefining and clarifying the relationship between total motile sperm counts (TMSC) and intrauterine insemination (IUI) pregnancy rates

Clomid Compared With Follicle-Stimulating Hormone Treatment

INTRODUCTION: Clomiphene citrate and gonadotropins are used during intrauterine insemination cycles to help recruit one or more follicles. The objective of this study is to evaluate whether one treatment confers a higher pregnancy rate over the other, even when number of preovulatory follicles are held constant. METHODS: Data from 1,463 women who underwent 3,960 clomiphene or gonadotropin intrauterine insemination cycles were reviewed. Cycles occurred at Massachusetts General Hospital between 2004 and 2012. Regression models using generalized estimating equations were fit to investigate the relationship between cycle type and clinical pregnancy. Results were adjusted for age, body mass index, infertility diagnosis, day 3 follicle-stimulating hormone, and number of follicles greater than 14 mm. A final model was fit adjusting for endometrial thickness in addition to other covariates. RESULTS: Mean endometrial thickness was 7.0 mm and 8.5 mm among women who underwent clomiphene and gonadotropin cycles, respectively (P<.01). Crude clinical pregnancy rate per intrauterine insemination was 11% and 13% among clomiphene and gonadotropin cycles, respectively. After adjusting for potential confounders including number of follicles, odds of clinical pregnancy was higher among gonadotropin cycles as compared with clomiphene cycles (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1–1.7). When endometrial thickness was also controlled for, odds of clinical pregnancy remained higher among gonadotropin cycles although the strength of the relationship decreased (OR 1.3, 95% CI 1.0–1.6). CONCLUSION: Even when number of follicles is held constant, gonadotropin cycles are more likely to result in clinical pregnancy compared with clomiphene cycles. Differential effects on the endometrium may play a role.

Are uterine and ovarian artery Doppler velocimetry values good pregnancy predictors in clomiphene citrate cycles?

We conducted this prospective study to evaluate the prognostic significance of uterine and ovarian artery Doppler velocimetry in clomiphene citrate (CC) cycles. A total of 80 patients with unexplained infertility were given 100 mg/day of CC from day 3 to day 7 of their cycles in this current prospective study. On cycle day 3, before administration of CC, each patient underwent Doppler transvaginal ultrasonography. The Doppler velocimetries of the right and left uterine and ovarian arteries were recorded and analyzed in association with demographic and clinical parameters. TheThere were 6 out of 80 patients who became pregnant, the overall pregnancy rate in this population was 7.5% for the current study. The cases were divided into two groups according to whether they became pregnant or not. Demographic characteristics showed no statistically significant differences between these groups (p>0.05). However, the duration of infertility did show statistically significant differences between the groups. Doppler velocimetry was not statistically significantly different between the two groups. Doppler velocimetry of the uterine and ovarian arteries is not a factor in the prognosis for pregnancy in CC cycles.

Impact of Male and Female Weight, Smoking, and Intercourse Frequency on Live Birth in Women With Polycystic Ovary Syndrome.

Obese men with normal semen parameters exhibit reduced fertility but few prospective data are available. This study aimed to determine the effect of male factors and body mass among the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) participants. This is a secondary analysis of the PPCOS II trial. A total of 750 infertile women with polycystic ovary syndrome (PCOS) were randomly assigned to up to receive five cycles of letrozole or clomiphene citrate. Females were 18-39-years-old and had a male partner with sperm concentration of at least 14 million/mL who consented to regular intercourse. Analysis was limited to couples with complete male partner information (n = 710). Male body mass index (BMI) was higher in couples who failed to conceive (29.5 kg/m(2) vs 28.2 kg/m(2); P = .039) as well as those who did not achieve a live birth (29.5 kg/m(2) vs 28.1 kg/m(2); P = .047). At least one partner was obese in 548 couples (77.1%). A total of 261 couples were concordant for obesity (36.8%). After adjustment for female BMI, the association of male BMI with live birth was no longer significant (odds ratio [OR] = 0.85; 95 % confidence interval [CI], 0.68-1.05; P = .13). Couples in which both partners smoked had a lower chance of live birth vs nonsmokers (OR = 0.20; 95 % CI, 0.08-0.52; P = .02), whereas there was not a significant effect of female or male smoking alone. Live birth was more likely in couples with at least three sexual intercourse attempts over the previous 4 weeks (reported at baseline) as opposed to couples with lesser frequency (OR = 4.39; 95 % CI, 1.52-12. 4; P < .01). In this large cohort of obese women with PCOS, effect of male obesity was explained by female BMI. Lower chance of success was seen among couples where both partners smoked. Obesity and smoking are common among women with PCOS and their partners and contribute to a decrease in fertility treatment success.

Ovulation rate and cycle characteristics in a subsequent clomiphene citrate cycle after stair-step protocol

To determine the ovulation rate after ovulation induction with clomiphene citrate (CC) in women who had previously been ovulatory after a stair-step (CC-SS) ovulation induction. Retrospective cohort. University-based tertiary fertility center. 61 anovulatory patients <40 years of age with polycystic ovary syndrome who underwent ovulation induction with a CC-SS protocol and a subsequent CC cycle. Ovulation induction with CC. Ovulation rates and cycle characteristics. Of 61 patients who underwent a subsequent CC cycle, 15 (25%) failed to ovulate at the previously ovulatory dose. Of those 15 patients, 13 (86.7%) ovulated after an increase in dose. The total number of follicles ≥15 mm (2.8 ± 1.2 vs. 1.6 ± 0.7) and peak estradiol (E2) levels (604 ± 272 pg/mL vs. 447 ± 218 pg/mL) were statistically significantly higher in the CC-SS cycle compared with the subsequent CC cycle, respectively. The endometrial lining was statistically significantly thinner in the CC-SS than the CC cycle (7.8 ± 1.8 vs. 9.2 ± 2.7, respectively). The majority of patients who ovulate after a CC-SS protocol will ovulate after taking the previously ovulatory CC dose in a subsequent cycle. Those who do not ovulate will likely ovulate with a further increase in CC dose.