Tumors of the central nervous system among women treated with fertility drugs: a population-based cohort study.

PURPOSE: To investigate the association between fertility drugs and tumors of the central nervous system (CNS). METHODS: This cohort study was based on The Danish Infertility Cohort and included 148,016 infertile women living in Denmark (1995-2017). The study cohort was linked to national registers to obtain information on use of specific fertility drugs, cancer diagnoses, covariates, emigration, and vital status. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all CNS tumors and separately for gliomas, meningiomas and diverse benign tumors of the brain and other parts of the CNS. RESULTS: During a median 11.3 years of follow-up, 328 women were diagnosed with CNS tumors. No marked associations were observed between use of the fertility drugs clomiphene citrate, gonadotropins, gonadotropin-releasing hormone receptor modulators and progesterone and CNS tumors. However, use of human chorionic gonadotropin was associated with a decreased rate of meningiomas (HR 0.49 95% CI 0.28-0.87). No clear associations with CNS tumors were observed according to time since first use or cumulative dose for any of the fertility drugs. CONCLUSION: No associations between use of most types of fertility drugs and CNS tumors were observed. However, our findings only apply to premenopausal women and additional studies with longer follow-up time are necessary.

Use of fertility drugs in early-onset female cancer survivors-A Finnish register-based study on 8,929 survivors.

Advances in multimodality cancer treatments have increased the risk of long-term complications in early-onset cancer survivors. For female cancer survivors, these include diminished reproductive function, often resulting in a narrowed fertile window. The aim of our study was to evaluate the use of fertility treatments in cancer survivors (aged 0-39 years at diagnosis) compared to siblings. Data from Finnish registers on cancer, birth and prescribed medications were merged to identify 8,929 survivors and 9,495 siblings without previous deliveries. Fertility drug purchases from 1993 to 2012 at the age of 16-41 years were included. A Poisson regression model was used to estimate incidence rate ratios (IRRs) for the use of fertility drugs, adjusting for age and calendar time at fertility drug purchase. Fertility treatments were more common in survivors compared to siblings, as 6.1% of survivors compared to 3.8% of siblings had bought fertility drugs (IRR 1.43, 95% confidence interval [CI] 1.25-1.65). A subclassification of fertility treatments into ovulation inductions and assisted reproductive technology (ART), showed increased use of ART (IRR 2.41, 95% CI 1.97-2.96), whereas the use of ovulation induction was similar in survivors and siblings. Analyses by calendar time periods showed the use of ART to be significantly higher in the most recent decade, from 2003 onwards. We conclude that cancer survivors have an increased risk for subfertility, which is why fertility counseling is important. However, our results mirror a more active approach among clinicians towards fertility treatments in cancer survivors during the most recent years.

Endocrine approach in the treatment of obesity: Is there any space for the adiponectin action?

Adiponectin is a hormone secreted by adipose tissue, exerting many positive effects in the human body. Its action has been widely studied, placing it into the metabolic health beneficial products of the adipose tissue. Nevertheless, adiponectin has been shown to exert some extra beneficial non metabolic actions, as well. Adiponectin levels can be related to reduced incidence of cancer in obese patients. Moreover, adiponectin has been shown to be implicated in the positive fertility outcomes of women. Some new studies have also indicated that adiponectin has a potential effect in the control of appetite, which raises a question, whether adiponectin could be accredited to be useful in the endocrine evaluation of obesity. Could these additional non-metabolic actions prove its helpfulness?

Mini review: The FDA-approved prescription drugs that induce ovulation in women with ovulatory problems.

Infertility is defined as not being able to become pregnant after 12 months or more of unprotected sexual intercourse. Female infertility as a serious health issue can result from ovulation disorders, menstrual cycle problems, structural problems, and environmental factors. Ovulation occurs once a month between the time of menarche and menopause. The release of a mature egg from the ovary is controlled with the hypothalamic-pituitary-ovarian axis. Several hormones such as gonadotropin-releasing hormone (GnRH), FSH (follicle-stimulating hormone), LH (luteinizing hormone), estrogen, and progesterone play fundamental roles in the ovulation process. Both FSH and LH are the main treatment for women with ovulation disorders. Depending on the reasons for infertility, several different types of treatment are available for infertile women. Fertility drugs as an important part of treatment work like the natural hormones to treat infertility. Several fertility drugs can regulate ovulation and the release of an egg from the ovary in women with polycystic ovary syndrome (PCOS) or undergoing in vitro fertilization (IVF) treatment. This mini-review is about the FDA-approved prescription drugs that induce ovulation in women with ovulatory problems.

Hormonal medication in medically assisted reproduction: a systematic review of assessments from patients.

Several hormonal fertility medications have comparable effectiveness. A literature review was conducted into patients' assessments regarding seven medication characteristics including 'side effects' and 'ease of use'. Medline, CINAHL and PsycINFO were searched for female fertility patients' written assessments of a hormonal medication. The tools used were appraised and common (i.e. ≥10%) unpleasant consequences were distinguished from rare ones. The 35 eligible studies did not rely on valid and reliable tools and did not provide patient assessments regarding all seven medication characteristics for any of the globally used medications. Evidence on medications for oocyte triggering was absent and for induction of pituitary quiescence it was scarce. Regarding medications for ovarian stimulation and luteal support, evidence on general side effects (mostly headache), local side effects (mostly pain), 'interference with home life' and 'impact on psychological wellbeing' was found. Evidence on 'ease of use' and 'required education' was only identified for medication for ovarian stimulation. Evidence on 'interference with work life' and 'compliance worry' was absent. This review calls for randomized controlled trials questioning patients with valid and reliable tools. In the meantime, this review's summary of the best available evidence can be integrated in decision aids facilitating personalized and informed medication choices.

Is it ethical to provide IVF add-ons when there is no evidence of a benefit if the patient requests it?

In vitro fertilisation (IVF) 'add-ons' are therapeutic or diagnostic tools developed in an endeavour to improve the success rate of infertility treatment. However, there is no conclusive evidence that these interventions are a beneficial or effective adjunct of assisted reproductive technologies. Additionally, IVF add-ons are often implemented in clinical practice before their safety can be thoroughly ascertained. Yet, patients continue to request and pay large sums for such additional IVF tools. Hence, this essay set out to examine if it is ethical to provide IVF add-ons when there is no evidence of a benefit if the patient requests it. In order to determine what is ethical-namely, morally good and righteous, the question was considered in relation to three key values of medical ethics-autonomy, beneficence and non-maleficence. It was determined that providing IVF add-ons might be morally acceptable in specific circumstances, if true informed consent can be given, there is a potential of cost-effective physiological or psychological benefit and the risk of harm is minimal, particularly with regard to the unborn child.

Trimester-specific phthalate concentrations and glucose levels among women from a fertility clinic.

BACKGROUND: Subfertile women are at increased risk of glucose intolerance in pregnancy. Based on epidemiologic studies, exposure to certain phthalates is associated with diabetes, elevated glucose, and increased insulin resistance. OBJECTIVES: To evaluate the association between urinary phthalate metabolites and pregnancy glucose levels in women seeking medically assisted reproduction. METHODS: We evaluated 245 women participating in a prospective cohort study based at a large fertility clinic who delivered live births and had data on pregnancy urinary phthalate metabolite concentrations and blood glucose levels. Urinary phthalate metabolite concentrations were from single spot urine samples collected in 1st and 2nd trimesters. Blood glucose data was abstracted from medical records for non-fasting 50-g glucose challenge tests at 24-28 weeks gestation. Multivariable linear regression models were used to evaluate associations between 7 urinary phthalate metabolites in quartiles and mean glucose adjusted for potential confounders. RESULTS: Eighteen percent of women had glucose levels ≥ 140 mg/dL. Second trimester monoethyl phthalate (MEP) concentrations were positively associated with glucose levels, with adjusted mean (95%CI) glucose levels of 121 mg/dl (114, 128) vs. 109 mg/dL (103, 116) for women in highest and lowest quartiles, respectively. Women in the highest quartile of second trimester mono-isobutyl phthalate (MiBP) concentrations had a mean glucose level 14 mg/dL lower compared to women in the lowest quartile. No other urinary phthalate metabolites were associated with glucose levels. CONCLUSIONS: MEP and MiBP-metabolites of diethyl phthalate and dibutyl phthalate, respectively-were associated with higher pregnancy glucose in subfertile women-a population at high risk of glucose intolerance in pregnancy.

What are the best predictors for successful GnRH antagonist protocol in in vitro fertilization (IVF) treatment?

OBJECTIVE: To determine factors that affect the success rate of GnRH antagonist protocol in in vitro fertilization (IVF) treatment. DESIGN: Retrospective cohort study. PATIENTS: Patients who underwent IVF cycle with their first GnRH antagonist protocol. INTERVENTION: Antagonist protocol during IVF treatment. The main outcome measurements were; Number of retrieved oocytes, embryo quality and pregnancy rate. RESULTS: Gravidity was negatively correlated with number of eggs (p = 0.017), while total follicle number ≥15 (p = 0.044) and E(2) on day of human chorionic gonadotropin (HCG) (p = 0.000) had a positive correlation with number of eggs. Maximum follicle size at HCG administration showed a trend toward an inverse correlation (p = 0.053). Addition of LH to drug stimulation was negatively correlated with number of eggs in comparison to rFSH only (p = 0.013 and 0.0000, respectively). Age and number of frozen eggs were negatively correlated with successful pregnancy (p = 0.025 and 0.004, respectively), while embryo quality, gravidity and number of embryos were positive (p = 0.011 and 0.014, respectively). CONCLUSION: Controlled parameters like timing of antagonist start, duration of antagonist and the optimal leading follicle diameter for HCG triggering had no effect on treatment outcomes.

Immunomodulatory and clinical effects of the "tiaomian III decoction" in patients with blood blocking antibody deficiency and recurrent spontaneous abortion.

We studied the immunomodulatory and clinical effects of the empirical formula "tiaomian III decoction" on maternal blood blocking antibody deficiency and recurrent spontaneous abortion. Sixty-one patients with blocking antibody deficiency were divided in the experimental group (N = 31), who took tiaomian III decoction, and the control group (N = 30), who received active immunotherapy with paternal lymphocytes; both treatments lasted 3 months. Blocking antibodies, anti-idiotypic antibodies, interleukin, T-lymphocyte subsets, and macrophage colony-stimulating factor (M-CSF) were tested. After treatment, the positive conversion rate reached 87.1 and 86.7% in the experimental and control groups, respectively. After treatment, CD4 levels decreased while CD8 levels increased in both groups. The CD4/CD8 ratio was higher than normal and increased significantly from pre-treatment (P < 0.05). IL-10 and M-CSF levels increased significantly in both groups (P < 0.05). The 1-year conception rates of the experimental and control groups were 58.1 and 46.7%, respectively (P < 0.05). The results show the tiaomian III decoction can increase the positive conversion rate of maternal blocking antibodies and promote the production of IL-10 and M-CSF. Thus, it strengthens the maternal body's protection of the fetus and maintenance of conception. The higher conception rate of the experimental group demonstrates the positive clinic efficacy of the tiaomian III decoction on maternal blood blocking antibody deficiency and recurrent spontaneous abortion.

[Qilin Pills combined with clomiphene for idiopathic oligoasthenozoospermia].

OBJECTIVE: To observe the therapeutic effect of Qilin Pills combined with clomiphene on idiopathic oligoasthenospermia. METHODS: We randomly assigned 300 patients with idiopathic oligoasthenospermia to a trial (n = 156) and a control group (n = 144) to be treated with Qilin Pills (6 g, tid) combined with clomiphene (50 mg, qd) and clomiphene alone (50 mg, qd), respectively, both for a course of 12 weeks. Before and after 4, 8, and 12 weeks of medication, we determined sperm concentration, the percentages of grade a and grade a + b sperm, sperm motility, and the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T), followed by evaluation of the clinical efficacy of Qilin Pills with the pregnancy rate in the patients' spouses as the secondaty therapeutic indexes. RESULTS: Compared with the baseline, both groups of patients showed remarkably improved semen parameters and hormone levels after treatment (all P < 0.01). After 4, 8, and 12 weeks of medication, statistically significant differences were observed between the trial and control groups in sperm concentration ([17.06 ± 2.24] vs [15.07 ± 2.48], [22.10 ± 2.65] vs [18.11 ± 2.97], and [28.13 ± 3.59] vs [21.21 ± 3.60] x 10(6)/mL, P < 0.01), the percentage of grade a sperm ([15.03 ± 2.39] vs [13.08 ± 2.51], [21.08 ± 3.16] vs [16.04 ± 3.05], and [28.08 ± 4.70] vs [20.14 ± 4.74]%, P < 0.01), the percentage of grade a + b sperm ([30.10 ± 5.07] vs [26.21 ± 3.96], [38.08 ± 5.64] vs [30.07 ± 4.80], and [48.04 ± 6.49] vs [35.28 ± 4.77]%, P < 0.01), sperm motility ([42.04 ± 4.86] vs [40.29 ± 4.19], [52.05 ± 5.58] vs [48.03 ± 4.40], and [65.03 ± 5.13] vs [56.67 ± 4.99]%), the FSH level ([7.75 ± 1.38] vs [7.20 ± 1.17], [10.83 ± 1.23] vs [9.10 ± 1.32], and [14.22 ± 0.84] vs [12.06 ± 1.45] IU/L, P < 0.01), the LH level ([10.05 ± 1.68] vs [9.18 ± 1.54], [13.96 ± 1.68] vs [11.99 ± 1.71], and [19.01 ± 2.42] vs [15.86 ± 2.08] IU/L, P < 0.01) and the T level ([19.19 ± 192] vs [18.34 ± 1.79] [21.06 ± 1.63] vs [20.06 ± 1.56], and [24.63 ± 1.06] vs [22.03 ± 1.49] nmol/L, P < 0.01). The pregnancy rate in the patients' spouses was significantly higher in the trial than in the control group at 4, 8, and 12 weeks (1.92 vs 0.69, 4.81 vs 3.47, and 11.54 vs 8.33%, P < 0.01). There were no statistically significant differences in drug tolerance between the two groups (P > 0.05). No obvious adverse reactions were observed. CONCLUSION: Qilin Pills combined with clomiphene can evidently improve the seminal quality and hormone level of oligoasthenospermia patients with no obvious adverse events. However, its long-term efficacy and tolerance deserve further clinical investigation.

Use of fertility treatments in relation to the duration of pregnancy attempt among women who were trying to become pregnant and experienced a live birth.

The purpose of this study was to compare the utilization of medical help for fertility among women who reported up to a year versus more than a year of trying to become pregnant and to describe the characteristics of those women seeking early treatment. Data from the 2004-2008 Pregnancy Risk Assessment Monitoring System (PRAMS) survey were used to assess attempt duration and use of fertility treatments in a sample of 9,517 women who had a recent live birth in Utah. PRAMS respondents who were trying to become pregnant at the time of conception were asked questions about fertility treatments (sampling n = 5,238; representative n = 153,036). Univariate and bivariate analyses were used to describe and compare characteristics of women who sought treatment after attempting pregnancy for a year or less and women who waited at least a year to seek treatment. Among women who were trying to become pregnant, 9.5 % reported using some medical assistance to conceive. Among the women trying to become pregnant, 89.3 % had been trying for ≤12 months and 10.7 % reported having tried >12 months. 5.2 % of those trying to become pregnant for up to a year reported use of fertility treatment, compared with 45.8 % of those trying for a year or more. Women who had previous live births were significantly more likely to use early treatment than nulliparous women (aOR = 2.4, 95 % CI = 1.5, 3.9). The use of fertility drugs and other treatments were more common than ART among recipients of early treatment (aOR = 3.7, 95 % CI = 1.7, 7.9). Some women may be receiving fertility treatment before it is clinically indicated. Instead of invasive treatment, these women may benefit from preconception counseling on folic acid, healthy prepregnancy weight and use of ovulation monitoring to time intercourse.

Fertility drugs and cancer: a guideline.

Methodological limitations in studying the association between the use of fertility drugs and cancer include the inherent increased risk of cancer in women who never conceive, the increased risk of cancer because of factors (endometriosis and unopposed estrogen) associated with infertility, the low incidence of most of these cancers, and that the diagnosis of cancer is typically several years after fertility drug use. On the basis of available data, there does not appear to be an association between fertility drugs and breast, colon, or cervical cancer. There is no conclusive evidence that fertility drugs increase the risk of uterine cancer, although women with infertility are at higher risk of uterine cancer. There are insufficient data to comment on the risk of melanoma and non-Hodgkin lymphoma associated with fertility drug use. Women should be informed that there may be an increased risk of invasive and borderline ovarian cancers and thyroid cancer associated with fertility treatment. It is difficult to determine whether this risk is related to underlying endometriosis, female infertility, or nulliparity.

Efficient production of offspring from Japanese wild-derived strains of mice (Mus musculus molossinus) by improved assisted reproductive technologies.

Because the genetic diversity of the laboratory mouse (Mus musculus) is very limited, wild-derived strains from this genus could provide invaluable experimental models for studies of mouse genetics and epigenetics such as quantitative trait locus analysis. However, such strains generally show poor reproductive performance under conventional husbandry conditions, so their use for large-scale analyses has been limited. This study was undertaken to devise assisted reproductive technologies (ARTs) for the efficient production of offspring in two wild-derived strains, MSM/Ms and JF1/Ms (Mus musculus molossinus). First, as females of these strains are poor responders to equine chorionic gonadotropin (eCG) stimulation, we examined the efficiency of superovulation by injecting anti-inhibin serum followed by human chorionic gonadotropin (hCG). Approximately four to six times more oocytes were ovulated than with eCG-hCG treatment in both strains, reaching ∼25-30 oocytes per female. Consequently, the procedures for in vitro fertilization using these superovulated oocytes and cryopreservation of embryos and spermatozoa could be optimized for both of the wild-derived strains. However, MSM/Ms embryos but not JF1/Ms embryos failed to develop to term after embryo transfer because of intrauterine death at mid to late gestation. We were able to overcome this obstacle by cotransfer of these embryos with those from laboratory strains combined with treatment of recipient females with an immunosuppressant (cyclosporin A). Thus, a series of ARTs essential for efficient production and preservation of the wild-derived strains were successfully devised. These technologies will facilitate systematic studies of mouse genetics and epigenetics using a wider range of genetic diversity than currently available in the genus Mus.

Ultra-Long GnRH Agonist Protocol During IVF/ICSI Improves Pregnancy Outcomes in Women With Adenomyosis: A Retrospective Cohort Study.

Objective: This study aimed to compare the ultra-long gonadotropin-releasing hormone agonist (GnRH-a) protocol and the long GnRH-a protocol during in vitro fertilization (IVF) or intracytoplasmic sperm (ICSI) treatment on fertility outcomes in women with adenomyosis. Materials and Methods: This study was a retrospective cohort study. From January 2011 to May 2018, a total of 371 fresh IVF/ICSI cycles were included. Among the cycles included, 237 cycles of 212 women underwent the ultra-long GnRH-a protocol, while 134 cycles of 116 women underwent the long GnRH-a protocol. The rates of implantation, clinical pregnancy per embryo transfer, live birth, and early miscarriage were estimated between the compared protocols. Results: In the study, the early miscarriage rate in women undergoing the ultra-long GnRH-a protocol was significantly lower than those undergoing the long GnRH-a protocol (12.0% versus 26.5%, p = 0.045), whereas the differences in the rates of biochemical pregnancy, implantation, clinical pregnancy, and live birth in women between the two groups showed no statistical significance. The pregnancy outcomes were also sub-analyzed according to the adenomyotic region (diffuse and focal). As for diffuse adenomyosis, the rates of clinical pregnancy and live birth in women undergoing the ultra-long GnRH-a protocol were significantly higher than those undergoing the long GnRH-a protocol (55.3% versus 37.9%, p = 0.025; 43.4% versus 25.9%, p = 0.019, respectively). However, pregnancy outcomes showed no difference between the two protocols in women with focal adenomyosis. Conclusions: The ultra-long GnRH-a protocol during IVF/ICSI improves pregnancy outcomes in women with adenomyosis, especially in women with diffuse adenomyosis when compared with the long GnRH-a protocol.

Use of Fertility Drugs and Risk of Malignant Melanoma: Results from a Large Danish Population-Based Cohort Study.

Fertility drugs have not definitively been linked to malignant melanoma. By the use of data from a large nationwide cohort of women aged 20.0-45.0 years and living in Denmark between January 1, 1995 and December 31, 2011, we assessed the association between the use of fertility drugs and the risk of malignant melanoma. Information on fertility status and the use of fertility drugs was obtained from the population-based Danish Infertility Cohort. Cox proportional hazard regression models were applied to estimate hazard ratios and 95% confidence intervals with adjustment for potential confounders. The study population comprised 1,330,954 women, of whom 86,231 (6.5%) were treated with fertility drugs. During a median follow-up of 21.0 years, 6,139 women were diagnosed with malignant melanoma. Compared with fertile women, women with fertility challenges who had used any fertility drugs had an increased risk of malignant melanoma (hazard ratio = 1.14; 95% confidence interval = 1.02-1.27). Furthermore, the use of specific types of fertility drugs (clomiphene, gonadotropins, human chorionic gonadotropin, gonadotropin-releasing hormone preparations, and progesterone) was also associated with an increased risk of malignant melanoma, with hazard ratios ranging between 1.09 and 1.13; however, the association did not reach statistical significance. Our findings indicate that the use of fertility drugs was associated with a modestly increased risk of malignant melanoma.

Roles of melatonin in the field of reproductive medicine.

Melatonin, mostly released by the pineal gland, is a circadian rhythm-regulated and multifunctional hormone. Great advances in melatonin research have been made, including its role in rhythms of the sleep-wake cycle, retardation of ageing processes, as well as antioxidant or anti-inflammatory functions. Melatonin can scavenge free radicals such as reactive oxygen species (ROS), a key factor in reproductive functions. Melatonin plays an important role in oocyte maturation, fertilization and embryonic development as well. The concurrent use of melatonin increases the number of mature oocytes, the fertilization rate, and number of high-quality embryos, which improves the clinical outcome of assisted reproductive technology (ART). This review discusses the relationship between melatonin and human reproductive function, and potential clinical applications of melatonin in the field of reproductive medicine.

A review for physiological activities of EGCG and the role in improving fertility in humans/mammals.

Epigallocatechin-3-gallate (EGCG) is a secondary metabolite in green tea, which has various physiological activities, including antioxidant, antitumor, and antiviral activities. Studies have shown that EGCG has a preventive effect on infertility by protecting germ cells and oocytes from damage. EGCG functions mainly through the regulation of ROS (reactive oxygen species) levels, which affect the expression of catalase (CAT), superoxide dismutase 1(SOD1), superoxide dismutase 2(SOD2), and glutathione peroxidase (GPx), has positive influence on other enzyme activities in germ cells and oocytes, and actively alters antioxidant activities. These enzymes above can inhibit the activation of extracellular signal-regulated proteins (Erk), induce apoptosis, and control the production of ROS in tissue cells. Here, we present a comprehensive overview of the mechanisms underlying the main physiological activities of EGCG, including antioxidant, antitumor, and antiviral activities, and their potential roles in male and female reproductive systems and fertility. This paper discusses the mechanisms by which EGCG retards the infertility of germ cells and oocytes and provides a supportive recommendation for improving fertility in humans and animals. We hope it will provide useful references for related research in mammalian reproduction.

Endometrial compaction before frozen euploid embryo transfer improves ongoing pregnancy rates.

OBJECTIVE: To assess whether the calculated difference in endometrial thickness from the end of the estrogen phase to the day of ET (after 6 days of P in hormonally prepared cycles) is associated with ongoing pregnancy rates in euploid frozen ETs (FETs). DESIGN: An observational cohort study. SETTING: Single tertiary care medical center. PATIENT(S): Ultrasound images from 234 hormonally prepared FET cycles were assessed. All the transfers were elective single ETs of a euploid embryo, post-preimplantation genetic testing for aneuploidy (PGT-A). INTERVENTION(S): Ultrasound measurements of peak endometrial thickness at the end of the estrogen phase and again after 6 days of P at the time of ET. MAIN OUTCOME MEASURE(S): Ongoing pregnancy rate in relation to the delta between endometrial thickness at the end of estrogen phase and at the time of ET. RESULT(S): We calculated the ongoing pregnancy rate in cycles where the endometrial lining decreased (compacted) after addition of P by 5%, 10%, 15%, and 20% and demonstrated a significantly higher pregnancy rate after all rates of compaction of the endometrial lining in comparison with cycles where the endometrial lining did not compact. The ongoing pregnancy rate in this cohort, after compaction of 15% or more, was 51.5%, compared with 30.2% in cycles where the endometrial lining did not compact. CONCLUSION(S): There is a significant correlation between endometrial lining compaction and ongoing pregnancy rate in FET cycles of euploid embryos. These findings help to explain why some euploid embryos may fail to implant.

Pregnancy registry: three-year follow-up of children conceived from letrozole, clomiphene, or gonadotropins.

OBJECTIVE: To study the development of children conceived from non-IVF infertility treatments consisting of gonadotropins, clomiphene, or letrozole. DESIGN: Prospective cohort study. SETTING: U.S. academic health centers. PATIENT(S): Children of women with polycystic ovary syndrome who conceived with letrozole (LTZ) or clomiphene (CC) in the PPCOS II study or women with unexplained infertility (AMIGOS study) who conceived with LTZ, CC, or gonadotropin (GN). INTERVENTION(S): Longitudinal annual follow-up from birth to age 3. MAIN OUTCOME MEASURE(S): Scores from Ages and Stages Developmental Questionnaire (ASQ), MacArthur-Bates Communicative Development Inventory (MCDI), and annual growth. RESULT(S): One hundred eighty-five children from 160 families participated in at least one follow-up evaluation from the two infertility trials. Most multiple gestations in the follow-up study resulted from GN treatment (n = 14) followed by CC (n = 6) and LTZ (n = 3). There were no significant differences among the three groups at any time point with respect to abnormal scores on the ASQ. On the MCDI Words and Gestures, the LTZ group scored significantly higher than the GN group for most items (phrases, early gestures, later gestures, and total gestures). Children in the CC group scored significantly higher than the GN group for the later gestures and total gestures items. CONCLUSION(S): Differences in growth and cognitive developmental rates among children conceived with first-line infertility therapies, including LTZ, are relatively minor and likely due to differences in multiple pregnancy rates.