Search

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., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lan, Wu, Wu, Wu, Yang, Liu, Lin, Jiao and Zhang.)

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., (© 2020 Wiley Periodicals, Inc.)

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?

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., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

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., (Copyright © 2020. Published by Elsevier Inc.)

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., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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., (© 2019 UICC.)

A growing list of clinical adjuncts are being used during in vitro fertilization (IVF) treatment. Most of these IVF add-ons (such as growth hormone, aspirin, heparin, dehydroepiandrostenedione, testosterone, male and female antioxidants, and screening hysteroscopy) are being introduced into routine clinical practice in a hurried manner without any clear evidence of benefit in most cases. These add-ons make the IVF more complicated and increase the overall cost for the treatment, which is borne by the couples and health care providers. Our current review found no high-quality evidence to support the use of these IVF add-ons in routine practice. Large, well-designed, randomized trials must be conducted to evaluate the effectiveness and safety of these interventions. There is also a pressing need to develop an evidence-dictated mechanism for introducing newer interventions into routine clinical settings., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The probability of live birth from an in vitro fertilization (IVF) cycle is modest. Many additional treatments (add-ons) are available which promise to improve the success of IVF. This review summarizes the current evidence for common IVF add-ons which are suggested to improve endometrial receptivity. Systematic reviews of randomized controlled trials and individual trials were included. Five add-ons were included: immune therapies, endometrial scratching, endometrial receptivity array, uterine artery vasodilation, and human chorionic gonadotropin instillation. The results suggest there is no robust evidence that these add-ons are effective or safe. Many IVF add-ons are costly, consuming precious resources which may be better spent on evidence-based treatments or further IVF. Large randomized controlled trials and appropriate safety assessment should be mandatory before the introduction of IVF add-ons into routine practice., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Empiric use of medical and nutritional supplements to improve semen parameters and pregnancy rates in couples with idiopathic infertility has reached global proportions, although the evidence base for their use in this setting is controversial., Objective: We systematically reviewed evidence comparing the benefits of nutritional and medical therapy on pregnancy rates and semen parameters in men with idiopathic infertility., Evidence Acquisition: A literature search was performed using MEDLINE, Embase, LILACS, and the Cochrane Library (searched from January 1, 1990 to September 19, 2017). using the methods detailed in the Cochrane Handbook. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess the certainty of evidence., Evidence Synthesis: The literature search identified 5663 citations, and after screening of abstracts and full texts, 61 studies (59 randomised controlled trials and two nonrandomised comparative studies) were included. Pooled results demonstrated that pentoxyfylline, coenzyme Q10, L-carnitine, follicle-stimulating hormone, tamoxifen, and kallikrein all resulted in improvements in semen parameters. Individual studies identified several other medical and nutritional therapies that improved semen parameters, but data were limited to individual studies with inherent methodological flaws. There were limited data available on live birth and pregnancy rates for all interventions. The GRADE certainty of evidence for all outcomes was very low mainly owing to methodological flaws and inconsistencies in study design. Some outcomes were also downgraded owing to imprecision of results., Conclusions: There is some evidence that empiric medical and nutritional supplements may improve semen parameters. There is very limited evidence that empiric therapy leads to better live birth rates, spontaneous pregnancy, or pregnancy following assisted-reproductive techniques. However, the findings should be interpreted with caution as there were some methodological flaws, as a number of studies were judged to be either at high or unclear risk of bias for many domains., Patient Summary: This review identified several medical and nutritional treatments, such as pentoxyfylline, coenzyme Q10, L-carnitine, follicle-stimulating hormone, tamoxifen, and kallikrein, that appear to improve semen parameters. However, there are limited data suggesting improvements in pregnancy and live birth rates. The lack of evidence can be attributed to methodological flaws in studies and the low number of pregnancies reported., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Subfertility is common and affects one in six couples, half of whom lack an explanation for their delay in conceiving. Developments in the diagnosis and treatment of subfertility over the past 50 years have been truly remarkable. Indeed, current generations of couples with subfertility are more fortunate than previous generations, as they have many more opportunities to become parents. The timely access to effective treatment for subfertility is important as many couples have a narrow window of opportunity before the age-related effects of subfertility limit the likelihood of success. Assisted reproduction can overcome the barriers to fertility caused by tubal disease and low sperm count, but little progress has been made in reducing the effect of increasing age on ovarian function. The next 5-10 years will likely see further increases in birth rates in women with subfertility, a greater awareness of lifestyle factors and a possible refinement of current assisted reproduction techniques and the development of new ones. Such progress will bring challenging questions regarding the potential benefits and harms of treatments involving germ cell manipulation, artificial gametes, genetic screening of embryos and gene editing of embryos. We hope to see a major increase in fertility awareness, access to safe and cost-effective fertility care in low-income countries and a reduction in the current disparity of access to fertility care.

Background: Previous reports on effect of antioxidants on sperm DNA integrity were equivocal, and there is a lack of randomized, placebo-controlled studies., Objectives: To evaluate the efficacy of combined antioxidant treatment in subfertile men with normal reproductive hormone levels and high sperm DNA fragmentation index (DFI)., Materials and Methods: This placebo-controlled, double-blind, randomized study evaluated the effects of combined antioxidant treatment in 77 men from infertile couples, with normal testosterone, LH and FSH levels and DFI ≥25%. All participants were randomly assigned to receive combined antioxidant treatment (vitamins, antioxidants and oligoelements) or placebo for six months. The primary outcome measured was DFI. Secondary outcomes were standard semen parameters. DFI and other semen parameters were, at each time point (pre-treatment, and after three and six months of treatment), compared between the treatment and the placebo group using Mann-Whitney U-test., Results: Antioxidant group had higher sperm concentration after three months of treatment (median: 24.4 × 10 6 /mL vs. 27.2 × 10 6 /mL; P = 0.028) and borderline statistically significant higher concentration after six months of treatment (median: 24.4 × 10 6 /mL vs. 33.3 × 10 6 /mL; P = 0.053) compared to pre-treatment values. The DFI did not change during the 6 months of antioxidant therapy. No statistically significant difference between the antioxidant and placebo group was seen for any of the semen parameters including sperm DFI at any of the three time points., Discussion: The increase in sperm concentration was more pronounced in the antioxidant treated group but not statistically significantly higher than among controls, perhaps due to insufficient statistical power. Previous studies have shown positive effect of antioxidant treatment on DFI and other semen parameters. However, our findings indicate that men with normal reproductive hormone levels may not be the primary target group for such therapy., Conclusion: Six months treatment with antioxidants had no effect on sperm DFI., (© 2018 American Society of Andrology and European Academy of Andrology.)

We aimed to examine the effects of infertility treatments on the risk of Autism Spectrum Disorder (ASD). Data were from a representative national registry on 110,093 male live births in Israel (born: 1999-2008; and ASD: 975, 0.9%). Infertility treatments included In Vitro Fertilization (IVF), and five hormone treatments. Relative risk (RR) was estimated with multivariable logistic models. Results showed that IVF treatment compared with spontaneous conception was not statistically significantly associated with the risk of ASD. Only progesterone hormone treatment was associated with a statistically significant (p < .05) increased risk of ASD (RR = 1.51, 95% CI 1.22, 1.86) compared to the group with no progesterone treatment. In conclusion, progesterone exposure during the critical period of fetal life elevated the risk of ASD, possibly reflecting epigenetic modification., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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.

Personalized medicine has many definitions. This term is often used synonymously with precision medicine, which is defined as the classifying patients with a disease or condition based on their phenotypic findings, such as biomarkers or genomics, into subpopulations that differ in their response to a specific treatment. Personalized medicine, however, can also mean the treatment of individual patients based on many contextual factors, such as response to therapy and patient preferences, in addition to predefined phenotypic findings. Regulatory approval for the marketing of a new drug or a new indication for a marketed drug requires a positive benefit risk profile and substantial evidence of effectiveness. The indication is based on the eligibility criteria and outcomes of the clinical trial(s) underpinning the regulatory approval. For precision medicine, drugs are often developed with companion diagnostics that are necessary for selection of the subgroup of patients, in contrast to personalized medicine which may be directed at a single patient. Most drugs are approved with a fixed dosage regimen for the approved population, but some drugs and biologics are approved with instructions to tailor therapy for individual patients, whether it be dosing, combination with other therapies, or selection among a class of medications. Hence, more often than not, personalized medicine directed at individual patients is achieved through the practice of medicine rather than regulatory action., (Published by Elsevier Inc.)

Associations have been demonstrated between fertility drugs and a variety of hormone-sensitive carcinomas. The purpose of this study was to determine the relationship between fertility drugs used in the treatment of female infertility and the risk of thyroid cancer. To investigate the clinical significance of fertility drugs used for the treatment of female infertility and the risk associated with thyroid cancer, we performed a literature search using PubMed, MEDLINE, the Cochrane Library, the Web of Science, and EBSCOHOST for comparative studies published any time prior to July 21, 2017. The studies included women who were treated for infertility with fertility drugs, such as clomiphene citrate, gonadotropins, or other unspecified fertility agents, which reported the incidence of thyroid cancer as the main outcome. Eight studies were included in the meta-analyses. Among women with infertility, there was a significant positive association between thyroid cancer risk and the use of fertility drugs (relative risk [RR] = 1.35; 95% confidence interval [CI] 1.12-1.64; P = 0.002). Additionally, among women with infertility, the use of clomiphene citrate was associated with an increased risk of thyroid cancer compared to women who did not use fertility drugs (RR = 1.45; 95% CI 1.12-1.88; P = 0.005). After pooling results, we found that the parity status of infertile women using fertility drugs was not associated with thyroid cancer risk (RR = 0.99; 95% CI 0.61-1.58, P = 0.95). In summary, clomiphene citrate (the most commonly used fertility drug) and other fertility drugs are associated with an increased risk of thyroid cancer.

Background Walnut leaf is one of the many medicinal plants used in folklore as male fertility enhancers. The present work was therefore undertaken with an aim to scientifically validate this claim. As such, we evaluated the effect of the aqueous extract from walnut leaves on biomolecules related to fertility in adult male rats and its mode of action as fertility-enhancing agent. Methods Twenty-five rats were randomly divided into five groups of five animals each; Group 1 served as control and received normal (0.9%) saline only; Groups II, III, IV received 50, 500, 1,000 mg/kg body weight (BW) of T. conophorum leaf extract orally, while Group V served as standard and was given suspension of clomiphene citrate orally at the dose of 1.04 mg/kg/ml BW. The extract and drug were given daily and the experiment lasted for 21 consecutive days. Results The testicular biochemical parameters in treated groups showed significant (p<0.05) increase in lactate dehydrogenase activity activity, Glucose-6-phosphate dehydrogenase (G-6PDH) activity, glycogen content, 3β and 17β hydroxysteroid dehydrogenase activities and testicular and epididymal Zn and Se contents with a significant decrease in cholesterol content. A significant increase in testis weight and epididymis weight were also observed. Also, a significant (p<0.05) increase in the level of serum testosterone, luteinizing hormone (LH), follicle-stimulating hormone, sperm count, motility, viability and a decrease in sperm abnormality were observed in the various treated groups when compared with the control group. This increment was concentration dependent, while the extract at the highest concentration showed a more pronounced effect than the standard drug. Also, no sperm DNA fragmentation index was found in all the treatment groups. Photomicrographs from light and scanning electron microscopy showed large fenestrae of interstitial tissue, large fluid space and intact seminiferous epithelium layers fully packed with spermatogenic cells in treated groups than the control group. Conclusions The present study has demonstrated that Tetracarpidium conophorum leaf possesses fertility-enhancing property and have useful effects on spermatogenesis and sperm parameters in rats.

Increasing evidence disclosed the existence of a novel multi-organ endocrine pathway, involving bone, pancreas and testis, of high penetrance in energy metabolism and male fertility. The main mediator of this axis is undercarboxylated osteocalcin (ucOC), a bone-derived protein-exerting systemic effects on tissues expressing the metabotropic receptor GPRC6A. The recognized effects of ucOC are the improvement of insulin secretion from the pancreas, the amelioration of systemic insulin sensitivity, in particular in skeletal muscle, and the stimulation of the global endocrine activity of the Leydig cell, including vitamin D 25-hydroxylation and testosterone production. The supporting evidence of this circuit in both animal and human models is here reviewed, with particular emphasis on the role of ucOC on testis function. The possible pharmacological modulation of this hormonal circuit for therapeutic aims is also discussed., (© 2017 American Society of Andrology and European Academy of Andrology.)

The hypothalamic-pituitary-gonadal axis controls reproduction via a series of hormones regulating gonadal function through interconnected feedback loops. Secretion of hypothalamic-derived gonadotropin-releasing hormone (GnRH) integrates inputs from higher brain centers to coordinate the activity of the pituitary gonadotrope and the biosynthesis and secretion of the gonadotropins which ultimately regulate gonadal function. Failure of GnRH to serve as the central integrator of this system has been associated with hypogonadotropic-hypogonadism and clinical infertility, while pharmacological application of GnRH analogs and gonadotropins have important implications of the treatment of such infertility. Furthermore, the GnRH-GnRH receptor system has been characterized in several types of cancer and may offer therapeutic possibilities in their treatment. Given the central role of GnRH action in the control of fertility, it is of paramount importance to understand the molecular basis of control of GnRH action in the pituitary gonadotrope, including new and novel alternate ways to modulate GnRH action and gonadotropin secretion. The goal of this review is to discuss several new findings in this field focusing on novel regulators of GnRH action., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Some 15% of all couples in the industrialized world suffer from infertility. Accordingly, any possible life-long morbidity that may result from treatments for infertility presents a significant concern to public health. The use of medications for infertility is specifically relevant to their possible effects on the classical target tissues for hormones involved in the sex axes, i.e., uterus, ovaries, and breast, but may have an effect on other organs, which harbor receptors for some of the hormones involved in reproduction. When one deals with the effect of treatment for infertility on the occurrence of malignant conditions, there is no doubt that certain malignancies tend to occur more frequently in women who suffered from and/or were treated for infertility., Objective: To review the accumulated data on the association of treatments for infertility with subsequent malignancies both in the classical target organs of sex steroids and in non-target organs., Methods: Systematic compilation of the relevant literature., Results & Conclusion: Contrary to popular believes, treatment for infertility is associated with very little increase in malignacies.

Male infertility contributes to a substantial share to couple infertility. Despite scientific efforts, most cases of male infertility remain 'idiopathic' and male-specific therapeutic options are sparse. Given the crucial role of the follicle-stimulating hormone (FSH) for spermatogenesis, FSH is used empirically to improve semen parameters. Furthermore, a recently updated Cochrane review points to a beneficial effect of FSH treatment in idiopathic infertile men on spontaneous pregnancy rates. However, since response to FSH varies strongly even in selected patients and given the lack of powerful evidence of FSH treatment regimens, intra-cytoplasmic spermatozoa injection (ICSI) is widely used in idiopathic male infertility, though the treatment burden is high for the couple and it entails considerable costs and some risks. Single nucleotide polymorphisms (SNPs) within FSH ligand/receptor genes (FSHB/FSHR), significantly influencing reproductive parameters in men, represent promising candidates to serve as pharmacogenetic markers to improve prediction of response to FSH. However, there is an evident lack of information which patients should be treated and how many patients in an andrological outpatient clinic would be eligible for such a treatment, a crucial decision criterion for clinicians and also pharmaceutical industry to start such a pharmacogenetic intervention therapy. After screening our andrological patient cohort, we present a realistic scenario and a basis for further prospective studies using FSH in idiopathic infertile men., (© 2015 American Society of Andrology and European Academy of Andrology.)

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.

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.

Oxidative stress, decreased antioxidant capacity, and impaired sperm mitochondrial function are the main factors contributing to male infertility. The goal of the present study was to assess the effect of the per os treatment with Carni-Q-Nol (440 mg L-carnitine fumarate + 30 mg ubiquinol + 75 IU vitamin E + 12 mg vitamin C in each softsule) in infertile men on sperm parameters, concentration of antioxidants (coenzyme Q10,  CoQ(10-TOTAL), γ, and α-tocopherols), and oxidative stress in blood plasma and seminal fluid. Forty infertile men were supplemented daily with two or three Carni-Q-Nol softsules. After 3 and 6 months of treatment, improved sperm density was observed (by 48.9% and 80.9%, resp.) and after 3-month treatment the sperm pathology decreased by 25.8%. Concentrations of CoQ(10-TOTAL) (ubiquinone + ubiquinol) and α-tocopherol were significantly increased and the oxidative stress was decreased. In conclusion, the effect of supplementary therapy with Carni-Q-Nol showed benefits on sperm function in men, resulting in 45% pregnancies of their women. We assume that assessment of oxidative stress, CoQ(10-TOTAL), and α-tocopherol in blood plasma and seminal fluid could be important metabolic biomarkers in both diagnosis and treatment of male infertility.

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.

Reduced fertility is one of the main long-term consequences of chemotherapy given for lymphoma, leukemia, and other malignancies in young women. We examined with a female rat model whether and how dienogest, a fourth-generation progestin, modulates reduced fertility following exposure to gonadotoxic chemotherapy. Female rats were administered cyclophosphamide with or without GnRH agonist and different concentrations of dienogest for 20 days. Animals were sacrificed on Day 29, and the numbers of follicle at primordial, preantral and antral stage in the ovaries were counted histologically. Rats treated with sterile saline solution (as control), cyclophosphamide, cyclophosphamide plus GnRH agonist, and cyclophosphamide plus dienogest were also mated with male rats to evaluate their fertility and pregnancy outcomes. Cyclophosphamide significantly reduced the number of primordial follicles, whereas dienogest suppressed depletion of primordial follicle pool induced by chemotherapy. Although the rats exposed to cyclophosphamide alone failed to deliver live births, co-treatment with dienogest improved the pregnancy outcomes of treated rats. The protective effect of dienogest on chemotherapy-induced ovarian damage and reduced fertility was comparable to that of GnRH agonist. The present results suggest that the co-administration of dienogest and chemotherapy may be a useful strategy in preserving ovarian function and fertility in premenopausal women facing gonadotoxic chemotherapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In recent years, the negative impact of oxidative stress on fertility has become widely recognised. Several studies have demonstrated its negative effect on the number and quality of retrieved oocytes and embryos following in-vitro fertilisation (IVF). Melatonin, a pineal hormone that regulates circadian rhythms, has also been shown to exhibit unique oxygen scavenging abilities. Some studies have suggested a role for melatonin in gamete biology. Clinical studies also suggest that melatonin supplementation in IVF may lead to better pregnancy rates. Here we present a critical review and summary of the current literature and provide suggestions for future well designed clinical trials.

In vitro fertilization (IVF) is expensive, time consuming, and the most successful treatment of fertility; however, in general the cumulative chance of having a live birth with the treatment is still around 40%. Many couples still remain unsuccessful after several IVF attempts, causing deep impact on quality of life, and each failed cycle causing a financial burden. Several adjuvant therapies have been used along with IVF to increase the pregnancy rates for women with repeated implantation failure. Testing of adjuvant therapies in properly conducted randomized controlled trials is rarely done so that potential benefits and risks are unlikely to be clearly presented to patients and clinicians. In this review, we assessed the effects of adjuvants, such as growth hormone, androgens, and glucocorticoids to enhance oocyte number and quality; sildenafil, low-dose aspirin, heparin, corticosteroids, granulocyte colony-stimulating factor, endometrial injury, intrauterine injection of human chorionic gonadotropin, and intrauterine administration of autologous peripheral blood mononuclear cells to improve poor endometrial response; antioxidants, complementary and alternative medicine modalities, such as Chinese herbal medicine and acupuncture; and assisted hatching and preimplantation genetic screening to correct embryonic factors., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Idiopathic male infertility can be diagnosis in approximately one-third of infertile males. The empirical medical treatment with or without assisted reproductive techniques appears common in male infertility practice. This type of management can be classified as hormonal treatment including gonadotropins, antiestrogens, and aromatase inhibitors and support with antioxidant supplements such as carnitine, lycopene, glutathione, and vitamin E. This review investigates the evidence of commonly used empirical medical management of male infertility when there is no demonstrable diagnosis., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Food and drug supplements (FDS) are extensively used by infertile couples either to supplement medical infertility treatment and assisted conception or as a means to independently improve conception rates. The majority of FDS are composed of antioxidants that are used for male and female infertility. Their use, despite being biologically plausible, lacks scientific support due to limitations stemming from poorly designed small studies. FDS and for that matter complementary and alternative medicine (CAM) is plagued by fallacies that confuse or mislead the public and thus may prevent many patients from making the right therapeutic decisions regarding their infertility problem. We do concur that the absence of evidence is not the evidence of absence; however, one should be wary of the apparent benign effects of FDS and CAM. The current literature seems to suggest a beneficial effect of antioxidants on male infertility. There is, however, no FDS that has been proven beyond doubt to increase conception rates in female infertility. The additive value of CAM and FDS on the success of assisted conception is also not known. Well-designed randomized studies are urgently needed given the popularity and ever increasing consumption of these supplements by the infertile couples., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

This report describes a successful pregnancy and delivery following oocyte activation with strontium chloride (SrCl2) in couples with repeated complete fertilization failure or low fertilization rates even after calcium ionophore treatment. Eight infertile couples who showed complete fertilization failure or low fertilization rates after conventional intracytoplasmic sperm injection (ICSI) and calcium ionophore treatment. When the results of fertilization were not satisfactory in the cycles, the oocytes were artificially activated by SrCl2 for the next attempts. Oocyte activation with SrCl2 significantly increased the fertilization rates, when compared with conventional ICSI or calcium ionophore treatment (61.7% vs. 20.0% or 25.3%, respectively). There was significant increase in the proportions of good-quality cleaved embryos (50.0% vs. 0% or 12.5%, respectively). The rate of surplus embryos that developed to blastocyst stage increased in SrCl2-treated oocytes, when compared with that in ICSI with or without calcium ionophore treatment (25.7% vs. 0% or 9.1%, respectively). Five successful pregnancies were attained after oocyte activation with SrCl2, of which eight healthy children were born. Physical and mental development of the children were normal from birth to 60 months. These results suggest that SrCl2 in treatment should be considered as an effective method for artificial oocyte activation (AOA) to improve fertilization rates and embryo quality in cases with complete fertilization failure or low fertilization rates after calcium ionophore treatment.

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.

Objective: To determine the degree of improvement in semen parameters after finasteride discontinuation., Design: A prospective database of men presenting for a fertility evaluation was analyzed for semen and hormone parameters before and after discontinuation of finasteride., Setting: A male infertility specialty clinic., Patient(s): Men presenting for fertility evaluation from 2008-2012 on finasteride., Intervention(s): None., Main Outcome Measure(s): Semen and hormone parameters before and after discontinuation of finasteride., Result(s): At presentation, 27 (0.6%) of 4,400 men on finasteride. The mean duration of treatment with finasteride was 57.4 months, and mean dose was 1.04 mg/day. There was an average 11.6-fold increase in sperm counts after finasteride discontinuation. Of the men with severe oligospermia (<5 M/mL), 57% had counts increase to >15 M/mL after finasteride cessation. No man had a decrease in sperm count. There was no change in hormone parameters, sperm motility, or sperm morphology., Conclusion(s): Finasteride, even at low doses, may cause reduced sperm counts in some men. In this population, counts improved dramatically for the majority of men after finasteride discontinuation. The hormone parameters, sperm motility, and sperm morphology were unchanged after cessation. Finasteride should be discontinued in subfertile men with oligospermia, and used with caution in men who desire fertility., (Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

In recent years, there has been an increase in the diagnosis of infertility. In industrialized countries, approximately 15% of couples experience this problem today, with a negative impact on quality of life. For this reason, assisted reproductive technologies and other treatments, finalized to overcome infertility, have become very common in clinical practice. For a long time, different ovulation-inducing drugs have been used for ovarian follicle stimulation, either as independent therapies or treatments used during in vitro fertilization cycles. Despite this long-term use, the medical care for infertility gave rise to a lively debate about the potential risk of developing breast cancer that has never been settled. Many studies have been conducted to address this question; but their results have been, and still are, contradictory. The aim of this review is to determine the potential link between the use of fertility drugs and the risk of developing breast cancer in women treated for infertility.

Objective: To analyze pregnancy outcomes in young women with stage IA, grade 1 endometrioid adenocarcinoma of the uterus after successful fertility-sparing management using progestin., Methods: We reviewed the medical records of 141 women with stage IA, grade 1 endometrioid adenocarcinoma of the uterus who had complete remission after progestin treatment. Statistical analysis was performed using Student's t test or Mann-Whitney U test for continuous variables, using χ or Fisher's exact test for categorical variables, and using log-rank test for survival comparison., Results: Fifty-four (38.3%) women in the study cohort had a history of infertility. Seventy (49.6%) of the 141 patients tried to conceive with 44 (62.9%) receiving fertility drugs. The median interval to attempted pregnancy after treatment was 5 months (range 1-31 months). The median age at the time of the pregnancy trial was 32.4 years (range 23-40 years). Fifty-one (73%) of 70 women who tried to conceive were successful and 46 (66%) gave birth to 58 live neonates. The spontaneous abortion rate, ectopic pregnancy rate, and preterm delivery rates in our cohort were 24%, 2.8%, and 11.5%, respectively. The 5-year disease-free survival was similar between patients who received fertility drugs (n=44) or who did not (n=97) (73% compared with 62%, P=.335), and this rate was significantly higher in patients who achieved at least one pregnancy (n=51) than those who did not (n=90) (76% compared with 62%, P=.028)., Conclusions: Although the proportion of patients with a history of subfertility or infertility was high in our cohort, the pregnancy outcomes were very promising using assisted reproductive technology. The use of fertility drugs was not associated with a higher incidence of cancer recurrence after successful fertility-sparing management in this study population., Level of Evidence: II.

Treating the infertile client with competence and compassion is within the scope of practice for advanced practice clinicians. However, due to both a lack of emphasis on infertility treatment in many advanced practice education programs and confusion regarding diagnosis and treatment by many practitioners, infertility is often undertreated by these providers. A basic infertility evaluation, patient counseling, and prescriptive therapy with oral ovulation-inducing agents by a knowledgeable practitioner is cost-effective and may result in successful pregnancy in women who otherwise may not be adequately and quickly treated prior to referral to a reproductive endocrinologist. A diagnosis of infertility is often stressful and frustrating for a couple. Midwives and advanced practice nurses are uniquely qualified to provide both compassionate care and competent treatment during this time. This article provides the clinician with an overview of infertility diagnosis, evaluation, and initial management with lifestyle modifications and oral ovulation-inducing agents., (© 2012 by the American College of Nurse-Midwives.)

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.

The evaluation of cancer risk among patients treated for infertility is complex, given the need to consider indications for use, treatment details, and the effects of other factors (including parity status) that independently affect cancer risk. Many studies have had methodologic limitations. Recent studies that have overcome some of these limitations have not confirmed a link between drug use and invasive ovarian cancers, although there is still a lingering question as to whether borderline tumors might be increased. It is unclear whether this merely reflects increased surveillance. Investigations regarding breast cancer risk have produced inconsistent results. In contrast, an increasing number of studies suggest that fertility drugs may have a special predisposition for the development of uterine cancers, of interest given that these tumors are recognized as particularly hormonally responsive. Additional studies are needed to clarify the effects on cancer risk of fertility drugs, especially those used in conjunction with in vitro fertilization. Because many women who have received such treatments are still relatively young, further monitoring should be pursued in large well-designed studies that enable assessment of effects within a variety of subgroups defined by both patient and disease characteristics., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Justicia insularis T. Anders (Acanthaceae) is a medicinal plant whose leaves and those of three other plants are mixed for the preparation of a concoction used to improve fertility and to reduce labour pains in women of the Western Region of Cameroon. Previous studies have demonstrated the inducing potential on ovarian folliculogenesis and steroidogenesis of the aqueous extract of the leaf mixture (ADHJ) of four medicinal plants (Aloe buettneri, Dicliptera verticillata, Hibiscus macranthus and Justicia insularis) among which the later represented the highest proportion. This study was aimed at evaluating the ovarian inducing potential of J. insularis in immature female rats. Various doses of the aqueous extract of J. insularis were daily and orally given, for 20 days, to immature female rats distributed into four experimental groups of twenty animals each. At the end of the experimental period some biochemical and physiological parameters of ovarian function were assayed. The administration of the aqueous extract of Justicia insularis significantly induced an early vaginal opening in all treated groups (P < 0.001) as well as an increase (at doses of 50 or 100 mg/kg) in the number of hemorrhagic points, Corpus luteum, implantation sites, ovarian weight, uterine and ovarian proteins. Ovarian cholesterol level (P < 0.05) significantly decreased in animals treated with the lowest dose (12.5 mg/kg). The evaluation of the toxicological effects of the extract on pregnancy showed that it significantly increased pre- and post-implantation losses, resorption index and decreased the rate of nidation as well as litter's weight. These results suggest that the aqueous extract of Justicia insularis induces ovarian folliculogenesis thus justifying its high proportion in the leaf mixture of ADHJ.

Objectives: To assess the effect of Traditional Chinese Herbal Medicine (CHM) in the management of female infertility and on pregnancy rates compared with Western Medical (WM) treatment., Methods: We searched the Medline and Cochrane databases and Google Scholar until February 2010 for abstracts in English of studies investigating infertility, menstrual health and Traditional Chinese Medicine (TCM). We undertook meta-analyses of (non-)randomised controlled trials (RCTs) or cohort studies, and compared clinical pregnancy rates achieved with CHM versus WM drug treatment or in vitro fertilisation (IVF). In addition, we collated common TCM pattern diagnosis in infertility in relation to the quality of the menstrual cycle and associated symptoms., Results: Eight RCTs, 13 cohort studies, 3 case series and 6 case studies involving 1851 women with infertility were included in the systematic review. Meta-analysis of RCTs suggested a 3.5 greater likelihood of achieving a pregnancy with CHM therapy over a 4-month period compared with WM drug therapy alone (odds ratio=3.5, 95% CI: 2.3, 5.2, p<0.0001, n=1005). Mean (SD) pregnancy rates were 60±12.5% for CHM compared with 32±10% using WM drug therapy. Meta-analysis of selected cohort studies (n=616 women) suggested a mean clinical pregnancy rate of 50% using CHM compared with IVF (30%) (p<0.0001)., Conclusions: Our review suggests that management of female infertility with Chinese Herbal Medicine can improve pregnancy rates 2-fold within a 4 month period compared with Western Medical fertility drug therapy or IVF. Assessment of the quality of the menstrual cycle, integral to TCM diagnosis, appears to be fundamental to successful treatment of female infertility., (Copyright © 2011 Elsevier Ltd. All rights reserved.)