Exogenous Progesterone Research Articles

Treatment of Low-Risk Endometrial Cancer and Complex Atypical Hyperplasia With the Levonorgestrel-Releasing Intrauterine Device.

To assess efficacy of the levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of complex atypical hyperplasia or low-grade endometrial cancer. This retrospective case series included all patients treated with the LNG-IUD for complex atypical hyperplasia or early-grade endometrial cancer from January 2003 to June 2013. Response rates were calculated and the association of response with clinicopathologic factors, including age, body mass index, and uterine size, was determined. Forty-six patients diagnosed with complex atypical hyperplasia or early-grade endometrial cancer were treated with the LNG-IUD. Of 32 evaluable patients at the 6-month time point, 15 had complex atypical hyperplasia (47%), nine had G1 endometrial cancer (28%), and eight had grade 2 endometrial cancer (25%). Overall response rate was 75% (95% CI 57-89) at 6 months; 80% (95% CI 52-96) in complex atypical hyperplasia, 67% (95% CI 30-93) in grade 1 endometrial cancer, and 75% (CI 35-97) in grade 2 endometrial cancer. Of the clinicopathologic features evaluated, there was a trend toward the association of lack of exogenous progesterone effect in the pathology specimen with nonresponse to the IUD (P=.05). Median uterine diameter was 1.3 cm larger in women who did not respond to the IUD (P=.04). Levonorgestrel-releasing IUD therapy for the conservative treatment of complex atypical hyperplasia or early-grade endometrial cancer resulted in return to normal histology in a majority of patients.

Effect of exogenous progesterone on cumulus characteristics of buffalo oocytes by allowing passage of more number of sperm through cumulus but not essentially fertilization

Objective: To understand the level of progesterone (P4) in different quality of buffalo cumulus oocyte complexes (COCs) and further to evaluate the effect of exogenous P4 supplementation on maturation and subsequent developmental ability of poor quality brilliant cresyl blue (BCB- ) COCs. Methods: Progesterone secreted by different quality of buffalo oocytes was estimated by enzyme linked immunosorbent assay and the concentration differences were translated into P4 doses to be incorporated in the maturation medium of BCB-ve COCs followed by expression analysis of genes involved in the cumulus expansion, extracellular matrix disintegration and progesterone receptor signalling. In addition, the study also evaluated the effect of exogenous P4 on sperm-cumulus interaction. Results: More than 10-fold up- regulated expression of progesterone receptor in P4 supplemented oocytes signified that P4 might be acting predominantly through this receptor. Also, exogenous P4 supplementation had significant effect on transcatheter arterial chemoembolization protease regulated by P4- progesterone receptor pathway which in turn had an important role in extracellular matrix disintegration. On the contrary, cumulus expansion genes HAS2, TNFAIP6, AREG were not altered upon P4 supplementation. Also, it was observed that P4 addition did facilitate passage of significantly more number of spermatozoa through P4 treated cumulus cells. Further, incorporation of different doses of P4 did not improve significantly the cleavage and blastocyst rates of BCB-ve COCs. Conclusions: Different qualities of buffalo COCs secrete substantially diverse levels of P4, and its supplementation has a role in oocyte maturation via modulation of cumulus characteristics but perhaps not fertilization.

Effect of Exogenous Progesterone or Flunixin Meglumine After AI on Serum Progesterone Concentration and Pregnancy per AI in Lactating Dairy Cows.

The objective of this study was to determine the effect of post AI administration of exogenous progesterone (P4) or a prostaglandin F2α (PGF2α) synthesis inhibitor agent on serum P4 concentrations and pregnancy per AI (P/AI) in lactating dairy cows. Eighty lactating cows were randomly allocated to one of four treatment groups: 1) CON (control), received 5 mL of saline solution on d 6 and 14 post AI; 2) IP4 (injection of P 4), received 125 mg of P4 im on d 6 and 14 post AI; 3) CIDR, received a controlled internal drug release insert containing 1.38g of P4 from d 6 to 20 post AI; and 4) FM (Flunixin Meglumine), received 0.625 g of Flunixin Meglumine, a nonsteroidal anti-inflammatory drug, twice daily on d 15 and 19 post AI. Blood samples were taken on d 0, 6, 14, 17 and 20 post AI to determine P4 concentrations. Transrectal palpation was performed between 40 and 45 d post AI to determine pregnancy status. All treatment groups (i.e. IP4, CIDR and FM) resulted in greater serum P4 concentration on d 17 and 20 post AI compared to CON (P < 0.05). Cows given a CIDR insert had greater concentrations of P 4 on d 17 and 20 than IP4 and FM cows (P < 0.05). However, no significant difference was found between IP4 and FM groups for serum P4 concentrations. The P/AI was greater (P < 0.05) in CIDR-treated cows (55%, 11/20) than CON (25%, 5/20), and intermediate in IP4 (40%, 8/20) and FM (35%, 7/20) cows. In summary, treatment with exogenous P4 (i.e. CIDR and IP4) or FM increased serum P4 concentrations in lactating dairy cows. However, results suggest that only CIDR administration would improve P/AI.

Biotransformation of progesterone by the ascomycete Aspergillus niger N402

The ability of the ascomycete Aspergillus niger N402 to transform exogenous progesterone was investigated. We found that this strain has steroid-hydroxylating activity and can introduce a hydroxyl group into the progesterone molecule mainly at positions C11(α) and C21 with predominant formation of 21-hydroxyprogesterone (deoxycortone). In addition, formation of 6β,11α-dihydroxyprogesterone was also observed. Studying the effects of the growth medium composition and temperature on progesterone conversion by A. niger N402 showed that the most intense accumulation of 21-hydroxyprogesterone occurred in minimal synthetic medium at 28°C. Increasing the cultivation temperature to 37°C resulted in almost complete inhibition of the hydroxylase activity in the minimal medium. In the complete medium, a similar increase in temperature inhibited 11α-hydroxylase activity and completely suppressed 6β-hydroxylase activity, but it produced no effect on 21-hydroxylating activity.

Timing of exogenous progesterone administration is critical for embryo development and uterine gene expression in an ovine model of maternal constraint.

Progesterone (P4) administration in early pregnancy enhances embryo growth in sheep but is associated with decreased embryo survival. This study examined the effects of exogenous P4 administered during specific time periods between pregnancy Day 0 and Day 6 to determine the critical time point for advancement of embryo growth without pregnancy loss and to examine Day 6 and Day 19 endometrial gene expression. Suffolk (S) embryos were transferred into Cheviot (C) ewes that received exogenous P4 (CP4) on Days 0-3 (CP40-3), Days 0-6 (CP40-6), Days 2-4 (CP42-4) or Days 3-6 (CP43-6). Additionally, S embryos were transferred to C and S ewes that did not receive P4 (CnP4 and SnP4). Day 19 embryos from CP4 ewes were longer (P<0.05) than those from CnP4 ewes. CP42-4 ewes had embryos of similar size to those of CP40-3 and CP40-6 ewes but had higher pregnancy rates. There was altered expression of genes associated with embryo implantation and histotroph production: diacylglycerol-O-acyltransferase (DGAT2), hepatocyte growth factor (HGF) and prostaglandin endoperoxide synthase 2 (PTSG2) on Day 6 and endometrial galectin 15 (LGALS15) and mucin glycoprotein 1 (MUC1) on Day 19. This suggests that specific timing of P4 administration is critical to the enhanced embryo growth and survival observed. These findings provide a platform for further investigation aimed at advancing embryo development and survival.

Effect of exogenous progesterone on embryo size and ewe uterine gene expression in an ovine 'dam size' model of maternal constraint.

Progesterone (P4), acting via its receptor, regulates uterine function and histotroph production, which are crucial to embryo growth. This study aimed to examine exogenous P4 effects on embryo size and differential endometrial gene expression at Day 19 of gestation using a 'dam size' sheep model of maternal constraint. Purebred Suffolk (S, genotypically large) embryos were transferred into recipient groups of Cheviot (C, genotypically small) or Suffolk ewes that had, or had not, been pre-treated with P4 from Days 0 to 6 of pregnancy. At Day 19S embryos were collected from four experimental groups: P4 pretreated S ewes (SP4; n=5), untreated S ewes (SnP4; n=15), P4 pretreated C ewes (CP4; n=7) and untreated C ewes (CnP4; n=21). Day-19 embryos from CP4 ewes were larger (P<0.05) than those from CnP4 ewes and similar in size (P>0.05) to embryos from SnP4 and SP4 ewes. Expression of mucin 1 (MUC1) and prostaglandin-endoperoxide synthase 2 (PTGS2) was upregulated in uterine horns ipsilateral to the corpus luteum from CP4 ewes. Prostaglandin receptor (PGR), MUC1 and PTGS2 expression was upregulated, whilst cathepsin L (CTSL) and radical S-adenosyl methionine domain-containing 2 (RSAD2) expression was downregulated in the ipsilateral horn of SP4 ewes. This suggests that pretreating ewes with exogenous P4 may alleviate early pregnancy maternal constraint via mechanisms that alter uterine function. However, further research is required to investigate the timing of P4 administration and its impact on conception rates.

Progesterone down-regulates SLIT/ROBO expression in mouse corpus luteum

BackgroundProgesterone produced by the corpus luteum (CL) is essential for preparation, implantation and maintenance of gestation. Furthermore, progesterone plays a protective role against luteolysis in rodents. It has been reported that Slit/Robo family members expressed in the CL and involved in prostaglandin F2α (PGF2α) induced luteolysis. However, the interactions between progesterone and Slits/Robos in CL are not clear. This study was designed to examine whether or not luteolysis is regulated by the interaction of progesterone and Slits/Robos in mouse CL. MethodsIn the current study, we used Real-time PCR to identify the effect of progesterone on Slit2/Robo1 expression in cultured luteal cells in vitro, and the exogenous progesterone injection on mouse luteolysis and Slit/Robo expression in vivo was studied via Real-time PCR and Western bolt. ResultsOur in vitro experiment revealed that 1μM progesterone significantly decreased Slit2/Robo1 mRNA levels at 6h, 12h and 24h. Our in vivo experiment showed that the mRNA and protein levels of Slit2 and Robo1 decreased significantly 7days after progesterone supplement. ConclusionThese findings indicate that progesterone maintains CL function and resists luteolysis possibly through down-regulating Slit/Robo signaling pathway in the CL.

Using transrectal ultrasound to examine the effect of exogenous progesterone on early embryonic loss in sheep.

The financial impact of early embryonic loss in Australia may be as high as $137 million AUD/year. Embryos may be lost due to environmental conditions, or maternal factors such as nutrition or progesterone (P4) profiles. However, studies on the supplementation of P4 during early pregnancy have returned contradictory results, partly as a reliable method of detecting embryos in the early stages of gestation (<day 20) has yet be established. As such, Merino ewes (n = 62) were either not supplemented (control) or were given exogenous P4 at the time of insemination (day 0) or 3 days later (day 3). Transrectal ultrasound (TRUS) was performed on day 10, 12, 14, 17, 19 and 29 following laparoscopic artificial insemination. Transcutaneous ultrasound (TCUS) was performed on day 54 to confirm pregnancy and peripheral blood was collected for hormone analysis on day 19 to compare the accuracy of all three pregnancy diagnosis methods. Data were then analysed in developmental periods. The percentage of ewes detected as pregnant by TRUS during pre-, peri- and post implantation was 66% (41/62; day 12 and 14), 61% (38/62; day 17 and 19) and 58% (36/62; day 29), respectively. TCUS during established gestation recorded a pregnancy rate of 60% (37/62). The sensitivity of TRUS to correctly diagnose ewes as pregnant during pre-, peri- and post implantation was 68% (25/37), 89% (33/37) and 100% (36/36), respectively, while the sensitivity to correctly identify multiples was 49% (16/33), 60% (21/35) and 97% (34/35), respectively (P<0.05). The majority of embryonic loss occurred between pre- and peri- implantation (0.9±0.15 per ewe; P<0.001). No further loss was recorded after this point. Ewes that were given P4 at day 0 had significantly higher embryonic loss (77%) compared to the control (52%) and day 3-ewes (56%; P<0.05). These results show TRUS is a viable tool for investigating early embryonic loss and that the variability noted in previous P4 supplementation studies may be due to variation in time and length of treatment.

Effect of exogenous progesterone administration on luteal sensitivity to PGF during the early development of the corpus luteum in mares and cows.

The objective of this study was to determine the effect of exogenous progesterone administration at ovulation and during the early development of the CL, on its future sensitivity to a single administration of PGF2a in mares and cows. Horse Retrospective reproductive data from an equine clinic in the UK during three breeding seasons were used. Mares were divided into: control group, cycles with single ovulations; double ovulation group cycles with asynchronous double ovulations; and PRID group: cycles with single ovulations and treatment with intravaginal progesterone device (CIDR) immediately after the ovulation. All mares were treated with d-cloprostenol (PGF) at either: (i) 88hr; (ii) 96hr; (iii) 104hr; or (iv) 112hr after the last ovulation. Cattle A total of nine non-lactating Holstein cows were used. All cows were administered PGF14 d apart and allocated to one of two groups control group GnRH was administered 56hr after the second PGF administration. CIDR group CIDR was inserted at the same time of GnRH administration. All cows were administered PGF at 120hr post-ovulation. The complete luteolysis rate of mares with double ovulation (66.7%) and those treated with exogenous progesterone (68.4%) was significantly higher than the rate of mares with single ovulation (35.6%) at 104hr. In the cow, however, the treatment with CIDR did not increase the luteolytic response in cows treated at 120hr post-ovulation. In conclusion, the degree of complete luteolysis can be influenced by increasing the concentration of progesterone during the early luteal development in mares.

PR-Set7 deficiency limits uterine epithelial population growth hampering postnatal gland formation in mice.

Formation of secretary endometrial glands in the uterus known as adenogenesis is a typical process of branching morphogenesis involving dynamic epithelial growth and differentiation. Unsuccessful adenogenesis often leads to female infertility. However, it remains largely unexplored so far regarding the epigenetic machinery governing normal endometrial gland formation. Here, we demonstrated that PR-Set7, an epigenetic regulator for H4K20me1 modification, was extensively expressed in the postnatal uteri, and its conditional deletion resulted in a complete lack of endometrial glands and infertility in mice. Subsequent analysis revealed that uterine PR-Set7 deficiency abolishes the dynamic endometrial epithelial population growth during the short span of gland formation from postnatal days 3 to 9. This markedly reduced epithelial population growth in PR-Set7-null mutant uteri is well associated with DNA damage accumulation and massive apoptotic death in the epithelium, due to blockade of 53BP1 recruitment to DNA damage sites upon reduced levels of H4K20me1/2. Using PgrCre/+/Rosa26DTA/+ mouse line and postnatal progesterone injection mouse model, we further confirmed that an impaired epithelial cell population growth either by inducing epithelial death in the diphtheria toxin-A (DTA)-mouse model or attenuating epithelial growth upon postnatal progesterone treatment similarly hampers uterine adenogenesis. Collectively, we establish here a novel 'epithelial population growth threshold' model for successful gland development. Besides further shedding light on the regulatory machinery governing uterine gland formation, our findings raise a safety concern on progesterone supplementation to prevent preterm birth in women bearing a female fetus, as exogenous progesterone may hamper uterine adenogenesis via attenuating epithelial population growth.

Postpartum Changes in Mood and Smoking-Related Symptomatology: An Ecological Momentary Assessment Investigation.

Postpartum smoking relapse is a highly prevalent public health problem. Mood and breast feeding are significantly associated with smoking relapse, although less is known about the temporality of these relationships. Therefore, this study utilized ecological momentary assessments (EMA) to prospectively examine changes in mood and smoking-related symptomatology in relationship to three events-childbirth, termination of breast feeding, and smoking relapse. We expected all three events to significantly alter mood and smoking-related symptomatology. We enrolled a sample of pregnant women who had recently quit smoking and intended to remain quit during the postpartum. Participants were randomized to active/placebo progesterone to prevent postpartum relapse. Participants also completed daily EMA to collect data mood and smoking-related symptomatology as well as our three events of interest. Participants (n = 46) were, on average, 26.5 ± 0.8 years old and, prior to pregnancy, smoked 10.1 ± 0.7 cigarettes/day. We noted a number of significant within- and between-subject relationships. For example, participants reported a 24% decline in negative affect after childbirth (p = .0016). Among those who relapsed to smoking (n = 23), participants randomized to placebo had a significant increase in cigarette craving after relapse (β = 1.06, 95% confidence interval [CI] = 0.62 to 1.49, p value = .0003), whereas participants randomized to active progesterone did not (β = 0.63, 95% CI = -0.35 to 1.62, p value = .1824). These observations suggest that mood and smoking-related symptomatology are influenced by childbirth, breast feeding, smoking relapse, and use of exogenous progesterone. Future research should explore how these observations may inform novel postpartum smoking relapse-prevention interventions. Postpartum smoking relapse has been a persistent public health problem for more than 40 years. Although a number of significant predictors of postpartum smoking relapse have been identified (eg, depression and breast feeding), much of these analyses have relied on cross-sectional and/or self-reported retrospective data. Therefore, for the first time, we utilized ecological momentary assessment to explore the effect of childbirth, termination of breast feeding, and smoking relapse on mood and smoking-related symptomatology (eg, craving). Numerous significant relationships were observed, including a 96% increase in craving after smoking relapse. These novel observations can inform new and effective postpartum smoking relapse-prevention programs.

Live birth rates and safety profile using dydrogesterone for luteal phase support in assisted reproductive techniques.

Assisted reproductive techniques (ARTs) result in a deficient luteal phase, requiring the administration of intramuscular, intravaginal or oral exogenous progesterone. Dydrogesterone, an oral retroprogesterone with good bioavailability, has been used in assisted reproductive cycles with outcomes that are comparable to those of vaginal or intramuscular progesterone. However, there are limited reviews on its use for luteal phase support in ARTs, in terms of pregnancy outcomes and associated fetal anomalies. This study aimed to review the live birth rates and associated fetal anomalies of women who were given dydrogesterone for luteal phase support in assisted reproductive cycles at a tertiary hospital in Singapore. This retrospective descriptive study included 1,050 women who underwent in vitro fertilisation/intracytoplasmic sperm injection at the Centre for Assisted Reproduction of Singapore General Hospital between 2000 and 2011. The women were given dydrogesterone for luteal phase support. The main outcome measures were rates of pregnancy, live birth, miscarriage and fetal anomalies. The pregnancy and live birth rates were 34.7% and 27.7%, respectively. Among those who achieved pregnancy, 17.0% miscarried, 0.8% had ectopic pregnancies and 0.3% had molar pregnancies. Fetal anomalies were detected in 1.9% of pregnancies, all of which were terminated by choice. Since the outcomes of dydrogesterone are comparable to those of intramuscular and vaginal progesterone, it is a reasonable option to provide luteal phase support for women who are uncomfortable with injections or vaginal insertions. Randomised controlled studies are needed to determine the optimal dosage of dydrogesterone for luteal phase support in ARTs.

Exogenous progesterone is neuroprotective following injury to the male zebra finch brain.

The use of progesterone following brain injury has a controversial history. On one hand, some lab-based models have showed progesterone as being neuroprotective, but on the other, clinical trials have showed quite the opposite. One of many complaints that arose from this discrepancy was the lack of a diverse pool of animal models and paradigms employed during the preclinical phase. However, over the past decade, the zebra finch has emerged as an optimal organism for the study of steroid-mediated neuroprotection. Following an injury, steroid hormones and receptors are upregulated, serving to decrease neuroinflammation and overall damage to the brain. As compared to other vertebrate models, zebra finches can upregulate expression of both estrogens and androgens at a faster and more robust response, suggesting that vertebrates differ in their neuroprotective mechanisms and timing following injury. Therefore, to expand the types organisms studied in pre-clinical trials, we chose to use zebra finches. While the majority of work in the zebra finch brain has focused on estrogens and androgens, we sought to clarify the role of progesterone following injury. Adult male zebra finches were given daily injections of progesterone following a penetrating injury and then were assessed for the size of injury and expression of various genes associated with neuroinflammation and cell survival. Treatment with progesterone decreased the injury size in zebra finches over controls and increased expression of various genes associated with cell survival and neuroinflammation. These data suggest that progesterone does mediate neuroprotection, most likely through the alteration of neuroinflammatory and cell survival pathways.

Increased Incidence of Endometrial Cancer Following the WHI: An Assessment of Risk Factors [18OP

INTRODUCTION: The US incidence of Type I Endometrial cancer (EC) dramatically increased following the Women’s Health Initiative (WHI). While most cancer rates are decreasing, EC incidence increased from 2003 to 2013. EC rates were stable 1992 to 2002, prior to the announcement of WHI results. Potential etiologies for this increase are examined, including compounded hormone therapy use, which may not provide adequate endometrial protection. METHODS: EC incidence was obtained from Surveillance, Epidemiology, and End Result Program database from 1975 through 2013. The incidence of risk factors thought to be associated with EC, including age, obesity, race, number of menstrual cycles, gravidity and parity, metabolic syndromes (diabetes mellitus, PCOS), diet and exercise, and medications (hormone therapy including FDA-approved and unapproved [compounded] estrogens and progesterone, tamoxifen, and hormonal contraceptives) were evaluated and temporal trends were compared to EC trends. RESULTS: Endometrial cancer rates were constant from 1992 to 2002 in women 50-74 years of age, but have increased 2.5% annually with a 10% increase from 2006 to 2012 (test for trend 0.82). The greatest percentage of new cases was in women 55-64 years of age. Use of estrogen and progestin combinations have decreased while risk factors remained constant or decreased during the same time; however, obesity and compounded hormone use have increased coincident with the EC increase. CONCLUSION: EC increased post-2002 following the WHI, which may be multifactorial. The combination of an increase in obesity concurrent with decreasing exogenous progesterone and an increase in compounded hormone therapy is a public health issue requiring further evaluation.

Progestogen Hypersensitivity: Heterogeneous Manifestations with a Common Trigger

Hypersensitivity to progestogen, previously known as autoimmune progesterone dermatitis, is an increasingly recognized clinical entity that presents specific diagnostic and treatment challenges. Clinical presentations are heterogeneous, but can consist of hypersensitivity symptoms associated with the progesterone surge during the luteal phase of the menstrual cycle or after exposure to exogenous progestins. With the increasing use of exogenous progesterone for contraception and fertility, more cases of hypersensitivity to exogenous progestins have been described. Here we will review proposed pathomechanisms for progestogen hypersensitivity (PH) as well as the clinical presentation of PH, testing strategies to aid in diagnosis, and treatment options for patients with hypersensitivity to progestogens.

Progesterone Decreases in vitro Indoleamine 2, 3-dioxygenase Expression in Dendritic and CD4+ Cells from Maternal-Fetal Interface of Rats

ABSTRACTProblem: Several mechanisms contribute to the tolerogenic state observed during pregnancy, such as the activity of the enzyme indoleamine 2, 3-dioxygenase (IDO). This initializes the catabolism of tryptophan, inducing T cells to apoptosis due to its deprivation and by the action of its catabolites in the placental microenvironment. Progesterone plays an important part on immunological tolerance mechanisms during pregnancy; however, there is no evidence it is related to IDO activity. Thus, this study aimed to investigate progesterone influence on the maternal-fetal interface of pregnant Wistar rats, by identifying IDO positive cells by immunophenotyping and flow cytometry under exogenous progesterone supplementation.Method of study: Placenta and embryo cells were cultured and separated into groups that received interferon γ or progesterone, supplemented or not with mifepristone. After 2 and 24 h, these were labeled with an anti-IDO and a series of antibodies specific to leucocytes and progesterone receptor and processed through flow cytometry analysis.Results: Progesterone induced a significant decrease in the expression of IDO in dendritic cells and CD4+ lymphocytes.Conclusion: The blocking of progesterone receptor on these cells by mifepristone restored IDO expression levels and may constitute evidence of the participation of this hormone through a direct route in these cells.

Prenatal Exposure to Progesterone Affects Sexual Orientation in Humans.

Prenatal sex hormone levels affect physical and behavioral sexual differentiation in animals and humans. Although prenatal hormones are theorized to influence sexual orientation in humans, evidence is sparse. Sexual orientation variables for 34 prenatally progesterone-exposed subjects (17 males and 17 females) were compared to matched controls (M age=23.2years). A case-control double-blind design was used drawing on existing data from the US/Denmark Prenatal Development Project. Index cases were exposed to lutocyclin (bioidentical progesterone=C21H30O2; M W : 314.46) and no other hormonal preparation. Controls were matched on 14 physical, medical, and socioeconomic variables. A structured interview conducted by a psychologist and self-administered questionnaires were used to collect data on sexual orientation, self-identification, attraction to the same and other sex, and history of sexual behavior with each sex. Compared to the unexposed, fewer exposed males and females identified as heterosexual and more of them reported histories of same-sex sexual behavior, attraction to the same or both sexes, and scored higher on attraction to males. Measures of heterosexual behavior and scores on attraction to females did not differ significantly by exposure. We conclude that, regardless of sex, exposure appeared to be associated with higher rates of bisexuality. Prenatal progesterone may be an underappreciated epigenetic factor in human sexual and psychosexual development and, in light of the current prevalence of progesterone treatment during pregnancy for a variety of pregnancy complications, warrants further investigation. These data on the effects of prenatal exposure to exogenous progesterone also suggest a potential role for natural early perturbations in progesterone levels in the development of sexual orientation.

Development and validation of an objective method for the assessment of body condition scores and selection of beef cows for timed artificial insemination

The objectives of this study were to: 1) evaluate the relationship of the angle formed between the left and right sides of the rump with body condition score (BCS) in cattle; and 2) develop an objective tool to select cows for timed artificial insemination (TAI) based on their BCS. In Experiment 1, 801 lactating Nelore cows, 3–12 years old and weighing 400–625kg were enrolled. All females were evaluated according to BCS (scale 1–5). In addition, the angle formed between both sides of the rump was measured in all cows with a goniometer. The relationship between BCS and the rump angle was analyzed by linear regression. There was a positive relationship between BCS and rump angle (P<0.0001). The linear regression equation was angle =77.76+9.94 x BCS; R2=0.67. The aim of Experiment 2 was to evaluate BCS in a simple, direct and objective way using rump angle and related BCS to TAI performance. A device was developed called Vetscore® to determine BCS according to rump angle. Using the Vetscore, cows were classified into three different categories of BCS using a color-based method: red, BCS<2.75; green, BCS between 2.75 and 4.5; and yellow, BCS>4.5. A total of 429 Nelore suckling cows, 4–8 years old, were subjected to a TAI protocol based on estradiol benzoate, exogenous progesterone, prostaglandin F2α, equine chorionic gonadotropin and estradiol cypionate. At Day 0, all cows were evaluated with the Vetscore® and classified according to the device's BCS color scale. Pregnancy diagnosis was performed by ultrasonography 30 d after TAI. Pregnancy per AI (P/AI) was analyzed using the chi-square test. A good level of agreement was observed between Vetscore's scale and visual BCS (82.9%). Cows classified as “green” had higher P/AI than cows classified as “red” and “yellow“ (60.4%, 168 of 278; 42.4%, 61 of 144; and 28.6%, 2 of 7; respectively; P<0.001). These results demonstrate that Vetscore® is an efficient and low-cost methodology for the assessment of BCS and, indirectly, nutritional status of beef cows. Finally, cows classified as adequate according to Vetscore® color scale had higher P/AI at 30 d compared with those considered inadequate.

New stimulation regimens: endogenous and exogenous progesterone use to block the LH surge during ovarian stimulation for IVF.

The advent of embryo and oocyte vitrification today gives reproductive specialists an opportunity to consider new strategies for improving the practice and results of IVF attempts. As the freezing of entire cohorts does not compromise, and may even improve, the results of IVF attempts, it is possible to break away from the standard sequence of stimulation-retrieval-transfer. The constraints associated with ovarian stimulation in relation to the potential harmful effects of the hormonal environment on endometrial receptivity can be avoided. This review will look at the new stimulation protocols where progesterone is used to block the LH surge. Thanks to 'freeze all' strategies, the increase in progesterone could actually be no longer a cause for concern. There are two ways of using progesterone, whether it be endogenous, as in luteal phase stimulation, or exogenous, as in the use of progesterone in the follicular phase i.e. progestin primed ovarian stimulation. A literature search was carried out (until September 2016) on MEDLINE. The following text words were utilized to generate the list of citations: progestin primed ovarian stimulation, luteal phase stimulation, luteal stimulation, duostim, double stimulation, random start. Articles and their references were then examined in order to identify other potential studies. All of the articles are reported in this review. The use of progesterone during ovarian stimulation is effective in blocking the LH surge, whether endogenous or exogenous, and it does not affect the number of oocytes collected or the quality of the embryos obtained. Its main constraint is that it requires total freezing and delayed transfer. A variety of stimulation protocols can be derived from these two methods, and their implications are discussed, from fertility preservation to ovarian response profiles to organization for the patients and clincs. These new regimens enable more flexibility and are of emerging interest in daily practice. However, their medical and economic significance remains to be demonstrated. The use of luteal phase or follicular phase protocols with progestins could rapidly develop in the context of oocyte donation and fertility preservation not related to oncology. Their place could develop even more in the general population of patients in IVF programs. The strategy of total freezing continues to develop, thanks to technical improvements, in particular vitrification and PGS on blastocysts, and thanks to studies showing improvements in embryo implantation when the transfer take place far removed from the hormonal changes caused by ovarian stimulation.

A case of oral desensitization for hypersensitivity to exogenous progesterone

Hypersensitivity reaction to progesterone is a rare pathologic condition which consists of autoimmune response to endogenous progesterone, known as autoimmune progesterone dermatitis, and hypersensitivity reaction to exogenous progestogen. We report the case of a 31-year-old woman with a history of whole body urticaria during exogenous progesterone supplementation for in vi-tro fertilization (IVF). She was admitted to the hospital for the diagnosis and management of progestogen hypersensitivity. An intra-dermal test with progesterone revealed positivity to 5 mg/mL of progesterone. For her next IVF, progesterone desensitization was performed in a method combining oral and intramuscular progesterone administration. After successfully achieving a target dose of 100 mg per day, the route of progesterone administration was converted to intravaginal tablet (90 mg twice a day) without any hypersensitivity reactions. (Allergy Asthma Respir Dis 2017;5:294-297)