Administration Of Exogenous Progesterone Research Articles

Progesterone Hypersensitivity in Assisted Reproductive Technologies: Implications for Safety and Efficacy.

The global rise in the age of childbirth, influenced by changing sociodemographic patterns, has had a notable impact on fertility rates. Simultaneously, assisted reproductive techniques (ARTs) have become increasingly prevalent due to advancements in reproductive medicine. The paper explores the intersection between the surge in ARTs and the rising number of iatrogenic autoimmune progesterone dermatitis (APD). Autoimmune progesterone dermatitis, commonly known as progesterone hypersensitivity, manifests itself as a mucocutaneous hypersensitivity syndrome. It is characterized by a wide range of dermatological symptoms, with urticaria and maculopapular rashes being the most prominent signs. Concurrently, systemic symptoms, such as fever, angioedema, and, in severe instances, anaphylaxis, may ensue. This dermatologic condition poses a significant challenge to women of childbearing age. This intricate syndrome frequently manifests itself in conjunction with menstruation or pregnancy as a reaction to physiological fluctuations in endogenous progesterone. However, given that exposure to exogenous progesterone is an integral component of various modern therapies, secondary APD has also been described. Our findings unveil a heightened likelihood of developing secondary progesterone hypersensitivity in ART patients that is attributed to the administration of exogenous progesterone through intramuscular, intravaginal, and oral routes. The study also explores available therapeutic interventions for facilitating viable pregnancies in individuals grappling with autoimmune progesterone dermatitis within the context of ARTs. This comprehensive analysis contributes valuable insights into the intricate relationship between reproductive technologies, dermatological challenges, and successful pregnancy outcomes.

Ендогенна та екзогенна нейростероїдна модуляція пам’яті щурів з алкогольною залежністю та агресивним типом поведінки

Alcoholism and chronic stress lead to impaired cognitive functions, which are regulated, in particular, by neurosteroid hormones. Exogenous administration of progesterone is one of the ways to influence the brain system of hormonal and neurotransmitter regulation. The effect of intranasal administration of low doses of progesterone on endogenous neurosteroid modulation of working and spatial memory in male rats with alcohol dependence and aggressive behavior was investigated. Alcohol dependence in male rats was modeled by voluntary intake of bread soaked in ethanol solution at a dose of 1.2 g/kg for 30 days. Aggressiveness was determined using the sensory contact method and the “partition” test. To study memory processes in rats, neuroethological methods of testing working (recognition of new objects) and spatial (orientation in the Barnes maze) memory were used. Progesterone was administered intranasally at a dose of 80 μg per rat for 10 days. Progesterone, testosterone, and cortisol levels were measured in the frontal neocortex (FC), hippocampus, and serum using enzyme-linked immunosorbent assay kits. The stimulatory effect of alcoholization on spatial memory and impairment of working memory in male rats with aggressive behavior was found. Zoosocial conflict on the background of prolonged alcohol consumption leads to impaired object recognition and spatial orientation against the background of neurosteroid imbalance: a decrease in progesterone and testosterone content in the FC, hippocampus, serum, and an increase in cortisol levels in these structures. Intranasal administration of progesterone to rats with alcohol dependence and aggressive behavior offsets the negative effects of confrontational relationships on working memory processes, restores the acquired experience to the baseline (however, the processes of object differentiation remain weakened); leads to improved spatial memory. The favorable effects of progesterone on memory are accompanied by a decrease in the imbalance of hormonal influences in brain structures with the restoration of progesterone and testosterone concentrations in the FC, hippocampus and serum against the background of weakening of stress-induced glucocorticoid activity. Therefore, intranasal administration of low doses of progesterone improves working and spatial memory in male rats with alcohol dependence and aggressive behavior due to the tendency to restore the balance of hormones (progesterone, testosterone, cortisol) in the brain structures responsible for memory.

Comparison between Agonist Trigger with HCG Luteal Phase Supplementation vs HCG Trigger with Progesterone Luteal Phase Supplementation in Antagonist Controlled Hyperstimulation Cycle Regarding Clinical Pregnancy Rate

For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the comparison between conventional HCG trigger and progesterone luteal phase support vs Agnosit trigger and HCG microsdose luteal phase support as regards to pregnancy rate. Methods 100 patients were recruited for this trial Cases with Polycyctic ovaries were excluded from the study. The study was approved by Ethical committee of Ain Shams university. Patients received Gonal-F (Merck Serono S.p.A., Via delle Magnolie 15, I70026 Modugno (Bari), Italy.) in a dose ranginging between 150-300 IU for stimulation and the dose was adjusted according to response starting day 6. Premature LH surge was prevented with 0.25 mg of a GnRH antagonist (Cetrotide; Merck international) starting on day 6, when two or more follicles reach a size of 18–20 mm, patients were randamized into 2 groups of 50 each. Trigger of ovulation was done by a single dose of 0.2 mg triptorelin (Decapeptyl®ferring pharmaceutical company, Germany) and luteal phase support with daily 125 IU HCG injections in Group 1. Group 2 received A single dose of HCG 10000 IU was given followed by progesterone supplementation with 100mg IM progesterone (Prontogest® IBSA Swisserland). 2 Embryo were transferred and an ultrasound at 4 weeks after embryo transfer for cases with positive pregnancy test. As regards to clinical pregnancy group 1 had 28 of the 50 (56%) Positive clinical pregnancy while control was 26 of the 50 (52%), the difference was not statistically significant (P > 0.68). No cases of moderate or severe ovarian hyperstimulation were observed during the study. To conclude, Agonist trigger combined with microdose HCG had a comparable pregnancy rate resulst to HCG trigger and conventional progesterone support for luteal support without increasing the risk of ovarian hyper stimulation.

Duration of oestrogen exposure does not affect reproductive outcome in artificial cycles: a retrospective analysis of more than 7000 hormonal replacement therapy cycles for an embryo transfer.

Optimal duration of oestrogen exposure before an embryo transfer in artificial cycles has not been defined yet, as its correlation with reproductive outcome remains controversial. The length of oestrogen treatment before starting luteal phase support varies significantly among patients. In this study, we conducted a retrospective analysis of a huge database of our own clinical results in artificial cycles in the past five years. The aim of this study was to assess the effect of the length of estrogen exposure on reproductive outcome and to evaluate if there is any optimal duration of estrogen exposure in order to maximize success rates. Differences in pregnancy rates according to oestrogen length, if present, were not clinically relevant. Our results suggest that the length of oestrogen exposure (in days) before exogenous progesterone administration do not affect clinical outcomes.

The effect of frozen embryo transfer regimen on the association between serum progesterone and live birth: a multicentre prospective cohort study (ProFET).

What is the association between serum progesterone levels on the day of frozen embryo transfer (FET) and the probability of live birth in women undergoing different FET regimens? Overall, serum progesterone levels <7.8 ng/ml were associated with reduced odds of live birth, although the association between serum progesterone levels and the probability of live birth appeared to vary according to the route of progesterone administration. Progesterone is essential for pregnancy success. A recent systematic review showed that in FET cycles using vaginal progesterone for endometrial preparation, lower serum progesterone levels (<10 ng/ml) were associated with a reduction in live birth rates and higher chance of miscarriage. However, there was uncertainty about the association between serum progesterone levels and treatment outcomes in natural cycle FET (NC-FET) and HRT-FET using non-vaginal routes of progesterone administration. This was a multicentre (n = 8) prospective cohort study conducted in the UK between January 2020 and February 2021. We included women having NC-FET or HRT-FET treatment with progesterone administration by any available route. Women underwent venepuncture on the day of embryo transfer. Participants and clinical personnel were blinded to the serum progesterone levels. We conducted unadjusted and multivariable logistic regression analyses to investigate the association between serum progesterone levels on the day of FET and treatment outcomes according to the type of cycle and route of exogenous progesterone administration. Our primary outcome was the live birth rate per participant. We studied a total of 402 women. The mean (SD) serum progesterone level was 14.9 (7.5) ng/ml. Overall, the mean adjusted probability of live birth increased non-linearly from 37.6% (95% CI 26.3-48.9%) to 45.5% (95% CI 32.1-58.9%) as serum progesterone rose between the 10th (7.8 ng/ml) and 90th (24.0 ng/ml) centiles. In comparison to participants whose serum progesterone level was ≥7.8 ng/ml, those with lower progesterone (<7.8 ng/ml, 10th centile) experienced fewer live births (28.2% versus 40.0%, adjusted odds ratio [aOR] 0.41, 95% CI 0.18-0.91, P = 0.028), lower odds of clinical pregnancy (30.8% versus 45.1%, aOR 0.36, 95% CI 0.16-0.79, P = 0.011) and a trend towards increased odds of miscarriage (42.1% versus 28.7%, aOR 2.58, 95% CI 0.88-7.62, P = 0.086). In women receiving vaginal progesterone, the mean adjusted probability of live birth increased as serum progesterone levels rose, whereas women having exclusively subcutaneous progesterone experienced a reduction in the mean probability of live birth as progesterone levels rose beyond 16.3 ng/ml. The combination of vaginal and subcutaneous routes appeared to exert little impact upon the mean probability of live birth in relation to serum progesterone levels. The final sample size was smaller than originally planned, although our study was adequately powered to confidently identify a difference in live birth between optimal and inadequate progesterone levels. Furthermore, our cohort did not include women receiving oral or rectal progestogens. Our results corroborate existing evidence suggesting that lower serum progesterone levels hinder FET success. However, the relationship between serum progesterone and the probability of live birth appears to be non-linear in women receiving exclusively subcutaneous progesterone, suggesting that in this subgroup of women, high serum progesterone may also be detrimental to treatment success. This work was supported by CARE Fertility and a doctoral research fellowship (awarded to P.M.) by the Tommy's Charity and the University of Birmingham. M.J.P. is supported by the NIHR Birmingham Biomedical Research Centre. S.F. is a minor shareholder of CARE Fertility but has no financial or other interest with progesterone testing or manufacturing companies. P.L. reports personal fees from Pharmasure, outside the submitted work. G.P. reports personal fees from Besins Healthcare, outside the submitted work. M.W. reports personal fees from Ferring Pharmaceuticals, outside the submitted work. The remaining authors have no conflict of interest to declare. ClinicalTrials.gov: NCT04170517.

Estrous cycle and hormone regulation of stress-induced reinstatement of reward seeking in female mice

Women are more vulnerable to stress-induced craving, which may be associated with increased vulnerability to relapse. Susceptibility to stress-induced craving also appears to be modulated by the menstrual cycle and is negatively correlated with circulating progesterone levels in women. However, the factors that contribute to relapse vulnerability are poorly characterized in female animals. In this study, we assessed whether chronic ethanol exposure, estrous cycle, or exogenous progesterone administration modulated vulnerability to stress-induced reinstatement. To model ethanol dependence, adult female C57Bl/6J mice underwent chronic intermittent ethanol (CIE) exposure via vapor inhalation. Seventy-two hours after the final ethanol exposure, food-restricted mice began training in a conditioned place preference paradigm (CPP) for a food reward, followed by extinction training. Mice were then subjected to forced swim stress and assessed for reinstatement of their preference for the reward-paired chamber. CIE did not affect stress-induced reinstatement. However, stress-induced reinstatement was attenuated during the diestrus phase, when endogenous levels of progesterone peak in female mice. Further, administration of exogenous progesterone mimicked the attenuated reinstatement observed in diestrus. These findings indicate that circulating hormone levels modulate susceptibility to relapse-like behaviors and implicate progesterone as a potential target for treating stress-induced relapse in women.

Impact of administration route on serum progesterone levels in women undergoing artificial endometrial preparation

ObjectiveAre there differences in serum progesterone levels between different routes of exogenous progesterone administration for artificial endometrial preparation? Material and methodsThis prospective, observational, single-centre study included 9 infertile female patients who underwent cycles of artificial endometrial preparation between January and June 2019 with different progesterone formulations (3 cycles in 2 patients; 2 cycles in 2 patients; and 1 cycle in 5 patients). Oestrogen stimulation was followed by vaginal progesterone 400 mg every 12 h (first cycle), subcutaneous progesterone 25 mg every 12 h (second cycle), and intramuscular progesterone 50 mg every 24 h (third cycle). Progesterone therapy was continued for 5 days and daily serum progesterone was recorded. The primary outcome was day 5 serum progesterone. ResultsDay 5 mean ± standard deviation serum progesterone levels after vaginal, subcutaneous, and intramuscular administration were 14.6 ± 5.5, 47.9 ± 22.3, and 60.3 ± 65.5 ng/mL, respectively (p = 0.032 across routes). From day 1 to day 5, the coefficients of variation for serum progesterone were 66% and 75% with the vaginal and subcutaneous routes, respectively, indicating low variability, and 146% with the intramuscular route, indicating high variability. Two linear regression models were conducted: a normal linear regression model, which found no significant effect of administration route on serum progesterone, and a mixed-effects linear regression model, which also showed no statistically significant differences between routes. ConclusionAll routes of progesterone administration showed satisfactory day 5 mean serum progesterone levels, regardless of administration route.

O-110 Endometrial preparation for FET: HRT vs. Natural cycle

Abstract Frozen-thawed embryo transfer (FET) cycles have increased dramatically over the past decade, mainly due to the introduction of vitrification as a more efficient method of cryopreservation, and the increase of the freeze-all strategy in order to reduce the risk of OHSS. Planning of FET cycles is a key step for the implantation of the frozen-thawed embryos since it allows the synchronization of the endometrium with the developmental stage of the embryo. Endometrial preparation can be achieved either through hormonal replacement treatment (HRT) by an artificial cycle using exogenous estrogen administration for the development of the endometrium and subsequent administration of exogenous progesterone for its secretory transformation (AC-FET) or via a natural cycle, following the detection of LH surge (NC-FET), or the trigger of ovulation with human chorionic gonadotrophin (mNC-FET). The scope of the current presentation is to provide an overview of the different methods of endometrial preparation for FET cycles, their advantages, and disadvantages, and the evidence regarding clinical but also adverse obstetrical and perinatal outcomes, following each different protocol. Trial registration number

Effects of exogenous progesterone on the expression of mineral regulatory molecules by ovine endometrium and placentomes†.

This study aimed to determine whether the acceleration of conceptus development induced by the administration of exogenous progesterone (P4) during the preimplantation period of pregnancy alters calcium, phosphate, and vitamin D signaling at the maternal-conceptus interface. Suffolk ewes (n = 48) were mated to fertile rams and received daily intramuscular injections of either corn oil (CO) vehicle or 25mg of progesterone in CO (P4) for the first 8days of pregnancy and hysterectomized on either Day 9 (CO, n = 5; P4, n = 6), 12 (CO, n = 9; P4, n = 4) or 125 (CO, n = 14; P4, n = 10) of gestation. The expression of S100A12 (P < 0.05) and fibroblast growth factor receptor (FGFR2) (P < 0.01) messenger RNAs (mRNAs) was lower in endometria from P4-treated ewes on Day 12. The expression of ADAM10 (P < 0.05) mRNA was greater in endometria from P4-treated ewes on Day 125. The expression of ADAM10 (P < 0.01), FGFR2 (P < 0.05), solute carrier (SLC)20A1 (P < 0.05), TRPV5 (P < 0.05), and TRPV6 (P < 0.01) mRNAs was greater, but KL mRNA expression was lower (P < 0.05) in placentomes from P4-treated ewes at Day 125. There was lower endometrial and greater placentomal expression of mRNAs involved in mineral metabolism and transport in twin compared to singleton pregnancies. Further, the expression of mRNAs involved in mineral metabolism and transport was greater in P4-treated twin placentomes. KL, FGF23, vitamin D receptor (VDR), S100A9, S100A12, S100G, and CYP27B1 proteins were immunolocalized in endometria and placentomes. Exogenous P4 in early pregnancy altered the expression of regulators of calcium, phosphate, and vitamin D on Day 125 of pregnancy indicating a novel effect of P4 on mineral transport at the maternal-conceptus interface.

Route of administration of exogenous progesterone for luteal support does not significantly affect the serum concentration in assisted reproductive technology.

The objective of this research is to study the guiding role of serum progesterone level on exogenous luteal support protocols. In the retrospective study, a total of 537 infertile women undergoing IVF/ICSI were recruited. Serum samples were obtained for serum progesterone measurements. The results demonstrated that the progesterone levels of all women gradually decreased over the course of 7 days after ET. The progesterone level of the pregnant women reached a nadir on day 7 after ET and subsequently began to rise, while the progesterone level of the non-pregnant women continued to decrease. Even with different routes of administration of exogenous progesterone, the progesterone levels followed the same patterns. The serum progesterone level does not represent the adequacy of exogenous progesterone supplementation. Therefore, there is no need to measure serum progesterone levels frequently after embryo transfer or adjust the dose according to serum progesterone levels.

Prenatal exposure to exogenous progesterone adversely affects fetal development in Albino rats

BackgroundThe current study was carried out to investigate the effects of exogenous progesterone on fetal development in rats.ResultsPlacental weights did not vary in control and treated groups. Fetal weights were significantly reduced in the low- and high-dose progesterone groups. Fetal CVL was significantly reduced in both treatment groups compared to control group. In fetuses that received maternal treatment with low- and high-dose progesterone, several parts of the fetal skeleton showed incomplete ossification. Alkaline phosphatase was decreased in the bones of fetuses born to progesterone-treated dams. The testes and ovaries of the fetuses of the dams treated with low and high doses of progesterone showed degenerative seminiferous tubules and failed sex cord development into primordial follicles, respectively.ConclusionsThe administration of exogenous progesterone during pregnancy adversely influences fetal growth, skeletal construction, and sex organ development.

Exogenous progesterone for LH surge prevention is redundant in ovarian stimulation protocols

During ovarian stimulation for IVF–embryo transfer treatment, a premature LH surge may lead to progesterone elevation that disrupts endometrial maturation and affects the probability of pregnancy following fresh embryo transfer. Preventing this LH surge and progesterone elevation using gonadotrophin-releasing hormone (GnRH) analogues is considered a standard practice. The same policy applies to cycles in which the ‘freeze-all’ protocol has been selected from the outset (e.g. donors), but the need for this has not been discussed. Moreover, in ‘freeze-all’ cycles, exogenous progesterone administration tends to replace GnRH antagonists, without reducing efficacy after embryo transfer in frozen-thawed cycles. Nevertheless, as exogenous progesterone is expected to have the same impact on the endometrium as endogenous progesterone, it is clear that, unlike in fresh cycles, in ‘freeze-all’ cycles an endogenous LH surge prevention does not seem necessary. Therefore, both GnRH antagonists and exogenous progesterone appear to be redundant in ‘freeze-all’ cycles, and in this context the indications for the use of GnRH analogues in ovarian stimulation protocols need to be revisited.

Uterine Torsion Associated with Open Pyometra in a Bitch

Background: Pyometra or pyometritis is a serious and common condition of intact female dogs characterized by the inflammation of the uterus with a buildup of purulent exudate. It may be classified as open or closed. If untreated, pyometra can lead to uterine rupture and sepsis. Pyometra may also predispose to uterine torsion, defined as a rotation of one or both uterine horns around its longitudinal axis. Uterine torsion in female dogs is rare, and usually with late pregnancy or parturition. This case report describes the clinical presentation and therapeutic management of uterine torsion correlated with open pyometra in a non-gravid bitch with no history of exogenous progesterone exposure. Case: A 10-year-old intact Yorkshire Terrier bitch weighing 3.2 kg was referred to a veterinary clinic in Porto Alegre, Brazil, with a 7 day history of prostration, anorexia, polydipsia, and sanguinopurulent vulvar discharge. Physical examination revealed pronounced abdominal tenderness. On abdominal ultrasonography, the uterus was enlarged and filled with cellular anechoic content, suggestive of pyometra. A complete blood count showed mild microcytic normochromic anemia and leukocytosis. The animal was stabilized and an urgent ovariohysterectomy was performed. Preanesthetic analgesia consisted of subcutaneous methadone 0.3 mg/kg. Anesthesia was induced with propofol 3 mg/kg i.v. and maintained with inhaled isoflurane. During the procedure, significant enlargement of the left uterine horn and slight enlargement of the right uterine horn were observed. In addition, a torsion was identified near the left ovary, with copious sanguinopurulent secretion. The animal remained under observation and fluid therapy for 48 h after the procedure and was discharged to postoperative follow-up. After discharge, the following treatment was medicine, local cleaning and rest for 14 days. Concluding the therapeutic process with a satisfactory outcome. Discussion: Uterine torsion is considered rare in female dogs, and when it does occur, it is usually associated with late pregnancy or parturition. In this case, pregnancy was not a predisposing factor, but the animal had pyometra, which may have contributed to the torsion. Exogenous progesterone administration to inhibit the estrous cycle significantly increases the risk of pyometra; however, in the case reported herein, there was no history of progesterone therapy. The most likely cause was prolonged, repeated progesterone stimulation in the luteal phase, since the animal developed pyometra at the age of 10. Both uterine torsion and pyometra may progress to cause severe systemic complications. However, none was observed in the present case. Despite the high mortality rate, the animal survived, probably due to the open pyometra, which is associated with better prognosis than closed pyometra. Nevertheless, drainage was not enough to relieve enlargement of the uterus and ligaments, which may have facilitated torsion. Pyometritis associated with uterine torsion has rarely been reported in the literature, especially in small animals. Early diagnosis is key, as is surgical treatment via ovariohysterectomy. The surgical procedure had therapeutic purpose and was managed satisfactorily. The mechanism of uterine torsion has yet to be fully elucidated, which highlights the importance of this report. Additionally, it is rare in dogs, with very few reports in the non-gravid uterus.

Luteal Phase in Assisted Reproductive Technology.

Luteal phase (LP) is the period of time beginning shortly after ovulation and ending either with luteolysis, shortly before menstrual bleeding, or with the establishment of pregnancy. During the LP, the corpus luteum (CL) secretes progesterone and some other hormones that are essential to prepare the uterus for implantation and further development of the embryo, the function known as uterine receptivity. LP deficiency (LPD) can occur when the secretory activity of the CL is deficient, but also in cases of normal CL function, where it is caused by a defective endometrial response to normal levels of progesterone. LPD is particularly frequent in treatments using assisted reproductive technology (ART). Controlled ovarian stimulation usually aims to obtain the highest number possible of good-quality oocytes and requires the use of gonadotropin-releasing hormone (GnRH) analogs, to prevent premature ovulation, as well as an ovulation trigger to achieve timed final oocyte maturation. Altogether, these treatments suppress pituitary secretion of luteinizing hormone (LH), required for the formation and early activity of the CL. In addition to problems of endometrial receptivity for embryos, LPD also leads to dysfunction of the local uterine immune system, with an increased risk of embryo rejection, abnormally high uterine contractility, and restriction of uterine blood flow. There are two alternatives of LPD prevention: a direct administration of exogenous progesterone to restore the physiological progesterone serum concentration independently of the CL function, on the one hand, and treatments aimed to stimulate the CL activity so as to increase endogenous progesterone production, on the other hand. In case of pregnancy, some kind of LP support is often needed until the luteal–placental shift occurs. If LPD is caused by defective response of the endometrium and uterine immune cells to normal concentrations of progesterone, a still poorly defined condition, symptomatic treatments are the only available solution currently available.

FROZEN-THAWED EMBRYO TRANSFERS ARE ASSOCIATED WITH A HIGHER RISK OF LARGE FOR GESTATIONAL AGE NEWBORNS

Improvements in cryopreservation techniques associated with the possible impairment in endometrial receptivity due to the supra-physiologic hormonal levels observed during conventional controlled ovarian stimulation (COS) have increased the implementation of frozen-thawed embryo transfers (FET). Perinatal outcomes of fresh embryo transfers (ET) and FET have shown to be similar. However, several studies associate FET with a higher risk of large-for-gestational-age (LGA), thereby, increasing risk of adverse obstetric and neonatal outcomes. This study aims to assess whether FET is associated with a higher risk of large for gestational age newborns, compared with fresh ET in our population. Retrospective, single center study performed from 2017 to 2019. A total of 561 patients who became pregnant after fresh and frozen embryo transfers. A first study group included all IVF cycles where fresh embryo transfer resulted in a singleton live birth (fresh group n=254). A second cohort included FET that led to a singleton live birth (FET group n= 307). All embryos were transferred at a blastocyst stage and vitrification was the only cryopreservation method. In all FET the endometrium was artificially prepared through the administration of exogenous estrogen and progesterone. Data was collected from telephone surveys. We compared the number of LGA newborns and weight differences in both groups. z-test was applied for statistical analysis. A p value <0.05 was considered significant. The median gestational age in both groups was 38 weeks. The mean adjusted birth weight after FET group was higher by 109.26 g, than the fresh group (3269.32 g vs 3160.13 g respectively, p=0.285). The incidence of newborns that weighted ≥ p50 was significantly higher for FET group (142 vs 75 for FET and fresh respectively, p= 0.000048). Moreover, the incidence of LGA livebirths was significantly higher in the FET group (p=0.0226) (23 from the FET group vs 8 from fresh ET). No difference in female to male ratio for LGA newborns or preterm birth rate was identified between groups. FET is associated with increased risk of LGA in our population. FET has become an important technique in IVF; however, whether it should be the first choice for ET requires further analysis. An individual approach should remain when deciding between fresh or frozen embryo transfers. Longer-term potential health effects remain to be evaluated.

Effect of exogenous progesterone administration on smoking topography

IntroductionProgesterone has been implicated as protective against drug taking behaviors, including combustible cigarettes. While prior research indicates higher endogenous progesterone levels are associated with a reduction in smoking intensity (as measured by smoking topography), it is unknown if exogenous delivery of progesterone may have the same effect. MethodsThis double-blind, counterbalanced, cross-over randomized trial enrolled women between the ages of 18 and 40 who smoked at least five cigarettes per day and were currently using oral contraceptives. After overnight abstinence participants attended two topography lab sessions. One lab session was conducted during progesterone (200 mg twice per day) treatment and the other was during placebo treatment. Analyses included linear mixed effect models to examine the effect of exogenous progesterone administration and endogenous progesterone values on topography outcomes. ResultsParticipants (n = 43) were 23.8 (standard deviation [SD] ± 4.5) years old, smoked 10.5 (SD ± 3.7) cigarettes per day. Compared to placebo administration, progesterone administration reduced cumulative puff volume by 300 mL (95% confidence interval [CI]: −536, −65; p-value = 0.01) with additional trends indicating possible reductions in the number of puffs, average puff volume, and average flow. There were no significant effects of endogenous progesterone on smoking topography outcomes. ConclusionsProgesterone administration has the potential to reduce smoking intensity after overnight abstinence in women of reproductive age. Additional research is needed to explore how this may relate to smoking cessation outcomes in women of reproductive age.

Impact of Serum Estradiol Levels Prior to Progesterone Administration in Artificially Prepared Frozen Embryo Transfer Cycles.

Background: The need for endocrine monitoring in artificial cycles for frozen embryo transfer (FET) remains unclear and, more specifically, the value of the late-proliferative phase serum estradiol (E2) levels is with conflicting evidence in current literature.Objective: To investigate whether artificial FET cycles require endocrine monitoring for the serum E2 level prior to initiation of exogenous progesterone administration after an endometrial thickness of 6.5 mm has been reached.Design: One thousand two hundred and twenty-two (n = 1,222) artificial FETs performed in a tertiary center between 2010 and 2015 were subdivided into 3 groups according to the following late-proliferative serum E2 level percentiles: ≤p10 (E2 ≤144 pg/ml; n = 124), p11–p90 (E2 from 145 to 438 pg/ml; n = 977) and >p90 (E2 >439 pg/ml; n = 121).A mixed-effects multilevel multivariable regression analysis was performed to assess the potential effect of the late-proliferative E2 level on the live birth rate (LBR).Results: The level of late-proliferative circulating E2 showed no significant difference in terms of LBR after FET. Specifically, the multivariable regression model demonstrated a LBR of 19.5% for the p11–p90 reference group, compared to 24.4% for the ≤p10 (p = 0.251) and 19.5% for the >p90 group (p = 0.989).Conclusion: In this large retrospective dataset, no association was observed between late-proliferative phase serum E2 levels and LBR following FET in artificially prepared cycles. Although, caution is warranted due to the retrospective nature of the analysis and the potential for unmeasured confounding, we argue that monitoring of the late-proliferative serum E2 levels and using them to guide clinical decision-making (e.g., medication step-up, cycle prolongation or cancelation) may be of questionable value.

Effect of exogenous progesterone administration on cigarette smoking-related symptomology in oral contraceptive users who smoke

Cigarette smoking-related symptomatology (e.g., craving; SRS) is linked to relapse after a quit attempt. SRS varies by menstrual phase, possibly due to variations in sex hormones (e.g., progesterone), though much of the research to-date has relied on observations from the menstrual cycle acting as a proxy for hormone levels. The goal of this study was to examine the effect of exogenous progesterone on SRS during ad libitum smoking and following overnight abstinence.Oral contraceptive users who smoked completed two 9-day crossover testing periods (7 days of ad libitum smoking and 2 days following overnight abstinence) while taking double-blind active/placebo exogenous progesterone. Participants completed questionnaires to measure SRS. The effect of exogenous progesterone and endogenous hormones (progesterone, estradiol, and progesterone-to-estradiol [P/E2] ratio) on SRS was assessed with paired t-tests and linear mixed effect models.Participants (n = 53) were, on average, 24 years old and smoked 11 cigarettes per day. During ad libitum smoking, a doubling of the P/E2 ratio was associated with 0.09 points lower anticipated relief from negative affect (95% confidence interval [CI]: 0.03–0.15 points lower; p = 0.008) and 0.11 points lower psychological reward (95% CI: 0.03–0.18 points lower; p = 0.006). After correction for multiple testing, these associations were not statistically significant: anticipated relief from negative effect (p = 0.10) and psychological reward (p = 0.09). No other significant associations were observed.Although substantial previous literature indicates that progesterone influences SRS, exogenous progesterone administration did not alter SRS here. Additional research is needed to elucidate alternative mechanisms involved in menstrual phase effects on SRS.

Commentary on Tosun et al. (2019): Dynamic changes in sex hormones and smoking cessation.

There is growing evidence suggesting that exogenous progesterone may improve smoking cessation outcomes among women. We hypothesize that exogenous progesterone administration can result in stable progesterone levels, and that it is the absence of dynamic hormone change that may lead to improved smoking cessation outcomes.

Prevention of miscarriage following ovulation induction in women with endocrine infertility in anamnesis

Prescription of adjusted maintenance hormonal therapy during early stages of induced pregnancy is one of the most effective means of reducing reproductive losses.Aim. To improve the maintenance hormonal therapy during early stages of induced pregnancy in patients with endocrine infertility of various genesis in anamnesis.Materials and methods. In total, 44 women with induced singleton pregnancy and anovulatory infertility in anamnesis and 20 healthy pregnant women underwent ultrasound and hormonal monitoring during the first trimester of pregnancy. Depending on the dynamics of hormonal changes, corrective hormonal therapy was prescribed for patients with induced pregnancy. Prolongation of pregnancy up to 12 weeks was considered to be the main criterion for the evaluation of the therapeutic measures effectiveness. Statistical processing of data was performed using the programs StatSoft Statistica v.6.0, Microsoft Excel XP.Results. Despite the exogenous administration of progestins in the group of women with anovulatory infertility in anamnesis, there were detected high risks of miscarriage (47.7 %), chorionic pathology (29.5 %), abortions (27.3 %). Hormonal monitoring in patients with termination of pregnancy and hypothalamic-pituitary insufficiency revealed an initially low level of β-hCG, normal level of progesterone but an inadequate their rise in dynamics; in patients with hyperprolactinemia – a very high concentration of progesterone, normal β-hCG level in early gestation and its gradual decrease during the first trimester; in patients with hyperandrogenemia – a very high concentration of progesterone at the beginning and progressive its decrease during the first trimester, inadequate rise of β-hCG from the beginning of the study combined with increased levels of androgens – dehydroepiandrostenediol sulfate and/or free testosterone.Conclusions. In order to select an appropriate maintenance hormonal therapy, the concentration of progesterone and β-hCG should be determined at the beginning of the first trimester in patients with induced pregnancy and endocrine infertility in anamnesis. The first weeks of gestation (hyperconcentration of hormones) and the middle of the first trimester (corpus luteum regression) are the critical periods for such pregnant women. An adequate rise of β-hCG with normal or increased level of progesterone in women with hyperandrogenism and hyperprolactinemia during the first weeks of pregnancy serves as a reason for withdrawal of exogenous progesterone administration with a possible prolonged therapy after 6–7 weeks of gestation under the dynamic control of progesterone and β-hCG levels. Patients with hypothalamic-pituitary insufficiency should receive constant maintenance hormonal therapy with progestins in high therapeutic doses at the beginning of pregnancy.