Progesterone Supplementation Research Articles

US Doppler in the monitoring of hemodynamic alterations of the supplementary corpus luteum in cyclic mares

For the success of an equine breeding program, follow-up by a veterinarian is essential. In early pregnancy, luteinized follicles develop into an accessory or supplementary corpus luteum (SCL) which, like the primary corpus luteum, produces progesterone and contributes to the maintenance of early pregnancy (Hannan et al. Domestic Animal Endocrinology. 2020; 72:106424). If SCLs are insufficient, progesterone supplementation may be required but research data in this field are limited. Hence it is important to monitor the hemodynamic changes of the SCLs using Doppler ultrasonography (US Doppler). The aim of this study was to follow the onset and development of SCLs, evaluate their degrees of vascularization, subjectively (determining vascularity) and objectively (comparing the number and intensity of pixels). Crossbred mares (n=15) were inseminated, then SCLs monitored in Rio de Janeiro, Brazil. There was an average of 2.8 SCL/mare due to the ovulation and development of SCLs and differences in vascular perfusionwere seen between days 35 and 70 of gestation. There was a correlation (P<0.001) between SCL vascularization and the number and intensity of pixels, with the greatest increase occurring between days 70 and 119 of pregnancy. This corresponds with the peak production of progesterone by these structures. From day 120, a decrease in the vascular perfusion of the SCLs was seen, and at 140 days of gestation, the few SCLs that remained were in regression. This is logical because by this stage of gestation, progesterone is mainly of placental origin. Thus, US Doppler evaluation of SCLs in early pregnancy may assist in the decision whether to administer supplementary progesterone and for how long or not at all. Future research that may evaluate the contribution of equine chorionic gonadotropin to the formation of SCLs, its effect on the plasma concentration of progesterone as well as any requirement for progesterone supplementation at all is required.

Progesterone and Androstenedione Are Important Follicular Fluid Factors Regulating Porcine Oocyte Maturation Quality.

Oocytes matured in vitro are useful for assisted human and farm animal reproduction. However, the quality of in vitro matured oocytes is usually lower than that of in vivo matured oocytes, possibly due to the absence of some important signal regulators in vitro. In this study, untargeted metabolomics was used to detect the changes in the metabolites in the follicular fluid (FF) during in vivo pig oocyte maturation and in the culture medium during in vitro maturation. Our results showed that the total metabolite changing profile of the in vivo FF was different from that of the in vitro maturation medium, but the levels of 23 differentially expressed metabolites (DEMs) changed by following the same trend during both in vivo and in vitro pig oocyte maturation. These 23 metabolites may be important regulators of porcine oocyte maturation. We found that progesterone and androstenedione, two factors in the ovarian steroidogenesis pathway enriched from the DEMs, were upregulated in the FF during in vivo pig oocyte maturation. The levels of these two factors were 31 and 20 fold, respectively, and they were higher in the FF than in the culture medium at the oocyte mature stage. The supplementation of progesterone and androstenedione during in vitro maturation significantly improved the pig oocyte maturation rate and subsequent embryo developmental competence. Our finding suggests that a metabolic abnormality during in vitro pig oocyte maturation affects the quality of the matured oocytes. This study identified some important metabolites that regulate oocyte maturation and their developmental potential, which will be helpful to improve assisted animal and human reproduction.

Estrogen modulation of cortical spreading depression

Background and aimsCortical spreading depression (CSD), a transient neuronal and glial depolarization that propagates slowly across the cerebral cortex, is the putative electrophysiological event underlying migraine aura and a headache trigger. Migraine is three times more prevalent in women than men, linked to circulating female hormones. High estrogen levels or estrogen withdrawal may be a migraine trigger for many women. We, therefore, aimed to examine whether sex, gonadectomy, and female hormone supplementation and withdrawal affect the susceptibility to CSD.MethodsTo determine CSD susceptibility, we recorded the frequency of CSDs triggered during 2-h topical KCl application in intact or gonadectomized female and male rats, without or with estradiol or progesterone supplementation via daily intraperitoneal injections. Estrogen or progesterone treatment followed by withdrawal was studied in a separate cohort. To take the first step towards identifying potential mechanisms, we studied glutamate and GABAA receptor binding using autoradiography.ResultsThe CSD frequency in intact female rats was higher than intact male and ovariectomized rats. We did not detect a change in CSD frequency during different stages of the estrous cycle in intact females. Daily estrogen injections for three weeks did not change CSD frequency. However, one-week estrogen withdrawal after two weeks of treatment significantly increased CSD frequency compared with the vehicle group in gonadectomized females. The same protocol of estrogen treatment and withdrawal was ineffective in gonadectomized males. In contrast to estrogen, daily progesterone injections for three weeks elevated CSD susceptibility, and one-week withdrawal after two weeks of treatment partially normalized this effect. Autoradiography did not reveal significant changes in glutamate or GABAA receptor binding density after estrogen treatment and withdrawal.ConclusionsThese data suggest that females are more susceptible to CSD, and sexual dimorphism is abrogated by gonadectomy. Moreover, estrogen withdrawal after prolonged daily treatment enhances CSD susceptibility. These findings may have implications for estrogen-withdrawal migraine, although the latter tends to be without aura.

The association between the type of progesterone supplementation and miscarriage risk in women who have had a positive pregnancy test following embryo transfer: a retrospective cohort study.

The purpose of this study was to identify if switching from intramuscular (IM) to vaginal progesterone compared to staying on IM progesterone after a positive pregnancy test following embryo transfer (ET) is associated with miscarriage risk. A retrospective cohort study was performed in a private university-affiliated fertility clinic and included women aged 18-50years with a positive pregnancy test following ET. The two groups studied were: women who stayed on IM progesterone following a positive pregnancy test and those who switched to vaginal progesterone after a positive test. The main outcome measured was risk of miscarriage < 24weeks gestation as a proportion of non-biochemical pregnancies. 1988 women were included in the analysis. Among the baseline characteristics, the presence of prior miscarriages as well as prior failed ETs, and frozen cycles (vs fresh) as type of transfer were associated with IM progesterone use (p values ≤ 0.01). As per miscarriage risk < 24weeks, 22.4% (274/1221) of patients in the IM progesterone group experienced a miscarriage compared with 20.7% (159/767) in the vaginal progesterone group (OR 0.90; 95% CI 0.73-1.13). A multivariable logistic regression model revealed an adjusted OR (aOR) of 0.97 (95% CI 0.77-1.22). This study suggests that switching from IM to vaginal progesterone after a positive pregnancy test following an ET is not associated with miscarriage risk. Considering that IM progesterone imposes substantial discomfort, this study offers reassurance and some flexibility in treatment protocols. Further prospective studies are necessary to corroborate the results of this study.

Ovarian and Energy Status in Lame Dairy Cows at Puerperium and Their Responsiveness in Protocols for the Synchronization of Ovulation.

The purpose of this study was to assess the ovarian and energy status of multiparous lame dairy cows at the end of puerperium and investigate their responsiveness to estrous synchronization treatment regimens. Initial lameness scoring was performed at 28 ± 5 and 37 ± 5 d post partum, followed by lesion documentation and treatment. Cows were blocked by lameness severity and were randomly allocated to an estrous synchronization treatment regimen with seven days of progesterone supplementation (group LP, n = 26) or with an administration of PGF2α twice, 14 d apart (group LC, n = 26). Non-lame cows served as controls (group C, n = 27) and the same treatment regimen was imposed as that for group LC. Twelve days after estrous presynchronization, an Ovsynch treatment regimen and timed AI were imposed. Ultrasonography of the ovaries and blood sampling for progesterone were used to assess cyclicity status, whereas β-hydroxybutyrate (BHBA) and non-esterified fatty acids (NEFA) were used to assess energy status. Lame cows were to a greater proportion non-cycling (36.5% vs. 11.1%; p = 0.02), had greater overall NEFA concentrations (0.32 ± 0.02 vs. 0.26 ± 0.02 mEq/L; p = 0.02) and a greater incidence of elevated NEFA concentrations (53.9% vs. 29.6%, p = 0.04) compared to control cows. However, no interaction between energy and lameness status was evident regarding non-cycling cows. The percentage of cows responding to the presynchronization, synchronization and ovulating did not differ between groups LP, LC, and C. The first-service conception rate (FSCR) tended to be greater for group C (37.0%) compared to group LP (16.0%; p = 0.08). Long-term reproductive performance did not differ between lame and control cows, although culling rates did (21.2% vs. 0%, respectivly; p = 0.01). The severity of lameness had an effect on culling rates (30.6% vs. 0% for cows with marked vs. moderate lameness; p = 0.01), whereas the type of lesion largely explained poor reproductive performance (FSCR 13.9% vs. 40.0% for cows with claw horn disruptions vs. infectious lesions; p = 0.04). Conclusively, cows that were lame during puerperium are at a greater risk of not cycling irrespective of energy status. Treatment regimens for the synchronization of ovulation seem to be efficient at resuming ovarian cyclicity. Marked lameness was detrimental to survivability, whereas cows with claw horn lesions had compromised reproductive capacity.

Progesterone After Cerclage Does Not Improve the Preterm Birth Rate [ID: 1372160

INTRODUCTION: Preterm birth represents a leading cause of neonatal morbidity and mortality. Cerclage and progesterone supplementation are the two most frequently employed interventions to reduce the risk of prematurity. Guidelines for cerclage and progesterone have evolved as conflicting evidence for their use mounts, and combination therapy remains poorly understood. Our objective is to determine whether there is benefit to adjunct progesterone supplementation after cerclage placement. METHODS: This is a retrospective cohort review of all individuals who underwent transvaginal cerclage placement at a tertiary medical center between 2005 and 2021. The rate of delivery prior to 37 weeks was compared between participants with and without progesterone supplementation after cerclage. Several secondary maternal and neonatal outcomes were evaluated. Multivariate regression analysis accounted for cerclage indication, use of progesterone prior to cerclage, and other factors that affect prematurity risk. RESULTS: Of 451 participants, there were 160 history-indicated, 134 ultrasound-indicated, and 157 examination-indicated cerclages. Overall, 285 (63.2%) received postcerclage progesterone. Progesterone after cerclage did not decrease the rate of preterm delivery (adjusted odds ratio 1.1, 95% CI 0.4–2.6) for any indication of cerclage. Moreover, adjunct progesterone was associated with decreased latency between cerclage placement and delivery (P=&lt;.01). CONCLUSION: Prescribing patterns for progesterone after cerclage suggest clinical equipoise. We have found that adjunct progesterone does not decrease the preterm delivery rate and may in fact cause harm by decreasing latency from cerclage to delivery. These data do not support the use of progesterone after cerclage for any indication.

B-cell lymphoma 6 expression significantly differs by the uterine preparation method used for frozen embryo transfer

To determine whether B-cell lymphoma 6 (BCL6), an endometriosis-associated marker postulated to predict poor pregnancy outcomes, is differentially expressed in the window of implantation with various uterine preparation regimens commonly used for frozen embryo transfers. A retrospective cohort study. An academic center. Patients with infertility who underwent endometrial biopsy for BCL6 evaluation INTERVENTION(S): Exogenous estradiol and/or progesterone. Endometrial BCL6 histological score (HSCORE) and overexpression (HSCORE >1.4) RESULT(S): Two hundred and forty-four patients were included in the analysis: 76 patients were sampled in a natural menstrual cycle without exogenous hormone exposure (NC), 25 under a modified natural cycle embryo transfer protocol with choriogonadotropin alfa injection followed by luteal phase vaginal progesterone supplementation (mNC), and 143 under a programmed cycle embryo transfer protocol, with estradiol administration followed by addition of intramuscular progesterone-in-oil injections (PC). Median HSCORE (interquartile range) was the highest in NC (3.0 [1.8-3.6]). BCL6 expression was significantly lower in mNC (1.1 [0.4-2.1]) and PC groups (0.8 [0.3-1.3]) compared with NC. In addition, BCL6 overexpression (HSCORE >1.4) was observed in 80.3% of NC, 40.0 % of mNC, and 23.1 % of PC. After adjusting for covariates, the endometrium exposed to exogenous progesterone had significantly lower odds of BCL6 overexpression than that of a natural menstrual cycle (adjusted odds ratio, 0.12 [95% CI 0.04-0.35] for mNC; and odds ratio, 0.08 [95% CI 0.04-0.17] for PC). BCL6 expression differs by the type of uterine preparation method, with lower levels observed with exogenous progesterone exposure. The validity and utility of BCL6 testing under medicated endometrial state warrants further investigation.

Role of intramuscular progesterone supplementation on the day of embryo transfer in artificial frozen cycles

BackgroundSufficient endometrial preparation with or without progesterone supplementation is crucial in artificial cycles with frozen embryo transfer (FET). We aimed to study the effect of intramuscular progesterone supplementation on the day of embryo transfer (ET) in artificial frozen cycles.MethodsA clinical cohort study involved women undergoing FET with artificially prepared endometrium. Serum progesterone levels were assessed on the day of ET. Accordingly, we recruited 177 women with progesterone levels more than 9.2 ng/ml in group 1, and 177 other women with progesterone levels less than 9.2 ng/ml in group 2. Women in group 1 received only 400 mg vaginal progesterone twice-daily after ET, while women in group 2 received additional intramuscular progesterone supplementation. The chemical, clinical, and ongoing pregnancy rates, as well as the pregnancy loss rate, were assessed in both groups.ResultsExpectantly, both groups showed a significant difference regarding the serum progesterone level on the day of ET (13.43 ± 4.65 vs 4.62 ± 2.77, P = 574). However, with additional intramuscular progesterone supplementation in group 2, both groups showed no significant difference regarding the chemical pregnancy rate (68.93% in group 1 vs 63.84% in group 2, P = 0.311), the clinical pregnancy rate (61.02% in group 1 vs 58.76% in group 2, P = 0.664), ongoing pregnancy rate (56.50% in group 1 vs 53.11% in group 2, P = 0.522), and pregnancy loss rate (7.41% in group 1 vs 9.62% in group 2, P = 0.564).ConclusionsIntramuscular progesterone supplementation in women with decreased serum progesterone levels could improve pregnancy outcomes in artificial frozen cycles.Trial registrationIt was first registered at ClinicalTrials.gov on 8/4/2021 with registration number NCT04837768.

The effect of maternal obesity and lipid profile on first-trimester serum progesterone levels

Prepregnancy overweight increases the risk of adverse perinatal outcomes. Maternal lipid profile plays a key role in the production of pregnancy hormones. The influence that obesity has on the specific mechanisms that may be involved and the potential associations with abnormal conditions in pregnancy are still poorly understood. This study aimed to evaluate the effect of maternal body mass index and lipid profile on first-trimester serum progesterone levels. This was a prospective cohort study including 734 pregnant people. First-trimester maternal serum progesterone, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured between 9 and 11 weeks' gestation. Free β-hCG, PAPP-A, age, body mass index, smoking status, gestational age at delivery, fetal sex, and birthweight were also recorded. Pregnant people were classified according to their body mass index into underweight (n=21), normal weight (n=395), overweight (n=221), obesity class I (n=64), and obesity class II/III (n=33) groups. Gestational age at sampling was 10.0 4±1.12 weeks. Serum progesterone levels decreased as maternal body mass index increased (35.84±12.00 ng/mL, 33.08±11.27 ng/mL, 28.04±8.91 ng/mL, 24.37±8.56 ng/mL, and 19.87±11.00 mL for underweight, normal weight, overweight, obesity class I, and obesity class II/III groups, respectively; P<.000001). There were statistically significant negative correlations between maternal progesterone and body mass index, triglycerides, and cholesterol/high-density lipoprotein cholesterol ratio, and positive correlations with gestational age at sampling, maternal age, cholesterol, high-density lipoprotein cholesterol, crown-rump length, free β-hCG, and PAPP-A. Linear regression showed that the only independent predictor variables for progesterone levels were body mass index (P<.0001), PAPP-A (P<.0001), high-density lipoprotein cholesterol (P<.0001), and free β-hCG (P<.0001) (R2=0.33; P<.0000001). First-trimester serum progesterone levels were lower in overweight pregnant people and markedly decreased in those with obesity, especially obesity class II/III. Maternal high-density lipoprotein cholesterol was independently related to progesterone levels as a protective factor. Benefits of progesterone supplementation in pregnant people with obesity need further evaluation.

Progestin-related breast volume changes in a woman with complete androgen insensitivity syndrome (CAIS).

A 31-year-old woman with complete androgen insensitivity syndrome (CAIS) experienced breast volume fluctuations during biphasic hormone replacement therapy consisting of estradiol and cyclical dydrogesterone, a progestin. 3D breast volume measurements showed a 100 cc volume (17%) difference between estradiol monotherapy and combined estradiol and dydrogesterone treatment. Progestogen-dependent breast volume changes have not been reported in the literature. Our findings suggest a correlation between progestogen use and breast volume. Due to the rapid cyclical changes, we hypothesize that the effect is caused by fluid retention. There is limited reports available on the effects of progesterone on breast development and volume. 3D imaging provides an easy-to-use method to quantify breast volume. The patient in our case description clearly showed that cyclic progesterone use might induce substantial cyclic changes in breast volume. In women with complete androgen insensitivity syndrome (CAIS), monotherapy with estrogen or continuous supplementation of progesterone might be preferable over cyclic progesterone use.

Progesterone and Its Metabolites Play a Beneficial Role in Affect Regulation in the Female Brain.

Premenstrual dysphoric disorder is a female affective disorder that is defined by mood symptoms. The condition is linked to unstable progesterone concentrations. Progestin supplementation is given in cases of threatened or recurrent miscarriage and for luteal phase support. Progesterone is essential for implantation, immune tolerance, and modulation of uterine contractility. For a long time, the administration of progestins was associated with an unfavorable impact on mood, leading to negative affect, and, therefore, was contraindicated in existing mood disorders. Establishing the role of the natural progesterone derivative allopregnanolone in advances in the treatment of postpartum depression has shed new light on the general pathophysiology of mood disorders. Allopregnanolone directly interacts with gamma-aminobutyric acid type A (GABA-A) receptors even at nanomolar concentrations and induces significant anti-depressant, anti-stress, sedative, and anxiolytic effects. Postpartum depression is caused by a rapid drop in hormones and can be instantly reversed by the administration of allopregnanolone. Premenstrual dysphoric disorder can also be considered to result from insufficient neuroactive steroid action due to low progesterone derivative concentration, unstable hormone levels, or decreased receptor sensitivity. The decrease in progesterone levels in perimenopause is also associated with affective symptoms and an exacerbation of some psychosomatic syndromes. Bioidentical progesterone supplementation encounters several obstacles, including limited absorption, first-pass effect, and rapid metabolism. Hence, non-bioidentical progestins with better bioavailability were widely applied. The paradoxical, unfavorable effect of progestins on mood can be explained by the fact that progestins suppress ovulation and disturb the endocrine function of the ovary in the luteal phase. Moreover, their distinct chemical structure prevents their metabolism to neuroactive, mood-improving derivatives. A new understanding of progesterone-related mood disorders can translate the study results from case series and observational studies to cohort studies, clinical trials, and novel, effective treatment protocols being developed.

Management of Pregnancy with Cervical Shortening: Real-Life Clinical Challenges.

Background and Objectives: Preterm birth is the leading cause of neonatal mortality worldwide and may be responsible for lifelong morbidities in the survivors. Cervical shortening is one of the common pathways to preterm birth associated with its own diagnostic and management challenges. The preventive modalities that have been tested include progesterone supplementation and cervical cerclage and pessaries. The study aimed to assess the management strategies and outcomes in a group of patients with a short cervix during pregnancy or cervical insufficiency. Materials and Methods: Seventy patients from the Riga Maternity Hospital in Riga, Latvia, were included in the prospective longitudinal cohort study between 2017 and 2021. Patients were treated with progesterone, cerclage, and/or pessaries. The signs of intra-amniotic infection/inflammation were assessed, and antibacterial therapy was given when the signs were positive. Results: The rates of PTB were 43.6% (n = 17), 45.5% (n = 5), 61.1% (n = 11), and 50.0% (n = 1) in progesterone only, cerclage, pessary, and cerclage plus pesssary groups, respectively. The progesterone therapy was associated with a reduced preterm birth risk (x2(1) = 6.937, p = 0.008)), whereas positive signs of intra-amniotic infection/inflammation significantly predicted the risk of preterm birth (p = 0.005, OR = 3.82, 95% [CI 1.31-11.11]). Conclusions: A short cervix and bulging membranes, both indicators of intra-amniotic infection/inflammation, are the key risk factors in preterm birth risk predictions. Progesterone supplementation should remain at the forefront of preterm birth prevention. Among patients with a short cervix and especially complex anamnesis, the preterm rates remain high. The successful management of patients with cervical shortening lies between the consensus-based approach for screening, follow-up, and treatment on the one side and personalising medical therapy on the other.

Influence of delayed blastulation and expansion grade on clinical outcomes of high-quality blastocyst transfer: an analysis of 1751 frozen-thawed cycles

The aim of the study was to compare retrospectively the extent of blastulation timing (Day 5 or later) and expansion grade to predict the ability of blastocysts to give rise to a pregnancy. Blastocysts frozen on day 5 with a lower expansion grade (group D5) or day 6 with a higher expansion grade (group D6) were included. A single embryo was thawed and transferred on day 5 after ovulation or progesterone supplementation. Differences in patient baseline characteristics, endometrial preparation and pregnancy outcomes between groups were stratified by patient age and anti-Müllerian hormone (AMH) levels. Logistic regression was used to analyse the results. A total of 617 blastocysts in group D5 and 1134 blastocysts in group D6 were assessed. Stratified analyses showed higher biochemical pregnancy, clinical pregnancy and live birth rates for patients aged less than 30 years old, and higher ongoing pregnancy rate for patients with AMH ≥ 1.1 ng/ml. For patients aged less than 30 years old, the biochemical pregnancy, clinical pregnancy and live birth rates in group D5 were higher than those in group D6.

A Paternal Fish Oil Diet Preconception Reduces Lung Inflammation in a Toxicant-Driven Murine Model of New Bronchopulmonary Dysplasia.

New bronchopulmonary dysplasia (BPD) is a neonatal disease that is theorized to begin in utero and manifests as reduced alveolarization due to inflammation of the lung. Risk factors for new BPD in human infants include intrauterine growth restriction (IUGR), premature birth (PTB) and formula feeding. Using a mouse model, our group recently reported that a paternal history of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure increased his offspring's risk of IUGR, PTB, and new BPD. Additionally, formula supplementation of these neonates worsened the severity of pulmonary disease. In a separate study, we reported that a paternal preconception fish oil diet prevented TCDD-driven IUGR and PTB. Not surprisingly, eliminating these two major risk factors for new BPD also significantly reduced development of neonatal lung disease. However, this prior study did not examine the potential mechanism for fish oil's protective effect. Herein, we sought to determine whether a paternal preconception fish oil diet attenuated toxicant-associated lung inflammation, which is an important contributor to the pathogenesis of new BPD. Compared to offspring of standard diet TCDD-exposed males, offspring of TCDD-exposed males provided a fish oil diet prior to conception exhibited a significant reduction in pulmonary expression of multiple pro-inflammatory mediators (Tlr4, Cxcr2, Il-1 alpha). Additionally, neonatal lungs of pups born to fish oil treated fathers exhibited minimal hemorrhaging or edema. Currently, prevention of BPD is largely focused on maternal strategies to improve health (e.g., smoking cessation) or reduce risk of PTB (e.g., progesterone supplementation). Our studies in mice support a role for also targeting paternal factors to improve pregnancy outcomes and child health.

Effect of a progesterone-releasing intravaginal device (PRID) for 8 days during a modified Ovsynch protocol on pregnancy outcomes in lactating Holstein cows

Our objective was to evaluate the effect of a progesterone-releasing intravaginal device (PRID) in a 7-d Ovsynch protocol on pregnancy per artificial insemination (P/AI) and pregnancy loss, compared with a standard 7-d Ovsynch protocol without progesterone supplementation. We hypothesized that progesterone supplementation during an Ovsynch protocol would increase P/AI and decrease pregnancy loss. Data were collected on lactating Holstein cows (n = 716) that either received a 7-d Ovsynch protocol (control: d 0, 100 µg of GnRH; d 7, 500 µg of cloprostenol; d 9, µg of GnRH; n = 360) or a modified Ovsynch protocol with addition of a PRID (PRIDsynch; d 0, 100 µg of GnRH + PRID; d 7, 25 mg of dinoprost; d 8, PRID removal; d 9, 100 µg of GnRH; n = 356). All cows received timed artificial insemination (TAI) approximately 16 h after the second GnRH treatment. Pregnancy diagnosis was performed via ultrasonography on d 38 ± 3 after TAI and rechecked on d 80 ± 7 after TAI. Reproductive performance differed between treatments, with PRIDsynch cows having greater (38.9%) P/AI compared with control cows (31.7%) at d 38 ± 3 and also at d 80 ± 7 (34.6% vs. 28.9%, for PRIDsynch and control cows, respectively). Pregnancy loss did not differ among treatments.

Prevention of Pregnancy Loss: Combining Progestogen Treatment and Psychological Support

Pregnancy loss can be defined as a loss before either 20 or 24 weeks of gestation (based on the first day of the last menstrual period) or the loss of an embryo or fetus less than 400 g in weight if the gestation age is unknown. Approximately 23 million pregnancy losses occur worldwide every year, equating to 15-20% of all clinically recognized pregnancies. A pregnancy loss is usually associated with physical consequences, such as early pregnancy bleeding ranging in severity from spotting to hemorrhage. However, it can also be associated with profound psychological distress, which can be felt by both partners and may include feelings of denial, shock, anxiety, depression, post-traumatic stress disorder, and suicide. Progesterone plays a key part in the maintenance of a pregnancy, and progesterone supplementation has been assessed as a preventative measure in patients at increased risk of experiencing a pregnancy loss. The primary objective of this piece is to assess the evidence for various progestogen formulations in the treatment of threatened and recurrent pregnancy loss, postulating that an optimal treatment plan would preferably include a validated psychological support tool as an adjunct to appropriate pharmacological treatment.

Hormonal and Metabolic Factors Influence the Action of Progesterone on the Endometrium of Women with Polycystic Ovary Syndrome.

Hormonal and metabolic factors may influence endometrial quality and interfere with the action of progesterone. Therefore, the aim of our study was to address this issue. Participants were recruited from an outpatient reproductive endocrinology clinic at an academic tertiary medical care centre. All subjects underwent endometrial biopsy (EB) in the follicular phase of the cycle prior to treatment. Thereafter, they were treated with micronized progesterone (400 mg/day × 10 days intravaginally) from days 14-28 of the next cycle. A second EB was performed between days 21-24 of the cycle (the second phase). The metabolic and hormonal serum levels were evaluated during the implantation window. EB samples were analysed using light microscopy for histomorphometric analysis. The endometrium of women with Polycystic Ovarian Syndrome (PCOS) in the second phase demonstrated a uniform surface epithelium with less leukocyte infiltration and an absence of apoptotic figures compared to the control group. (p < 0.021). The thickness of the surface epithelium in the second phase of the PCOS group correlated positively with free and bioavailable testosterone values. The number of stromal cells increases with increasing insulin levels. Our results suggest that histomorphometric abnormalities of the endometrium persist and are linked to androgen and insulin levels despite progesterone supplementation in PCOS.

Cervical funneling is more predictive of preterm birth than cervical length alone in nulliparous women

Universal mid-trimester cervical length (CL) screening is a well-accepted practice for detection of women at risk of spontaneous preterm birth (sPTB). In those identified with a short cervix, progesterone supplementation is recommended. However, current guidelines do not consider a short cervix an indication for cerclage without a history of sPTB as it has poor sensitivity for this outcome. It is currently unclear if other sonographic features such as cervical funneling can identify a higher sPTB risk in a population without prior sPTB. This was a secondary analysis of the nuMom2b study, which enrolled a large prospective observational cohort of pregnant nulliparous women. Patients were stratified based on CL < 25mm or ≥25mm and presence or absence of funneling at the time of cervical length evaluation between 16-22 weeks’ gestation. Logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for sPTB adjusting for confounders. A Kaplan-Meier survival analysis was performed between groups and gestational age at delivery. 7,648 nulliparous women were included in the analysis. There were 169 (2.2%) women identified with a short CL < 25 mm and 52 (0.7%) with funneling. While a short CL had a higher risk of PTB (Table 1), a short CL was detected in only 24 (7.1%) of women who ultimately had a sPTB. The presence of a funnel was independently associated with higher odds of sPTB (OR 3.4, CI 1.9-8.1) when compared to CL < 25mm (OR 2.7, CI 1.7-4.4). On survival analysis, a short CL with funneling showed the lowest mean gestational age at delivery (Figure 2, p< .001). In a nulliparous population without prior sPTB, transvaginal cervical length alone is a poor predictor of preterm delivery, but presence of funneling significantly increases risk. This may identify a population of women who would benefit from cerclage.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Progesterone levels on the day of embryo transfer using a single pessary of 400mg of vaginal progesterone vs. 200mg x2 pessaries in hormonal replacement cycles.

Does the use of 400mg pessaries of micronized progesterone provide comparable results as pessaries of 200mg x2, in terms of progesterone levels in hormonal replacement cycles for embryo transfer?. Retrospective cohort study based on 299 embryo transfer treatments under artificial endometrial preparation carried out at Instituto Bernabeu. 131 patients received 1 pessary of 400 mg b.i.d. (group A) and 168 received 2 pessaries of 200 mg b.i.d. (group B). Mean serum progesterone levels were similar between groups (A: 13.64±4.47ng/mL vs. B: 13.88±7.17ng/mL). There were no differences in suboptimal progesterone levels between groups (A: 11.5% vs. B: 16.8%). In terms of patients receiving additional progesterone supplementation, there were no differences between groups (A: 26% vs. B: 35.3%.). No differences between groups were observed in clinical outcomes: pregnancy rate (PR) (A: 55% vs. B: 54.8%), biochemical pregnancy loss rate (BPLR) (A: 13.4% vs. B: 17.6%), miscarriage rate (MR) (A: 17.9% vs. B: 19.8%) and ongoing pregnancy rate (OPR) (A: 36.5% vs. B: 34.1%). One progesterone pessary of 400mg (Cyclogest®) twice daily appears to be non-inferior to the use of two-200mg pessaries twice daily in terms of progesterone levels in HRT cycles.

Index pregnancy placental histology and response to progesterone supplementation for prevention of recurrent preterm birth

Index pregnancy placental histology and response to progesterone supplementation for prevention of recurrent preterm birth