Progesterone In Early Pregnancy Research Articles

P-449 Association of corpus luteum activity in early pregnancy and live birth after assisted reproductive technology (ART) and intrauterine insemination (IUI)

Abstract Study question What is the incidence of low corpus luteum activity in early pregnancy, and how are endogenous progesterone levels and live birth achievement associated? Summary answer Frequently occurring low corpus luteum activity (progesterone-level) in early pregnancy after ART and IUI strongly predicts pregnancy demise, though not independent of trophoblast activity (hCG-level). What is known already Ovarian stimulation and human chorion gonadotropine (hCG) administration may induce a luteal phase defect via negative feedback on the hypothalamic-pituitary-ovarian (HPO) axis. Luteal phase support (LPS) is routinely administered with bio-identical progesterone or oral dydrogesterone (DYD). DYD has high oral availability, minimal interaction with the pituitary gland, and no cross-reactivity in enzyme-linked immunosorbent assay (ELISA) with progesterone. Therefore, utilizing DYD as LPS in IVF/ICSI or ovulatory IUI cycles provides a unique perspective to assess endocrine luteal activity. While various studies explored progesterone and hCG post-IVF or IUI, none focused solely on the corpus luteum’s sole endocrine function and its outcomes. Study design, size, duration This single-center, retrospective study (with institutional review board approval) investigated hCG and progesterone serum levels after IVF/ICSI cycles or IUI cycles supported with DYD as the sole LPS. The study aims to assess their predictive value, individually and in combination, for sustaining pregnancy. Data from 189 IVF/ICSI and 198 IUI early pregnancies, respectively, with positive hCG test between January 2017 and June 2022, was extracted from the patient management system at the University Fertility Center. Participants/materials, setting, methods Included were only first IVF/ICSI and IUI treatment-cycles with serum hCG value ≥ limit of detection (0.6 IU/l) between days 9 and 16 after fresh embryo transfer or IUI, respectively. Additionally to hCG, endogenous progesterone was determined and the relationship between these and pregnancy maintenance was investigated using logistic regression analysis. Inclusion criteria encompassed hCG-triggered cycles using DYD as the sole LPS, administered at 30 and 20 mg daily for IVF/ICSI and IUI therapy, respectively. Main results and the role of chance The 10th, 25th, 50th and 75th quantiles of serum progesterone are at 0.28, 3.75, 33.0 and 98.7 µg/l in IVF/ICSI cycles and 0.48, 2.70, 18.40 and 26.6 µg/l in IUI cycles. Women in the first quartile of progesterone levels had nearly exclusively pregnancy demise: live birth rate 3/47 (7%, 95% confidence interval (CI) 1-19%) and 0/47 (0%, 95% CI 0-7.5%) in IVF/ICSI and IUI cycles, respectively. In both IVF/ICSI and IUI, progesterone and hCG were highly correlated (correlation coefficient 0.83 in both cases). Accordingly, the association of serum hCG levels with live birth achievement was similar in quartile analyses. Using receiver operating characteristic (ROC) curves and Youden’s indices, the optimal cut-off values for predicting live birth were determined as follows: 16.49 µg/l (89 % sensitivity (SN) and 59 % specificity (SP)) for IVF/ICSI and 15.89 µg/l (90 % SN and 70 % SP) for IUI therapy. Logarithmic regression analysis also revealed a significant correlation between progesterone levels and live birth in IVF/ICSI and IUI therapy, with a p-value of < 0.001. Limitations, reasons for caution Low progesterone in early pregnancy may be a consequence or a cause for pregnancy demise. DYD, like any other progesterone for LPS, might adversely impact corpus luteum formation and maintenance through HPO axis interaction, especially in mono-ovulatory cycles or in older women with inherently higher risk of luteal phase defect. Wider implications of the findings Ovarian stimulation and hCG-administration may induce a luteal phase defect with insufficient luteal activity in early pregnancy, even up to luteolysis, with potential consequences for pregnancy maintenance and maternal/fetal health. Future treatment protocols may require exploring an optimal luteotropic state at pregnancy’s outset, necessitating the establishment of relevant markers. Trial registration number not applicable

Assessing the relationship between intrahepatic cholestasis of pregnancy and exogenous progesterone intake

Abstract Aim: Progesterone metabolites are known to be elevated in the serum of patients with intrahepatic cholestasis of pregnancy (ICP), and exogenous progesterone supplementation in early pregnancy may cause an increase in progesterone metabolites. The aim of this study is to investigate the relationship between ICP and exogenous progesterone intake. Materials and Methods: This study is a retrospective case-control study conducted between January 2015 and November 2023. The groups liver function tests, total bile acids, maternal age, body mass index, parity, history of cholestasis, history of progesterone use, gestational week in which pruritus symptoms occurred, gestational week, in which ICP was diagnosed, history of ursodeoxycholic acid intake, obstetric pathology, maternal comorbidities, week of delivery, delivery method, birth weight, APGAR scores were obtained from the database of our hospital and compared. Results: A total of 379 pregnant women including 79 with ICP and 300 control patients were included in the study. Nulliparity, history of cholestasis, and history of progesterone intake were significantly higher in the ICP group than in the control group. Conclusion: Intake of exogenous progesterone in early pregnancy may lead to ICP and have adverse effects on the fetus. Further studies are needed to investigate the role of progesterones in the development of ICP.

Progesterone in Pregnancy: Evidence-Based Strategies to Reduce Miscarriage and Enhance Assisted Reproductive Technology.

The incidence of miscarriage in early pregnancy, between 5-20 weeks, is common, with a prevalence of between 5-22% of all pregnancies. Miscarriage can have physical, social, and mental health impacts on women and their families. In societies such as Taiwan, where the birth rate is falling and life expectancy is increasing, there is concern that factors that reduce birth rates will have detrimental economic and societal effects. Progesterone has a significant role in maintaining early and successful pregnancy to term. Evidence from preclinical and clinical research on the roles of progesterone has supported recent clinical guidelines in obstetrics and gynecology to reduce rates of early miscarriage and improve methods of assisted reproductive technology (ART). This article aims to present an evidence-based review of current recommendations for the use of progesterone in early pregnancy to reduce miscarriage rates and in luteal phase support for ART, including embryo transfer.

P-760 Effect of relaxin on human endometrial stromal cell characteristics

Abstract Study question Does relaxin (RLX) regulate decidualization and pro- and antiangiogenic factors in primary human endometrial stromal cells (hESC), primary decidual cells (pD) and hTERT-immortalized hESC (T hESC)? Summary answer RLX treatment enhances decidualization and affects the mRNA expression levels of pro- and antiangiogenic factors. What is known already Patients undergoing frozen embryo transfer in an artificial cycle (AC-FET) are at a 2-fold increased risk for preeclampsia compared to embryo transfer in a natural cycle. This may be related to the absence of the corpus luteum in an artificial FET cycle, which produces important hormones such as estrogen and progesterone in early pregnancy. These hormones are supplied during AC-FET, whereas other products of the corpus luteum, such as RLX, are not. Low maternal RLX levels were found in women who developed preeclampsia, but the direct relationship between RLX and the occurrence of preeclampsia remains to be elucidated. Study design, size, duration Primary hESC were isolated from biopsies of women without endometrial pathology, pD cells from biopsies of the maternal side of the placenta of uncomplicated pregnancies and T hESC purchased from American Type Culture Collection. Cells were decidualized with either 0.5 mM cyclic adenosine monophosphate (cAMP) or a cocktail of 10 nM estradiol, 1 µM progesterone and 0.5 mM cAMP (EPC) and additionally treated with 0, 0.3 or 1 ng/ml RLX for twelve days. Participants/materials, setting, methods RNA was isolated on day zero and day twelve from all three cell types. mRNA expression level of decidualization markers (prolactin (PRL), insulin like growth factor binding protein 1 (IGFBP1)) as well as pro- and antiangiogenic factors (vascular endothelial growth factor (VEGF); placenta like growth factor (PlGF); soluble Fms-like tyrosine kinase-1 (sFlt-1); and endoglin (ENG)) were evaluated by quantitative real time polymerase chain reaction (qRT-PCR), N = 3 biological replicates. Main results and the role of chance Decidualization treatment of hESC with cAMP caused more noticeable changes to cell morphology than treatment with EPC. While there was no rise of decidualization markers PRL (p = 0.99) and IGFBP1 (p = 0.95) in the cAMP treatment group, hESC after EPC treatment showed a significant increase in both PRL (p = 0.0003) and IGFBP1 (p = 0.0001). RLX treatment in the EPC treated hESC and pD significantly increased the mRNA expression levels of PRL and IGFBP1 (both p < 0.05, respectively), as well as the expression of the proangiogenic marker VEGF (P = 0.05). A comparative analysis with T hESC showed a moderate effect on VEGF and PlGF. No effect of RLX was detected for IGFBP1 and PRL mRNA expression levels. The mRNA expression level of the antiangiogenic marker ENG increased in the EPC group in both, primary hESC (P = 0.04) and T hESC (P = 0.01) after treatment with 0.3 ng/ml RLX compared to control. ENG mRNA expression level increased in a dose dependent manner in pD but not in hESC and T hESC. RLX treatment with 1ng/ml of cAMP decidualized hESC significantly enhanced mRNA expression levels of VEGF (P = 0.002) and PlGF (P = 0.02) only in hESC but not in T hESC or pD. Limitations, reasons for caution Our pilot study indicates that RLX treatment improves decidualization and affects pro- and antiangiogenic factors in three different human endometrial stromal cell models. A wider approach is needed to investigate the effects of RLX in the decidualization process and pro- and antiangiogenic factors. Wider implications of the findings Our results provide the basis for further studies elucidating the relationship between low maternal RLX levels and the occurrence of preeclampsia. This could lead to the development of improved prediction models and new treatment options in assisted reproduction that reduce the risk of preeclampsia, e.g. in AC-FET. Trial registration number Not applicable

Mifepristone Antagonization with Progesterone to Avert Medication Abortion: A Scoping Review.

The safety and efficacy of mifepristone antagonization with progesterone to avert medication abortion, also known as abortion pill rescue, is a subject of vigorous debate. Two prominent medical associations have taken positions that either entirely reject or fully support its use. This scoping review aimed to gain insight into the safety and efficacy of its use. Analysis of 16 studies showed that the continuing pregnancy rate after ingesting mifepristone alone is ≦25 percent for gestational ages ≦49 days. Analysis of four studies showed that two-thirds of the women who changed their minds and received progesterone after initiating their medication abortion with mifepristone could safely continue their pregnancies. There is no increased maternal or fetal risk from using bioidentical progesterone in early pregnancy. If a woman has already taken mifepristone for her medication abortion and then changes her mind, timely supplementation with progesterone may allow her pregnancy to continue. The conclusion that mifepristone antagonization with progesterone is a safe and effective treatment has implications for medication abortion informed consent. Summary: Two-thirds of the women who changed their minds and received progesterone after initiating their medication abortion with mifepristone could safely continue their pregnancies. If a woman has already taken mifepristone for her medication abortion and then changes her mind, timely supplementation with progesterone may allow her pregnancy to continue. Physicians should disclose this treatment option to their patients at the time of informed consent.

Study of progesterone level during first trimester of pregnancy in cows.

Measurement of progesterone is an indirect method for pregnancy diagnosis in many livestock species including cattle, buffaloes, sheep, and goats. Conception extends the life of the corpus luteum (CL) by preventing the luteolytic mechanism from being triggered, thus prolonging and maintaining its functional characteristics, ensuring continued high progesterone levels (Spencer, et.al., 1995). (Shemesh et al., 1973) proposed that the difference in peripheral plasma progesterone levels between pregnant and non pregnant cows, 19 days after insemination, can form the basis for a very early pregnancy test. (Laing and Heap 1972) first documented this in milk to diagnose cows in early pregnancy Progesterone maintains the uterine endometrium in a state which supports embryonic development, implantation, and foetoplacental development. Progesterone concentrations vary with the stage of the estrous cycle which makes it one of the most commonly studied reproductive hormones in bovine ruminants for pregnancy detection and ovarian activity (Kaneko,et.al.,1994). Studies in the bovine estrous cycle indicate that the milk or serum progesterone concentrations reach a maximum value 13-14 days after estrus, and if the animal is pregnant, these continue to remain elevated up to day 21 after fertilization (Parkinson, et al.,1994) . These high levels of progesterone in serum or milk between days 18 and 24 after insemination form the basis of establishment of pregnancy in cattle (Sasser, and Ruder,1987; Shemesh,1973). Interferon-???? exerts its antiluteolytic effect by inhibiting the endometrial expression of oxytocin receptors, through which oxytocin stimulates pulsatile PGF2???? release (Wolf,2003). Although low progesterone concentrations at 18 to 24 days after breeding can accurately predict non pregnancy, high progesterone concentrations during this period are not the specific indicators of pregnancy due to variations among cows in duration of the estrous cycle as well as the incidence of early or late embryonic mortality. The advantages of progesterone assay for pregnancy diagnosis include noninvasive collection of milk sample and the feasibility to conduct the test on the farm using commercial cow-side milk progesterone test kits [Pennington,1985 ; Gowan,1982 ; Wimpy,et.al.,1986), though the sensitivity gets compromised to some extent with these assay kits.
 Key Word: progesterone, pregnancy, cows

P-362 The association between pregnancy-test day serum progesterone in IVF pregnancies and obstetrical complications

Abstract Study question Is there an association between pregnancy-test day serum progesterone level in IVF pregnancies and late gestational complications? Summary answer Low serum progesterone on pregnancy diagnosis day is independently associated with a higher prevalence of preeclampsia. What is known already Low first trimester arbitrary serum progesterone is associated with early pregnancy complications such as ectopic pregnancies and miscarriages. IVF pregnancies are associated with higher prevalence of obstetrical complications such as preterm birth, preeclampsia and small for gestational age. Different patient and treatment parameters such as age, diagnosis, peak blood Estradiol level, endometrial thickness, fresh or frozen embryo transfer are associated with obstetrical complications. Progesterone is a potent immunomodulator that can affect the inflammatory pathway and trophoblast invasion. Little is known about the association between early pregnancy progesterone level and obstetrical complications, with conflicting results. Study design, size, duration A cohort study reviewing fertility and delivery files of all singleton live births from successfully treated infertile patients, who underwent ovarian stimulation, IVF and fresh embryo transfer in a tertiary medical center between 2008 and 2018. Participants/materials, setting, methods Serum progesterone concentration was measured with the first serum hCG on 4 + 0 gestational week (14 days after oocyte retrieval) under luteal support with vaginal progesterone. Pregnancy-test day serum progesterone was categorized in quartiles. The prevalence of obstetrical complications including gestational diabetes mellitus, preterm birth, preeclamsia, small for gestational age, post-partum hemorrhage and neonatal ICU hospitalization was compared between the four groups. Confounders were adjusted for by multivariate analysis. Main results and the role of chance 719 singleton live births were included. The four serum progesterone quartiles were: Q1:3-44 nmol/L(n = 180); Q2:45-107 nmol/L(n = 180); Q3:108-223 nmol/L(n = 178); Q4:225-808nmol/L(n = 181). Patients with lower progesterone levels (Q1) had significantly more IVF treatments, lower peak estradiol level, fewer mature follicles and frozen embryos. The incidence of preterm labor, gestational diabetes mellitus, small-for-gestational-age, post-partum hemorrhage, placental abruption or neonatal ICU administration did not differ between the groups. Patients with lower serum progesterone had higher incidence of preeclampsia (9.44% in Q1, 2.78% in Q2, 2.81% in Q3 and 3.31% in Q4, P = 0.0046). On multivariate analysis, controlling for age, gravidity, treatment number, number of oocytes, peak follicular estradiol and progesterone, Q1 progesterone level was independently associated with an increased risk of preeclampsia (estimated OR = 3.27 95% CI 1.455-7.299). Limitations, reasons for caution Retrospective design, vaginal progesterone luteal support administration. Wider implications of the findings Low serum progesterone on pregnancy diagnosis day in gestations resulting from fresh ET is associated with a significantly higher prevalence of preeclampsia, possibly because of aberrant placentation and vascular development. This association is important for the obstetrical management, preeclampsia risk assessment, and administration of preventive therapy. Trial registration number not applicable

Corpus luteum score, a simple Doppler examination to prognose early pregnancies

ObjectivesIn early pregnancies, miscarriages and inconclusive ultrasound scans considering location and viability are very common. In several previous studies, serum progesterone levels predicted viability of pregnancy and, in recent ones, failed Pregnancies of Unknown Location (PUL), completion of miscarriage and complications. Corpus luteum, secreting progesterone in early pregnancy, was less studied. Some publications showed correlations between corpus luteum aspects and diagnosis of miscarriage but it was not evaluated for other outcomes in early pregnancy, such as failed PUL, completion of miscarriage or complications. We aimed to assess if Doppler examination of corpus luteum could also predict all these outcomes: failed PUL, diagnosis and completion of miscarriages and complications. Study designA single operator prospectively described and/or collected pictures of Doppler signal in the wall of the corpus luteum at most consultations in our early pregnancy unit and established a three-level score. All suspected or confirmed non-viable pregnancies with this score or/and serum progesterone levels were registered retrospectively. With logistic regressions, AIC/BIC, likelihood ratios, ROC curves, Mann-Whitney and Fisher exact tests, we evaluated the ability of the score, alone, to predict failed PUL, diagnosis and completion of miscarriages and the complications, and, combined, to improve previously published predictions. ResultsFrom 277 included pregnancies, 186 (67.1 %) miscarried. Of these, 159/186 (85.5 %) fully evacuated without surgery: 114/186 (61.3 %) within 20 days after the first diagnosis and 45/186 (24.2 %) after more than 20 days. Twenty-seven patients (14.5 %) underwent surgical evacuation, including ten complications, five haemorrhages and five suspected infections. Logistic regression correlated strongly the corpus luteum score with failed PUL (p < 0.0001) and miscarriages (p < 0.0001). Moreover, rates of complications and swift non-surgical completions of miscarriage were respectively 0 % and 92 % with scores of 0, versus 6 % and 44 % with scores of 1, versus 16 % and 0 % with scores of 2. Combined with serum progesterone levels, this score improved most predictions. Adding parity or history of miscarriage in predictive models even increased these performances. ConclusionsCorpus luteum score, alone, can predict failed PUL, diagnosis and completion of miscarriages and their complications. Combining this score with other factors (mainly serum progesterone levels) improves most predictions.

Early pregnancy maternal progesterone administration alters pituitary and testis function and steroid profile in male fetuses

Maternal exposure to increased steroid hormones, including estrogens, androgens or glucocorticoids during pregnancy results in chronic conditions in offspring that manifest in adulthood. Little is known about effects of progesterone administration in early pregnancy on fetal development. We hypothesised that maternal early pregnancy progesterone supplementation would increase fetal progesterone, affect progesterone target tissues in the developing fetal reproductive system and be metabolised to other bioactive steroids in the fetus. We investigated the effects of progesterone treatment during early pregnancy on maternal and fetal plasma progesterone concentrations, transcript abundance in the fetal pituitary and testes and circulating steroids, at day 75 gestation, using a clinically realistic ovine model. Endogenous progesterone concentrations were lower in male than female fetuses. Maternal progesterone administration increased male, but not female, fetal progesterone concentrations, also increasing circulating 11-dehydrocorticosterone in male fetuses. Maternal progesterone administration altered fetal pituitary and testicular function in ovine male fetuses. This suggests that there may be fetal sex specific effects of the use of progesterone in early pregnancy, and highlights that progesterone supplementation should be used only when there is clear evidence of efficacy and for as limited time as necessary.

Progestogen for treating threatened miscarriage.

Miscarriage is a common complication encountered during pregnancy. It is defined as spontaneous pregnancy loss before 20 weeks' gestation. Progesterone's physiological role is to prepare the uterus for the implantation of the embryo, enhance uterine quiescence and suppress uterine contractions, hence, it may play a role in preventing rejection of the embryo. Inadequate secretion of progesterone in early pregnancy has been linked to the aetiology of miscarriage and progesterone supplementation has been used as a treatment for threatened miscarriage to prevent spontaneous pregnancy loss. This update of the Cochrane Review first published in 2007, and previously updated in 2011, investigates the evidence base for this practice. To determine the efficacy and the safety of progestogens in the treatment of threatened miscarriage. We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (8 August 2017) and reference lists of retrieved trials. Randomised, quasi-randomised or cluster-randomised controlled trials, that compared progestogen with placebo, no treatment or any other treatment for the treatment of threatened miscarriage in women carrying singleton pregnancy. At least two review authors assessed the trials for inclusion in the review, assessed trial quality and extracted the data and graded the body of evidence. We included seven trials (involving 696 participants) in this update of the review. The included trials were conducted in different countries, covering the full spectrum of the World Bank's economic classification, which enhances the applicability of evidence drawn from this review. Two trials were conducted in Germany and Italy which are high-income countries, while four trials were conducted in upper-middle income countries; two in Iran, one in Malaysia and the fourth in Turkey, and the seventh trial was conducted in Jordan, which is a lower-middle income country. In six trials all the participants met the inclusion criteria and in the seventh study, we included in the meta-analysis only the subgroup of participants who met the inclusion criteria. We assessed the body of evidence for the main outcomes using the GRADE tool and the quality of the evidence ranged from very low to moderate. Downgrading of evidence was based on the high risk of bias in six of the seven included trials and a small number of events and wide confidence intervals for some outcomes.Treatment of miscarriage with progestogens compared to placebo or no treatment probably reduces the risk of miscarriage; (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.47 to 0.87; 7 trials; 696 women; moderate-quality evidence). Treatment with oral progestogen compared to no treatment also probably reduces the miscarriage rate (RR 0.57, 95% CI 0.38 to 0.85; 3 trials; 408 women; moderate-quality evidence). However treatment with vaginal progesterone compared to placebo, probably has little or no effect in reducing the miscarriage rate (RR 0.75, 95% CI 0.47 to 1.21; 4 trials; 288 women; moderate-quality evidence). The subgroup interaction test indicated no difference according to route of administration between the oral and vaginal subgroups of progesterone.Treatment of preterm birth with the use of progestogens compared to placebo or no treatment may have little or no effect in reducing the rate of preterm birth (RR 0.86, 95% CI 0.52 to 1.44; 5 trials; 588 women; low-quality evidence).We are uncertain if treatment of threatened miscarriage with progestogens compared to placebo or no treatment has any effect on the rate of congenital abnormalities because the quality of the evidence is very low (RR 0.70, 95% CI 0.10 to 4.82; 2 trials; 337 infants; very-low quality evidence). The results of this Cochrane Review suggest that progestogens are probably effective in the treatment of threatened miscarriage but may have little or no effect in the rate of preterm birth. The evidence on congenital abnormalities is uncertain, because the quality of the evidence for this outcome was based on only two small trials with very few events and was found to be of very low quality.

Early pregnancy sex steroids during primiparous pregnancies and maternal breast cancer: a nested case\u2013control study in the Northern Sweden Maternity Cohort

BackgroundPregnancy and parity are associated with subsequent breast cancer risk. Experimental and epidemiologic data suggest a role for pregnancy sex steroid hormones.MethodsWe conducted a nested case–control study in the Northern Sweden Maternity Cohort (1975–2007). Eligible women had provided a blood sample in the first 20 weeks of gestation during a primiparous pregnancy leading to a term delivery. The current study includes 223 cases and 417 matched controls (matching factors: age at and date of blood collection). Estrogen receptor (ER) and progesterone receptor (PR) status was available for all cases; androgen receptor (AR) data were available for 41% of cases (n = 92). Sex steroids were quantified by high-performance liquid chromatography tandem mass spectrometry. Odds ratios (ORs) and 95% confidence intervals were estimated using conditional logistic regression.ResultsHigher concentrations of circulating progesterone in early pregnancy were inversely associated with ER+/PR+ breast cancer risk (ORlog2: 0.64 (0.41–1.00)). Higher testosterone was positively associated with ER+/PR+ disease risk (ORlog2: 1.57 (1.13–2.18)). Early pregnancy estrogens were not associated with risk, except for relatively high estradiol in the context of low progesterone (split at median, relative to low concentrations of both; OR: 1.87 (1.11–3.16)). None of the investigated hormones were associated with ER–/PR– disease, or with AR+ or AR+/ER+/PR+ disease.ConclusionsConsistent with experimental models, high progesterone in early pregnancy was associated with lower risk of ER+/PR+ breast cancer in the mother. High circulating testosterone in early pregnancy, which likely reflects nonpregnant premenopausal exposure, was associated with higher risk of ER+/PR+ disease.

Drug exposure in early pregnancy might be related to the effects of increased maternal progesterone in implantation period

Aim: This short communication aims to evaluate the relation in between drug exposure time and early pregnancy regarding gestational weeks.Methods: The study covers the referrals made to the Department of Pharmacology for a teratogenic consultation in a 3-year period. From the recordings of pregnant women, the last menstrual period and the starting date of medication were used to determine the time of prescription with regard to gestational weeks.Results: In all of the three years, potentially teratogenic medication was prescribed more frequently in the 3rd, 4th and 5th gestational weeks (in between 15–35 days of pregnancy). Approximately 75% of the pregnant women in the study were prescribed with drugs, most frequently with analgesics, antibiotics, gastrointestinal drugs and antidepressants, in these gestational weeks.Conclusions: The timing of prescriptions in early pregnancy frequently coincides with the increased levels of maternal progesterone in implantation period. Progesterone may lead to negative mood symptoms of an increased pain perception, anxiety, irritability and aggression in some of the pregnant women and therefore causes an increased stress condition which in turn may result in pain, infection and inflammation in the individual. Taking the frequently used medications into consideration, the reason for prescriptions in this period might be related to the symptoms originating from the effects of progesterone. Future studies are needed to better demonstrate this association of drug exposure and effects of maternal progesterone in early pregnancy.

Association of maternal serum progesterone in early pregnancy with low birth weight and other adverse pregnancy outcomes

Objective: To investigate the association of serum progesterone in first trimester with low birth weight (LBW, birth weight <2500 g) and other adverse pregnancy outcomes including hypertensive disorders of pregnancy, preterm delivery, premature rupture of membranes at term, and preterm premature rupture of membranes in a general population.Methods: We conducted a cohort study of 263 women with low-risk singleton intrauterine pregnancies who had a spot serum progesterone measurement in the first trimester in a Singapore tertiary maternity hospital. Study outcomes were retrieved from clinical records. Follow-up data were available for 131 women. Univariate and multivariate logistic regression analyses were performed to assess the association of low serum progesterone (<35 nmol/L) with LBW and other adverse pregnancy outcomes.Results: Low serum progesterone was associated with a significantly increased risk of LBW (adjusted odds ratio: 5.28 [1.02, 27.3]; p=0.047). Low serum progesterone was associated with a significantly increased risk of hypertensive disorders of pregnancy in univariate analysis (unadjusted odds ratio: 8.43 [1.31, 54.2]; p=0.025).Conclusion: Low serum progesterone in the first trimester is a significant risk factor for LBW and possibly other placental dysfunction disorders such as hypertensive disorders of pregnancy. Further studies with larger sample sizes are needed to confirm the associations.

New insights into the function of progesterone in early pregnancy

New insights into the function of progesterone in early pregnancy

Monitoring blood plasma leptin and lactogenic hormones in pregnant sows

The mechanism of action of leptin in pregnant breeding sows, in which hyperphagia is managed through dietary strategies, is yet to be clarified. The aim of this study was to monitor leptin concentrations and their interactions with lactogenic hormones in Large White×Landrace breeding multiparous sows (n=15). All sows showed a normal body condition (mean body condition score: 2.96). Blood samples were collected the day after weaning the litters, at insemination, every 15 days up to day 45 of pregnancy and every 7 days from day 46 to farrowing. At delivery, the placenta was collected for the analysis of leptin and leptin receptor expressions. Plasma leptin levels increased from the end of mid gestation (day 72) and remained high until farrowing (P<0.05). As expected, plasma prolactin (PRL), low during most of pregnancy, increased during the 2 weeks before farrowing (P<0.05), whereas progesterone levels reached plateau at 30 days of gestation and decreased at farrowing (P<0.05). Cortisol levels peaked close to farrowing (P<0.05). Leptin was expressed in the placenta, where the receptor expression analysis showed the presence of the short form but not of the long form. A positive correlation was found between leptin and PRL concentrations during mid (r=0.430; P<0.001) and late (r=0.687; P<0.001) pregnancy, and with progesterone in early pregnancy (r=0.462; P<0.05). During late gestation, a positive correlation was observed between leptin and cortisol (r=0.585; P<0.001). Our results suggested that, in restrictively fed pregnant sows, the leptin levels increased from the end of mid pregnancy to delivery, confirming the presence of leptin resistance. We showed a correlation between leptin and lactogenic hormones during different stages of pregnancy in sows. Lactogenic hormones show pregnancy-specific changes in their secretion and all may become involved in modulating leptin signal.

Progesterone Within Ovulatory Menstrual Cycles Needed for Cardiovascular Protection: An Evidence-Based Hypothesis

Women experience acute myocardial infarctions (AMI) 10 years later than men – evidence that estrogen is protective is not consistent. Ovulatory disturbances (low progesterone but normal estradiol levels) silently occur in &gt;33% of all cycles. Progesterone-based (cycle-timed serum or saliva) levels or urinary metabolite excretions are necessary to diagnose silent ovulatory disturbances within regular, normal length menstrual cycles. Progesterone acts biphasically in vitro – initial proliferation changes to differentiation. It also suppresses or complements estradiol’s actions. Basic and clinical studies show that progesterone is positively related to endothelial function/blood flow, influences vascular smooth muscle cells and cardiac electrical signals. Several studies in primates document that high fat-fed subordinate females have higher stress, fewer ovulatory cycles and lower progesterone levels but similar cycle lengths as menstruating, dominant females. Subordinate females develop arterial plaque similar to high fat-fed males. In population-based prospective data, women with early pregnancy progesterone deficiency, stress and multiple miscarriages are at five-fold higher AMI risk. Also, early menopausal AMI are associated with significantly more pre-/perimenopausal anovulatory cycles. Given the multi-dimensional positive effects of progesterone on the cardiovascular system (CVS), and persuasive data from primate and human studies associating increased AMI with ovulatory disturbances, this review presents a new CVS protection hypothesis for women – ovulatory cycles with balanced progesterone-estradiol levels decrease women’s risks for AMI. Based on this new theory, it is believed that progesterone as well as estradiol is required during the premenopausal years to prevent women’s early heart disease.

Микронизированный прогестерон: некоторые аспекты профилактики невынашивания беременности

Progesterone is an essential hormone in the process of reproduction. Progesterone offers an effective intervention when the continuation of pregnancy is at risk from immunological factors, luteinic and neuroendocrine deficiencies, and myometrial hypercontractility. Progesterone has been successfully used as prophylaxis in the prevention of spontaneous miscarriage, with treatment beginning from the first trimester of pregnancy. There is substantial evidence, too, to indicate that women with idiopathic recurrent miscarriage may benefit from the immunomodulatory properties of progesterone in early pregnancy. The use of progesterone has been extensively studied in the prevention of preterm birth in a variety of settings. This paper reviews the evidence for the safety and efficacy of the use of progesterone in each of these indications.

The role of progesterone in maternal and fetal medicine

Progesterone is an essential hormone in the process of reproduction. It has been extensively studied in the treatment of different gynecological pathologies, as a contraceptive and in assisted reproductive technologies. However, the use of progesterone in the pathophysiology of pregnancy remains controversial. Progesterone, and its synthetic form 17 α-hydroxyprogesterone caproate (17 OHP-C), offer an effective intervention when the continuation of pregnancy is at risk from immunological factors, luteinic and neuroendocrine deficiencies, and myometrial hypercontractility. Progesterone has been successfully used as prophylaxis in the prevention of spontaneous miscarriage, with treatment beginning from the first trimester of pregnancy. There is substantial evidence, too, to indicate that women with idiopathic recurrent miscarriage may benefit from the immunomodulatory properties of progesterone in early pregnancy. The use of progesterone and 17 OHP-C has been extensively studied in the prevention of preterm birth in a variety of settings. Transvaginal ultrasound measurement of cervical length in singleton pregnancies between 19 and 24 weeks’ gestation has been deemed the best way to identify women (approximately 2% of the pregnant population) who would benefit from prophylactic progesterone treatment for the prevention of spontaneous preterm birth. This paper reviews the evidence for the safety and efficacy of the use of progesterone in each of these indications.

Progesterone supplementation in women with otherwise unexplained recurrent miscarriages

CONTEXT:Recurrent miscarriages, the loss of three or more consecutive intrauterine pregnancies before 20 weeks of gestation with the same partner, affect 1%–1.5% of the pregnant population. The inadequate secretion of progesterone in early pregnancy has been proposed as a cause of recurrent miscarriages.AIMS:The aim was to investigate the efficacy of progesterone supplementation in patients with unexplained recurrent miscarriages.SETTINGS AND DESIGN:This was a 9-year cohort study of women with otherwise unexplained recurrent miscarriages who attended a recurrent miscarriage clinic in a tertiary care university hospital.SUBJECTS AND METHODS:Women with at least three unexplained recurrent miscarriages were included in the study. They were divided into three groups according to their initial and 48-h repeat progesterone levels. For women with inadequate endogenous progesterone secretion, natural progesterone vaginal pessaries 400 mg 12-hourly were offered until 12 weeks gestation.STATISTICAL ANALYSIS:Proportions and 95% confidence intervals calculated for categorical variables and the chi-square test were used to show statistical significance. Medians and ranges were calculated for noncontinuous variables.RESULTS:Pregnancy cycles (n = 203) were analyzed to examine the miscarriage rate following progesterone supplementation. Overall live birth and miscarriage rates were 63% and 36%, respectively. When analyzed by the number of previous miscarriages there was a reduction in the miscarriage rate following progesterone supplementation in women with 4 previous miscarriages when compared with historical data.CONCLUSIONS:Progesterone supplementation may have beneficial effects in women with otherwise unexplained recurrent miscarriages.

Immunological actions of progesterone in early pregnancy

Immunological actions of progesterone in early pregnancy