Exogenous Progesterone Research Articles

O-011 Is there a need for LH surge inhibition by GnRH-antagonists in luteal phase stimulation in poor ovarian responders undergoing Duostim? Efficacy of natural progesterone

Abstract Study question Is there a need for LH surge inhibition by GnRH-antagonists in luteal phase stimulation in poor ovarian responders undergoing Duostim? Summary answer Inhibition of the LH surge by progesterone during the luteal phase of duostim protocols in POR appears to be effective, safe and makes GnRH-antagonists unnecessary. What is known already High levels of progesterone have long been shown to reversibly block the LH surge associated with increased estradiol levels, by reducing GnRH’s pulsatility from the hypothalamus. This inhibition is the basis of progestin-only contraceptives and has been shown to be completely reversible by discontinuing the progestin, and even seems to have a potentiating effect on the surge which occurs in the subsequent few days Study design, size, duration This is a secondary analysis of the BISTIM study, a multicentre, open-labelled randomized controlled trial, performed in 4 french IVF centers from 2018 to 2021, designed to compare Duostim protocol versus two follicular stimulations. We here present a paired-controlled study including patients randomized in the Duostim group, who underwent 2 consecutive stimulations in the same menstrual cycle, we compare the follicular phase stimulation with GnRH-antagonist versus the luteal phase stimulation with progesterone. Participants/materials, setting, methods The BISTIM study recruited poor ovarian reserve women defined with Bologna criteria who enrolled in an IVF or ICSI program, aged from 20 to 41, with BMI from 19 to 32, with no more than 2 previous IVF cycles. Women with amenorrhea, FSH >20 UI/L or CFA <1 were not included. 32 of them underwent two stimulations, consecutively. Main results and the role of chance For the same group of 32 women, stimulation parameters were similar between 1st and 2nd stimulations (stimulation duration, gonadotropin doses, number of retrieved oocytes). As expected, progesterone levels were significantly higher at D5 in the study group compared to controls (mean 34.8 ng/ml, Q1-Q3 [18.4 – 51.6])) and were still significantly higher at HCG-day (10.7 ng/ml, Q1-Q3 [2.7 – 14.3])), despite the addition of natural exogenous progesterone. LH levels were significantly lower in the progesterone group, regardless of the day of stimulation: at HCG day mean LH was 1,7 UI/L in the study group versus 6.8 UI/L in the control group, p < 0.001. In the Duostim group no premature LH surge/ovulation was observed, however, 2 cancellations for premature ovulation were reported with antagonist protocol in the control group of the BISTIM study. Limitations, reasons for caution This study was carried out on a limited number of subjects (n = 32), all of whom were poor responders. Wider implications of the findings This study shows the effectiveness of LH surge inhibition by progestins, which represent a less expensive and more patient-friendly treatment than traditional protocols. Further studies are needed to determine the best protocol (type and doses of progestins) to effectively inhibit the LH surge, and on larger and different cohorts. Trial registration number 2017-A00498-45

P-701 Impact of vaginal microbiome on vaginal absorption of exogenous progesterone: a pilot study

Abstract Study question Does vaginal microbiome have an impact on vaginal absorption of exogenous progesterone (P intake) in artificial cycles? Summary answer Results suggest that the presence of lactobacillus in the vagina may positively impact the uptake of P. What is known already Low serum P levels on ET day decrease significantly live birth rates. About 20% of patients receiving micronized vaginal P show inadequate levels. It is of interest to find out which intrinsic factors might influence on the capacity of absorption (P intake) of vaginal P, and if they could be treated to prevent this situation. Vaginal microbiome hast been suggested as a possible factor, although this has not been addressed yet. The aim of this study was to explore if there is a correlation between vaginal microbiome and pH, and P intake. Study design, size, duration A prospective single-centre cohort pilot study including 92 ART patients was conducted from February 2022 to January 2023 in IVI-RMA Valencia. Embryo transfer was conducted in the context of a hormonal replacement therapy cycle with use of vaginal P (400mg/12h) for luteal phase support. “Progesterone intake” capacity was evaluated according to the vaginal microbiome status (lactobacillus dominant (LDM, >90%) or non-lactobacillus dominant (NLDM) and pH levels determinations (considered normal when moderately acidic ( < =4.8). Participants/materials, setting, methods Samples were taken twice: A) proliferative phase (day of initiation of exogenous P) and B) mid-luteal phase (day of ET, P + 5). Serum E2 and P levels as well as vaginal microbiome and pH were analysed. A validated qPCR methodology was used to accurately assess the presence and relative abundance of the four major lactobacillus species associated with eubiosis (crispatus, gasseri, iners, and jensenii) and the most common bacterial species implicated in dysbiosis. Main results and the role of chance Distribution of LDM and NLDM profiles were comparable between Samples A and B. No significant difference between any of the potential confounding factors (age, BMI,baseline P) between the lactobacillus CST groups (CST-I,-II,-III,-V & lactobacillus) and the dysbiotic CST group (CST-IV) in Samples A and B were observed. Serum P levels on the ET day were significantly higher in LDM profiles both in Sample A (15.2 vs. 12.9ng/mL in NLDM;p=0.009) and B (15.0 vs. 12.8ng/mL;p=0.014). A positive significant correlation was found between serum P levels and Lactobacillus abundance in Samples A (r = 0.28; p = 0.008) and B (r = 0.30; p = 0.004). The relative abundance of Gardnerella vaginalis in Sample A was negatively related to serum P levels on the ET day (r=-0.24;p=0.02). Vaginal pH was significantly lower in LDM profiles both in Sample A (4.9 vs. 5.6 in NLDM; p = 0.002) and B (4.7 vs. 5.1;p<0.001). pH levels were negatively correlated with Lactobacillus abundance in Samples A (r=-0.34;p=0.0012) and B (r=-0.41;p<0.001). Additionally, serum P levels were negatively correlated with pH levels in Sample A (r=-0.14;p=0.191) and B (r=-0.27; p = 0.010). Indeed, when patients are grouped based on a cut-off of P = 8.8ng/mL, patients with a pH ≤ 4.8 have significantly higher P levels than patients with a pH > 4.8. Limitations, reasons for caution This is a pilot study, thus further trials with larger sample sizes should be performed in order to confirm these results. Additionally, vaginal microbiome alone does not explain the total variability in serum P levels measured in artificial cycles when using MVP. Wider implications of the findings We might have found one of the causes of the high heterogeneity on vaginal absorption of MVP in artificial cycles. This finding may help us with patient management when programming an ET in this type of cycles, improving personalised patient care and progressing on luteal phase support individualisation. Trial registration number 2110-VLC-095-EL

Does Serum Estradiol Prior to Progesterone Administration in Programmed Frozen Embryo Transfer Cycle Impacts Live Birth Rate: A Prospective Cohort Study.

There is a paucity of data on the optimal threshold of oestradiol (E2) levels required for successful implantation as this is a valid question to be answered, considering that significant number of in vitro fertilisation cycles are deferred for FET cycles. The aim of this study is to investigate the serum E2 levels before starting exogenous progesterone in artificial autologous frozen thawed embryo transfers on pregnancy outcomes. This was a cohort study wherein clinical data of 213 artificial autologous programmed hormone-regulated frozen embryo transfer (HR-FET) cycles were collected. The HR-FET cycles were divided into three groups based on the E2 levels before starting progesterone: Group A: E2 ≤300 pg/mL, Group B: E2 301-500 pg/mL and Group C: E2 >500 pg/mL. After adequate endometrial stripe was appreciated by transvaginal ultrasonography, single blastocyst transfer was performed in all the cycles. The clinical pregnancy rate (CPR) in Groups A, B and C were 41.8%, 73.5% and 0.95%, respectively (P = 0.0001). The live birth rate (LBR) in Groups A, B and C was 18.1%, 62.2% and 0%, respectively (P = 0.0001). The miscarriage rate (MR) was significantly lower (15.3%) when E2 was between 301 and 500 pg/mL (P = 0.001). At both the extremes of serum E2 values, the rate of miscarriage increased. If serum E2 levels were ≤300 pg/mL or >500 pg/mL, the rate of miscarriage was 56.5% and 100%, respectively. Serum E2 levels in the range of 301-500 pg/mL before starting progesterone in programmed FET cycle are associated with an improved CPR and LBR and also decreased MR as compared to the extreme values of E2 ≤300 pg/mL or >500 pg/mL.

Progesterone in frozen embryo transfer cycles: assays, circulating concentrations, metabolites, and molecular action

Programmed or medicated frozen embryo transfer (FET) cycles rely on exogenous progesterone (P) administration to prepare the endometrium for implantation and to maintain pregnancy. Presently, the optimal route and dose of P replacement for FET is not known. In addition, there is a paucity of data and insufficient understanding regarding the metabolism and actions of P in implantation and pregnancy maintenance. In the present review, we discuss how different P assay methodologies affect the determination of P thresholds for implantation and pregnancy maintenance. In addition, we discuss the importance of free P and its regulation in the endometrium and show the complexity of molecular signaling that is required for P-dependent endometrial receptivity. We conclude that future studies should focus on defining accurate circulating and endometrial P concentrations, both for total and free P, and how these concentrations correlate with endometrial receptivity and clinical outcomes.

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.

E024 A pregnant woman with vasculitis and a new rash

Abstract Background/Aims A 41-year-old pregnant woman at 16 weeks of gestation was followed-up in the combined obstetric and rheumatology clinic as she had a history of eosinophilic granulomatosis with polyangiitis (EGPA) and two previous miscarriages at first trimester. Her vasculitis was well-controlled with a baseline daily dose of prednisolone 7.5mg. Methods During her pregnancy, she started on vaginal progesterone by the IVF (In Vitro Fertilization) team for pregnancy support following a vaginal bleed. During her second review in clinic, she complained about a widespread pruritic rash for the last 3 weeks. She had already been seen by her GP who prescribed her emollients without any improvement. On examination, the active lesions looked urticarial and were tender. There was also residual hyperpigmentation. The lesions persisted for more than 24 hours before spontaneous resolution. Cutaneous vasculitis was suspected based on the duration of the rash more than 24 hours, the hyperpigmentation, tenderness, and the history of EGPA. Otherwise, she was well in herself with no symptoms of active vasculitis and no recent infections. Therefore, prednisolone was increased to 15mg daily and loratadine was given for the pruritus. Her repeat blood tests were reassuring with negative ANCA, normal C3 and C4, CRP, and eGFR. Results During her early follow-up, the rash was the same despite the higher dose of steroids and she volunteered that the rash is worse in the morning and at night. Autoimmune progesterone dermatitis (AIPD) was considered then. AIPD is a rare autoimmune hypersensitivity reaction to endogenous or exogenous progesterone. AIPD varies greatly from patient to patient and can present as urticaria, eczema or vesiculobullous eruptions. Urticarial or EGPA vasculitis, and urticaria would have improved with steroids. Furthermore, she did not have any symptoms suggestive of systemic vasculitis and the relevant blood tests were also normal. Of note, the rash was worse in the morning and at night, which corresponded to the time of vaginal exposure to progesterone. The patient stopped the progesterone pessaries after discussion with the obstetrician. The rash improved gradually and resolved in five days, confirming the diagnosis of AIPD. Conclusion The rash could have been mistaken for urticaria or vasculitis. Consequently, the patient may have had unnecessarily antihistamines and steroids during pregnancy with all relevant side effects, such as gestational diabetes. In November 2021, NICE recommended vaginal progesterone in women who experience bleeding in early pregnancy and have a history of miscarriage as it slightly reduces the risk of a further miscarriage. The new guidelines suggest that more pregnant women will use topical progesterone during pregnancy who may develop AIPD. This means that we are going to see more pregnant women in the rheumatology clinic with AIPD and the rheumatology community should be aware of this entity. Disclosure A. Madenidou: Grants/research support; Janssen. H. Kither: None. I. Bruce: Consultancies; AstraZeneca, GSK, Eli Lilly, and UCB. Honoraria; AstraZeneca, GSK, and UCB. Grants/research support; AstraZeneca, GSK, and Janssen.

Women at Altitude: Menstrual-Cycle Phase, Menopause, and Exogenous Progesterone Are Not Associated with Acute Mountain Sickness.

Gardner, Laurel, Linda E. Keyes, Caleb Phillips, Elan Small, Tejaswi Adhikari, Nathan Barott, Ken Zafren, Rony Maharjan, and James Marvel. Women at altitude: Menstrual-cycle phase, menopause, and exogenous progesterone are not associated with acute mountain sickness. High Alt Med Biol. 00:000-000, 2024. Background: Elevated progesterone levels in women may protect against acute mountain sickness (AMS). The impact of hormonal contraception (HC) on AMS is unknown. We examined the effect of natural and exogenous progesterone on the occurrence of AMS. Methods: We conducted a prospective observational convenience study of female trekkers in Lobuche (4,940 m) and Manang (3,519 m). We collected data on last menstrual period, use of exogenous hormones, and development of AMS. Results: There were 1,161 trekkers who met inclusion criteria, of whom 307 (26%) had AMS. There was no significant difference in occurrence of AMS between women in the follicular (28%) and the luteal (25%) phases of menstruation (p = 0.48). The proportion of premenopausal (25%) versus postmenopausal women (30%) with AMS did not differ (p = 0.33). The use of HC did not influence the occurrence of AMS (HC 23% vs. no HC 26%, p = 0.47), nor did hormonal replacement therapy (HRT) (HRT 11% vs. no HRT 31%, p = 0.13). Conclusion: We found no relationship between menstrual-cycle phase, menopausal status, or use of exogenous progesterone and the occurrence of AMS in trekkers and conclude that hormonal status is not a risk factor for AMS. Furthermore, women should not be excluded from future AMS studies based on hormonal status.

Can single progesterone concentration predict miscarriage in early pregnant women with threatened miscarriage: a systematic review and meta-analysis

BackgroundAbout 25% of pregnant women experience bleeding in the early stage, and half of them eventually progress to pregnancy loss. Progesterone serves as a useful biomarker to predict miscarriage in threatened miscarriage, yet its performance is still debated.AimTo evaluate the performance of single serum progesterone predicting miscarriage in early pregnant patients with threatened miscarriage.MethodThe online database was searched to yield the literature using the terms of ‘Abortion’, ‘Miscarriage’, and ‘serum Progesterone’, including PubMed, Scopus, Embase, Cochrane library, and China national knowledge infrastructure. Receiver operating characteristic (ROC) curve, likelihood ratio (LLR) and diagnostic odds ratio (DOR) and 95% confidence interval (CI) were computed. Publication bias was assessed by the deeks funnel plot asymmetry test. Subgroup analyses were conducted according to the progesterone level (< 12 ng/mL), recruited location and region, progesterone measurement method, exogenous progesterone supplement and follow up.ResultsIn total, 12 studies were eligible to be included in this study, with sample sizes ranging from 76 to 1087. The included patients’ gestational age was between 4 and 12 weeks. No significant publication bias was detected from all included studies. The threshold of progesterone reported ranged from 8 to 30 ng/ml. The synthesized area under the ROC curve (0.85, 95% CI 0.81 to 0.88), positive LLR (6.2, 4.0 to 9.7) and DOR (18, 12 to 27) of single progesterone measurement distinguishing miscarriage were relatively good in early pregnant patients with threatened miscarriage. When the threshold of < 12 ng/mL was adapted, the progesterone provided a higher area under the ROC curve (0.90 vs. 0.78), positive LLR (8.3 vs. 3.8) and DOR (22 vs.12) than its counterpart (12 to 30 ng/mL).ConclusionSingle progesterone measurement can act as a biomarker of miscarriage in early pregnant patients with threatened miscarriage, and it has a better performance when the concentration is <12 ng/mL.Trial registrationPROSPERO (CRD42021255382).

Ideal frozen embryo transfer regime.

This review aims to compare evidence on four criteria (embryo implantation, obstetric outcomes, patient convenience, and IVF-unit efficiency) by analyzing published research on different endometrial preparation methods for frozen embryo transfer (FET). While the artificial-FET cycle provides advantages in scheduling and implantation, it falls short in ensuring optimal obstetric outcomes. In contrast, natural-FET ensures embryo implantation conditions if ovulation is correctly identified. Supplementing with exogenous progesterone shields against low corpus luteum progesterone secretion, crucial for positive obstetric outcomes. In mNC-FET, ovulation is hCG-triggered, closely resembling natural cycles and reducing monitoring visits for enhanced patient convenience.Letrozole is a recommended option for anovulatory patients, preserving endometrial thickness. It is cost-effective, less likely to induce multifollicular development than gonadotropins, and better tolerated.In a novel approach, the natural-proliferative-phase-FET initiates progesterone in an unmediated ovulatory cycle at 7 mm endometrial thickness, combining the benefits of a natural proliferative endometrium with the convenience of scheduled artificial cycles. The artificial cycle offers scheduling advantages, but may compromise obstetric outcomes. Natural FET relies on accurate ovulation timing for successful implantation. mNC-FET simplifies the process using hCG induction, minimizing clinic visits for improved convenience. Letrozole is highlighted as a cost-effective and well tolerated option in anovulatory patients. A recent innovative approach combines elements of natural and artificial cycles, showing promise for FET procedures.

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.

Dinâmica folicular em ovelhas leiteiras dentro e fora da estação reprodutiva, empregando alta ou baixa concentração de progesterona na sincronização do clico estral

Abstract Follicular dynamics in dairy sheep is poorly understood. This study assessed the follicular dynamics of dairy sheep within and out of the breeding season by observing the effect of two progesterone concentrations (60 and 120 mg) used in vaginal pessaries in pre-synchronization. The experiment was conducted in April/May and October/November using 40 healthy multiparous dairy ewes predominantly of the Lacaune breed, which underwent daily transrectal ultrasound examinations. The number of ovulations (1.35 vs 1.05), ovulatory follicle diameter (mm) (5.97 vs 5.05), length of the luteal phase (11 vs 9.14 days), and length of the estrous cycle (16.83 vs 16.6 days) were assessed within and out of the breeding season, respectively. The sheep out of the breeding season did not present a corpus luteum at the time of insertion of the vaginal pessary, characterizing anestrus. The ovulatory follicle had a larger diameter in the breeding season even with the shorter length of the follicular phase, suggesting higher viability and quality of the ovulated oocyte. The application of exogenous progesterone extends the luteal phase in the breeding season (11 vs 9.14 days). The anestrus observed out of season suggests the need for a higher progesterone concentration in reproductive protocols. Therefore, breeding protocols can be adapted for different seasons, suggesting the use of vaginal pessaries with a higher progesterone concentration (120 mg) out of the breeding season. The data allowed the characterization of follicular dynamics in dairy sheep, demonstrating their differences in each season based on the use of different progesterone doses in pre-synchronization.

Luteal phase support in assisted reproductive technology.

Infertility affects one in six couples, with in vitro fertilization (IVF) offering many the chance of conception. Compared to the solitary oocyte produced during the natural menstrual cycle, the supraphysiological ovarian stimulation needed to produce multiple oocytes during IVF results in a dysfunctional luteal phase that can be insufficient to support implantation and maintain pregnancy. Consequently, hormonal supplementation with luteal phase support, principally exogenous progesterone, is used to optimize pregnancy rates; however, luteal phase support remains largely 'black-box' with insufficient clarity regarding the optimal timing, dosing, route and duration of treatment. Herein, we review the evidence on luteal phase support and highlight remaining uncertainties and future research directions. Specifically, we outline the physiological luteal phase, which is regulated by progesterone from the corpus luteum, and evaluate how it is altered by the supraphysiological ovarian stimulation used during IVF. Additionally, we describe the effects of the hormonal triggers used to mature oocytes on the degree of luteal phase support required. We explain the histological transformation of the endometrium during the luteal phase and evaluate markers of endometrial receptivity that attempt to identify the 'window of implantation'. We also cover progesterone receptor signalling, circulating progesterone levels associated with implantation, and the pharmacokinetics of available progesterone formulations to inform the design of luteal phase support regimens.

Progesterone-primed cycles result in slower embryos without compromising implantation potential and with the advantages of oral administration and potential cost reduction

To study the impact of the use of progesterone on embryo morphokinetics and on the outcomes of intracytoplasmic sperm injection cycles. Cohort study. Private university-affiliated invitro fertilization center. This study included 236 freeze-all intracytoplasmic sperm injection cycles and the resultant 2,768 injected oocytes cultured in a time-lapse imaging incubation system. Patients were matched by age and divided into groups depending on the protocol used to prevent the luteinizing hormone surge: progestin-primed (144 cycles and 1,360 embryos) and gonadotropin hormone-releasing hormone (GnRH) antagonist (144 cycles and 1,408 embryos) groups. The kinetic recorded markers were time to pronuclear appearance and fading, time to 2-8 cells, time to morulation, time to start of blastulation, and time to blastulation. The durations of cell cycles and time to complete synchronous divisions were calculated. The Known Implantation Data Score ranking was recorded. Morphokinetics and clinical outcomes were compared between the groups. Embryo morphokinetics and clinical outcomes. Slower time to pronuclear appearance, time to 2 cells, time to 7 cells, time to start of blastulation, and time to blastulation were observed in embryos derived from progestin-primed cycles than in those from the GnRH antagonist group. No significant differences were noted in any other morphokinetic milestone. Significantly higher cancellation and implantation rates were observed in the progestin-primed group. However, no significant differences were noted in the pregnancy and miscarriage rates. The expenses for treatment using premature GnRH antagonist and progestins were US$318.18 and US$11.05, respectively. Exogenous progesterone replaces the GnRH antagonist for the prevention of premature luteinizing hormone surge, in freeze-all cycles, with the advantage of oral administration and potential cost reduction.

The adenomyosis/endometriosis IVF patient – call for clinical focus

Endometriosis and adenomyosis are distinct clinical conditions that carry the same pathophysiological features. In recent years the clinical focus on assisted reproductive technology patients with either condition (E/A) has increased, in the recognition that this subgroup of patients might need special attention to obtain reproductive success. Endometriosis and adenomyosis are characterized by a disruption of progesterone and oestrogen signalling pathways, resulting in local oestrogen dominance and progesterone resistance at the receptor level. Recent scientific evidence suggests that the endometrial progesterone receptor resistance encountered in E/A patients can be overcome by a freeze-all policy, followed by down-regulating circulating oestradiol concentrations prior to frozen embryo transfer (FET), in combination with an increase in exogenous luteal phase progesterone supplementation in hormonal replacement therapy (HRT) FET cycles. Specifically, for adenomyosis patients who do not respond to gonadotrophin-releasing hormone agonist down-regulation in terms of a decrease in circulating oestradiol concentrations, a small case series has suggested that the addition of an aromatase inhibitor for 21 days prior to HRT–FET is a valid option. Endometriosis and adenomyosis are hormonally active diseases, which need to be treated by controlling local hyperoestrogenism and progesterone resistance. Based on physiology and recent preliminary clinical data, the authors of this opinion paper wish to stimulate discussion and spark interest in research in E/A patients.

Prenatal Progesterone Treatment Induces Sex-dependent Anxiety and Depressive-like Behaviour in Adult Offspring

Exogenous treatment during pregnancy with steroid hormones (estrogens, androgens, or glucocorticoids) affects the development of the fetus and the sexually mature generation. In clinical practice, the hormone progesterone is used therapeutically in programmes for assisted reproduction, infertility treatment, threatened abortion and premature birth. The hormone has a key role in establishing and maintaining pregnancy through its endocrine and immunological effects. Despite the fact that progesterone is widely used during pregnancy, the long-term effects of fetal exposure to exogenous progesterone on child development have barely been investigated. The aim of the present study is to investigate sex-dependent changes in the emotional status of a generation of prenatally treated with progesterone offspring. Female pregnant rats were treated subcutaneously with progesterone (50 mg/kg) from gestational (G) period G0 to G10. Anxiety and depressive-like behaviour of male and female adult offspring were evaluated with an open field (OF) test, elevated plus maze test (EPM), light dark test (LDT), sucrose preference test (SPT) and forced swimming test (FST). Prenatal treated with progesterone male and female offspring exhibited lower horizontal and vertical activity compared to the male and female control rats in the open field test and decreased distance and time spent in the open arms compared to the matched controls in the EPM test. They demonstrated depressive-like responses with anhedonia in the SPT and increased immobility time in the FST compared to the matched controls. Prenatal treatment with progesterone significantly affected emergence latency, time spent and crossing to the lit compartment in LDT. In conclusion, our results suggest that prenatal treatment with 50 mg/kg progesterone exerts a detrimental effect on emotional behaviour in male and female offspring. Future studies are needed to ascertain the underlying mechanism associated with these sustained behavioural abnormalities due to prenatal hormonal treatment.

The effects of gonadal hormones on heroin Self-Administration in male gonadectomized rats.

Previous studies have shown that gonadal hormones influence opioid self-administration in female rodents, but very few studies have examined these effects in male rodents. The purpose of this study was to examine the effects of chronic hormone treatment on intravenous heroin self-administration in gonadectomized male rats using both physiological and supraphysiological doses of testosterone, estradiol, or progesterone. Gonadectomized male rats were surgically implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement.Using a between-subjects design, rats were treated daily with testosterone (0.175 or 1.75mg, sc), estradiol (0.0005 or 0.005mg, sc), progesterone, (0.0125 or 0.125mg, sc), or their vehicles. After 14days of chronic treatment, a dose-effect curve was determined for heroin (0.0003-0.03mg/kg/infusion) over the course of one week. Neither testosterone nor estradiol altered responding maintained by heroin. In contrast, the high dose of progesterone (0.125mg) reduced responding maintained by all doses of heroin to saline-control levels. This dose of progesterone did not reduce responding maintained by food on a progressive ratio schedule in either food-restricted or food-sated rats. These data indicate that exogenous progesterone or a pharmacologically active metabolite selectively decreases heroin intake in male rodents, which may have therapeutic implications for men with opioid use disorder.

Association of Systemic Hormonal Contraceptives With Reconstruction Procedures for Patellar Instability.

Previous research suggests that estrogen plays a role in increased ligamentous laxity observed within the female population. Whereas many studies have sought to evaluate the impact of exogenous estrogen on anterior cruciate ligament injuries, research has not yet explored its impact on the medial patellofemoral ligament. Furthermore, less is known about the role of exogenous progesterone on ligamentous structures. To determine whether women prescribed systemic estrogen (ethinyl estradiol) or progesterone (norgestimate or etonogestrel) hormonal contraceptives had an increased risk of undergoing reconstruction surgery for patellar instability compared with women without a prescription for systemic hormonal contraceptives. Cross-sectional study; Level of evidence, 3. The TriNetX Research Network database was queried using International Classification of Disease and Common Procedural Terminology codes for women aged 15 to 26 years who underwent reconstruction procedures for patellar instability between 2012 and 2022. Women were grouped according to whether they had a coded prescription for a systemic hormonal contraceptive containing either ethinyl estradiol or etonogestrel; controls were matched by age, sex, race, and ethnicity. The relative risk (RR) of undergoing reconstruction for patellar instability was determined for each contraceptive. After 1-to-1 propensity score matching, 0.054% (525/980,878) of women prescribed a systemic contraceptive containing ethinyl estradiol underwent reconstruction procedures for patellar instability compared with 0.043% (417/980,878) of controls (RR, 1.3; 95% CI, 1.1-1.4; P = .0004). Likewise, 0.058% (67/116,260) of women prescribed a form of systemic contraceptive containing only etonogestrel underwent reconstruction procedures for patellar instability compared with 0.026% (30/116,260) of controls (RR, 2.2; 95% CI, 1.5-3.4; P = .0002). Female patients prescribed systemic contraceptives containing estrogen or progesterone had an increased rate of reconstruction procedures for patellar instability.

Consistency of endometrial receptivity array and histologic dating of spatially distinct endometrial samplings: a prospective, blinded study

To compare the consistency of endometrial receptivity array (ERA) and histologic dating among 3 spatially distinct endometrial samples obtained during a cycle of exogenous estrogen and progesterone. Prospective blinded study. University practice. Twelve patients undergoing a mock frozen embryo transfer cycle. Endometrial biopsy was performed in a manner that provided a spatially organized endometrial specimen, corresponding to the fundus, middle, and lower segment. Each of these 3 sections was further divided into immediately adjacent specimens for ERA and histology. Consistency of the ERA and histology results among fundal, mid, and lower endometrial biopsy specimens. The ERA showed variability in outcome among different patients but dated all specimens originating from the same patient identically. Histologic dating showed variability between patients as well as between different locations within the uterus. When comparing average dating results for each patient, we saw a positive correlation between histologic and ERA dating (Spearman Rho= 0.45); however, this did not reach statistical significance. The ERA results from upper, mid, and lower uterine biopsy specimens were identical for each autologous biopsy, whereas histologic dating showed variability with an average standard deviation of 0.71days. The increased heterogeneity of histologic dating is likely to be attributed to the subjectivity of the test. Furthermore, we did not observe a consistent lag or advancement in histologic or ERA dating between the fundal or lower uterine biopsies. Overall, cliniciansshould be reassured that endometrial tissue will return consistent ERA results independent of the location within the uterus in which it was obtained.

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 &amp;gt; 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.

Lempeng Desidua pada Kecurigaan Kehamilan Ektopik : Sebuah Laporan Kasus

Background: The decidual cast represents a condition which the entire endometrial lining is shed in intact condition through the vagina. This phenomenon is infrequent and has been linked to various factors, including ectopic pregnancy and the use of exogenous progesterone. In the current report, we present a case finding of ectopic pregnancy upon discovery of decidual cast.Case: Female, 36 years old, came with complaints of pain in the pelvic area accompanied by patches of bleeding from the genitals since 1 week ago. On the 8th day since the complaint was felt, the patient complained of severe pain accompanied by discharge of tissue from the genitals. On histopathological examination of the tissue, a decidual cast was found in the absence of chorionic villi. The pregnancy test was positive and on ultrasound examination we found a mass with a cavity measuring 1.55 x 1.53 cm in the left fallopian tube so that the diagnosis of tubal ectopic pregnancy was established and a laparoscopic procedure was carried out. Discussion: The decidual cast is a proliferation of the endometrial lining that is released through the vagina in an intact form. This finding of decidual cast is often found in ectopic pregnancies and is associated with exposure to exogenous progesterone. The release of the decidual cast through the undilated cervix will cause severe pain referred to as membranous dysmenorrhea. The differential diagnosis of this decidual cast finding is the occurrence of abortion. However, the results of histopathological examination of the tissue obtained a decidual cast without chorionic villi so that the possibility of abortion can be removed.Conclusion: The identification of a decidual cast is frequently linked to the occurrence of an ectopic pregnancy. Therefore, its presence should alert clinicians to consider the possibility of an ectopic pregnancy and conduct further investigations.