Hormone Agonist Research Articles

Abstract PS9-48: Depression, sexual dysfunction and quality of life among breast cancer patients with ovarian function suppression: A cross sectional study between ovarian ablation verse GnRH agonists

Abstract Background: Ovarian function suppression is being widely utilized as endocrine therapy to reduce estrogen release in premenopausal breast cancer patients and was achieved either by medical treatment with the Gonadotropin releasing hormone (GnRH) agonist or bilateral oophorectomy. This study aimed to examine the difference between GnRHa and ovarian ablation on depression, sexual dysfunction and quality of life.Methods: The premenopausal breast cancer patients who received ovarian function suppression were enrolled from seven hospital between June 2019 and February 2020. Our independent variable was the type of ovarian suppression, categorized as Ovarian Ablation (OA cohort, n=62) and medical GnRH agonist (GnRHa cohort, n=260). The self-administered questionnaire (OFS-Q5) developed and used in this study aimed to assess the depression (PHQ-9), sexual dysfunction (FSFI) and quality of life (EORTC QLQ-BR23), as well as the contributing factors.Results: In this cross-sectional study, 322 patients with ovarian function suppression completed surveys were collected. The mean sum score of the PHQ-9 in GnRHa cohort tend to be lower than that in ovarian ablation (OA) cohort (9.6 ±5.2 vs. 11.0 ±5.8, OR=1.495, P=0.080). Patients with major depression (PHQ-9≧15) was indicated significantly fewer in GnRHa cohort. Less patients met the criteria for sexual dysfunction (66.1%, FSFI< 26.55) in OA cohort compared with 81.5% of patients with GnRHa (P = 0.008). The ratio of sexual dysfunction remained lower for ovarian ablation women in long-term ovarian suppression (duration of ovarian suppression > 2 years: OA vs GnRHa, 36.7% vs 78.4%, P=2.4E-05). The differences of most subscales of QLQ-BR23 were insignificant in both cohorts.Conclusions: Our finding demonstrate here for the first time that ovarian ablation resulted in worse depression, favour sexual function than those with medical GnRHa, with similar quality of life. More attention need to paid on adverse effect in patients with diverse ovarian function suppression. Citation Format: Junnnan Xu, Tao Sun. Depression, sexual dysfunction and quality of life among breast cancer patients with ovarian function suppression: A cross sectional study between ovarian ablation verse GnRH agonists [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-48.

Immuno-hormonal network in postmenopausal women: disturbance in breast cancer patients.

IntroductionAntibodies to estradiol and progesterone (Es and Pg) modulated their blood serum concentration and biological effects in immunized animals. Antibodies to membrane steroid receptors acted as hormone agonists or antagonists in cell cultures.Material and methodsHere we studied the levels of Es and Pg, idiotypic immunoglobulin (Ig) A1 and anti-idiotypic IgG2 specific to Es and Pg in the serum of postmenopausal women (82 healthy donors and 443 breast cancer patients).ResultsIt was found that individual high ratios of Pg/Es (> 4), IgA-Pg1/IgA-Es1 (> 1) and IgG-Pg2/IgG-Es2 (> 1) were associated with low breast cancer risk (OR = 0.4-0.5). High ratios of IgA-Pg1/IgA-Es1 and IgG-Pg2/IgG-Es2 were associated with a high Pg/Es ratio in healthy women but not in breast cancer patients. The levels of idiotypic IgA to benzo[a]pyrene correlated significantly with IgA-Es1 and IgA-Pg1 levels in both compared groups. IgA-Pg1/IgA-Es1 ratio correlated with IgG-Pg2/IgG-Es2 only in healthy women but not in breast cancer patients.ConclusionsThe normal immune-hormonal balance supports the real adaptation of the organism to environmental carcinogens and inhibits the initiation and promotion of carcinogenesis. The disturbance between certain elements of this network (immune-hormonal disbalance) could stimulate carcinogenesis. Further studies of immune-hormonal interaction could be helpful for understanding the pathogenesis of other carcinogen-induced steroid-dependent diseases in humans.

Angiogenic cytokine and interleukin 8 levels in early luteal phase after triggering ovulation with gonadotropin-releasing hormone agonist in high-responder patients.

Interleukin 8 (IL-8), vascular endothelial growth factor A (VEGFA), its receptors 1 (VEGFR1) and 2 (VEGFR2) are associated with ovarian hyperstimulation syndrome (OHSS) pathophysiological mechanisms. The aim of this study was to evaluate the concentrations of these cytokines depending on the way of ovulation triggering. A total of 51 high-responder patients underwent IVF program and received gonadotropin-releasing hormone agonists (GnRHa) trigger+1500IU human chorionic gonadotropin (hCG) support on the oocyte pick-up (OPU) day (group I), dual trigger (GnRHa+1500IU hCG; group II), or hCG trigger 10,000IU (group III) for the final oocyte maturation. The concentrations of cytokines were evaluated in serum by the enzyme-linked immunosorbent assay kit. VEGFR2 levels were significantly lower in groups I and II than in group III in serum on the OPU (I vs. III, p=.0456; II vs. III, p=.0122) and OPU+5day (I vs. III, p=.0004; II vs. III, p=.0082). VEGFAlevels were lower in group I than in group III (p=.0298) on the OPU day, however, were similar in all groups on the OPU+5day. A small dose of hCG elicits similar concentrations of VEGFA to a full dose of hCG; however, GnRHa triggering reduces the concentrations of VEGFR2, which could lead to the OHSS prevention.

Premenstrual Syndrome

Premenstrual syndrome (PMS) is a recurrent constellation of affective and physical symptoms that begin during the luteal phase of the menstrual cycle and resolve completely or almost completely during the follicular phase. Symptoms range in severity from mild to severe. The pathophysiology of PMS is discussed in this chapter, and potential causes are listed in a table. The diagnosis and differential diagnosis are reviewed. To warrant medical attention, evaluation, and intervention, premenstrual symptoms must be recurrent and sufficiently severe to interfere with daily work and social activities. Mild cases of PMS can be treated with lifestyle modification (e.g., good sleep patterns, regular exercise) and nonpharmacologic therapy (e.g., bright-light therapy, stress management, behavioral therapy). More severe cases warrant aggressive intervention, with pharmacologic therapy and even surgery in women who respond very well to a gonadotropin-releasing hormone (GnRH) agonist and have completed childbearing. This review contains 1 figure, 5 tables and 51 references Key Words: Premenstrual syndrome, premenstrual dysphoric disorder, selective serotonin reuptake inhibitors, anxiogenic progesterone metabolites, estrogen, progesterone.

Premenstrual Syndrome

Premenstrual syndrome (PMS) is a recurrent constellation of affective and physical symptoms that begin during the luteal phase of the menstrual cycle and resolve completely or almost completely during the follicular phase. Symptoms range in severity from mild to severe. The pathophysiology of PMS is discussed in this chapter, and potential causes are listed in a table. The diagnosis and differential diagnosis are reviewed. To warrant medical attention, evaluation, and intervention, premenstrual symptoms must be recurrent and sufficiently severe to interfere with daily work and social activities. Mild cases of PMS can be treated with lifestyle modification (e.g., good sleep patterns, regular exercise) and nonpharmacologic therapy (e.g., bright-light therapy, stress management, behavioral therapy). More severe cases warrant aggressive intervention, with pharmacologic therapy and even surgery in women who respond very well to a gonadotropin-releasing hormone (GnRH) agonist and have completed childbearing. This review contains 1 figure, 5 tables and 51 references Key Words: Premenstrual syndrome, premenstrual dysphoric disorder, selective serotonin reuptake inhibitors, anxiogenic progesterone metabolites, estrogen, progesterone.

Premenstrual Syndrome

Premenstrual syndrome (PMS) is a recurrent constellation of affective and physical symptoms that begin during the luteal phase of the menstrual cycle and resolve completely or almost completely during the follicular phase. Symptoms range in severity from mild to severe. The pathophysiology of PMS is discussed in this chapter, and potential causes are listed in a table. The diagnosis and differential diagnosis are reviewed. To warrant medical attention, evaluation, and intervention, premenstrual symptoms must be recurrent and sufficiently severe to interfere with daily work and social activities. Mild cases of PMS can be treated with lifestyle modification (e.g., good sleep patterns, regular exercise) and nonpharmacologic therapy (e.g., bright-light therapy, stress management, behavioral therapy). More severe cases warrant aggressive intervention, with pharmacologic therapy and even surgery in women who respond very well to a gonadotropin-releasing hormone (GnRH) agonist and have completed childbearing. This review contains 1 figure, 5 tables and 51 references Key Words: Premenstrual syndrome, premenstrual dysphoric disorder, selective serotonin reuptake inhibitors, anxiogenic progesterone metabolites, estrogen, progesterone.

Abstract 17016: Cardiovascular Safety Profile of Gonadotropin Releasing Hormone (GnRH) Antagonist Compared to GnRH Agonist Among Patients With Prostate Cancer: A Meta-Analysis

Introduction: Androgen deprivation therapy (ADT) is the cornerstone of advanced prostate cancer therapy. The degree that ADT contributes to cardiovascular disease remains uncertain with conflicting studies. ADT can be achieved through the use of gonadotrophin releasing (GnRH) hormone agonist or, more recently, GnRH antagonists. The objective of this study was to determine whether cardiovascular events differ after the initiation of GnRH agonist compared with GnRH antagonist in randomized control trials. Methods: From PubMed, Cochrane Central, and Embase we identified all randomized studies comparing GnRH antagonists with GnRH agonists in patients with prostate cancer from 2000-2020. Outcomes studied included major adverse cardiovascular events (MACE), coronary artery disease (CAD), cerebrovascular accidents (CVA), atrial fibrillation (AF), and heart failure (HF). A random effects model using the Mantel-Haenszel method was used to assess outcomes. Results: Overall, we identified 7 studies (n = 3298) which reported outcomes in prostate cancer patients receiving GnRH antagonists (n = 2127) compared with those receiving GnRH agonists (n = 1171). When compared to men receiving GnRH agonists, the incidence of MACE (RR 0.52, 95% CI 0.35-0.76, p<0.001) and CAD (RR 0.46, 95% CI 0.27 - 0.77, p=0.004) was lower in men receiving GnRH antagonists. There was no difference in the rates of CVA (RR 0.93, 95% CI 0.31-2.77, p=0.89), AF (RR 0.49, 95% CI 0.09-2.72, p=0.41), or HF (RR 0.55, 95% CI 0.19-1.59, p=0.52) between the two groups. Conclusion: For men with prostate cancer receiving ADT, GnRH antagonists decreased the incidence of MACE and coronary artery disease by half compared to men treated with GnRH agonists. GnRH antagonists have a more favorable cardiovascular safety profile than GnRH agonists.

Abstract 15754: Coronary Calcification is Associated With Prior GnRH Agonist Therapy in Men With Recurrent Prostate Cancer Undergoing PET/CT Imaging

Background: Gonadotropin releasing hormone (GnRH) agonist therapy is associated with major adverse cardiovascular (CV) events in men with prostate cancer. The effect of GnRH agonists on vascular calcification is not known. Methods: Consecutive patients who underwent 18F-fluciclovine positron emission tomography (PET) /computed tomography (CT) at our institution for recurrent prostate cancer were retrospectively identified. Clinical and demographic data were obtained from the medical record. Patients without available data on prior prostate cancer therapies received were excluded (n=25). Coronary calcification was qualitatively assessed on non-gated CT scans using a published scoring system. The association of prior GnRH agonist therapy with coronary calcification was evaluated using stratified odds ratio (OR) analysis in a 2x2 contingency table. Results: Among 186 men included, median age was 69.0 years (IQR 64.3, 74.5) and CV comorbidities were common (72% hypertension, 68% hyperlipidemia, 43% current or former smoking, and 21% diabetes mellitus). 55 patients (30%) received prior hormone therapy, 50 of whom received a GnRH agonist either as single- or multi-agent therapy. Men with prior GnRH agonists were older than those without prior GnRH agonists (71.4 vs. 68.4 years, p=0.025). There were no significant differences in prevalence of CV comorbidities between the two groups. Men with at least mild coronary calcification were more likely to have received prior GnRH agonist therapy (OR=3.0, 95% CI 1.2-7.1, p=0.015 by Fisher’s exact test), with a stronger association seen in younger men (OR=3.9, age <69 years) than in older men (OR=1.8, age ≥69). Conclusions: Coronary calcification is associated with prior GnRH agonist therapy in men with recurrent prostate cancer undergoing PET/CT imaging. The utility of vascular protective therapies including aspirin and statin to mitigate the adverse CV effects of GnRH agonists requires further study.

Abstract 14603: Arterial Vascular Events in Men With Prostate Cancer Receiving Hormone Therapy: An Analysis of the FDA Adverse Event Reporting System (FAERS)

Introduction: Hormone therapy has been associated with adverse cardiovascular events including arterial vascular events in men with prostate cancer. It is unclear if the risk of arterial vascular events varies by type of hormone therapy used. Methods: The Food and Drug Administration’s Adverse Event Reporting System (FAERS) was used to compare arterial vascular event reporting in men receiving hormone therapy from 01/01/2000 to 04/30/2020 for prostate cancer. Therapies evaluated were gonadotrophin-releasing hormone (GnRH) agonists (i.e. leuprolide), GnRH antagonists (i.e. degarelix), androgen receptor (AR) antagonists (i.e. bicalutamide) and abiraterone. Arterial vascular events included coronary artery disease, myocardial infarction, ischemic stroke, peripheral vascular disease, and hypertension requiring hospitalization. Polytomous logistic regression (adjusted for age, need for hospitalization, and event reporting source) was performed for non-GnRH agonists as compared to GnRH agonists. Results: Among 34,466 events reported during the study period on single agent therapy, 10.6% were arterial vascular events (5.9% hypertension requiring hospitalization, 2.3% coronary artery disease or myocardial infarction, 2.1% ischemic stroke, and 0.3% peripheral vascular disease). Median age of those with reported arterial vascular events was 76 years (IQR 70 - 82). Arterial vascular events were reported less commonly in men receiving AR antagonists (adjusted reporting odds ratio [ROR] 0.7 [95% CI 0.7-0.8], p<0.0001), abiraterone (ROR 0.9 [0.8-0.98], p=0.02), and GnRH antagonists (ROR 0.9 [0.7-1.1], p=0.15) as compared to those receiving GnRH agonists. Conclusion: Arterial vascular events are reported more commonly in men receiving GnRH agonists for prostate cancer as compared with other types of hormone monotherapy. Use of non-GnRH agonists may reduce the risk of adverse cardiovascular events on hormone therapy in men with prostate cancer.

Identification of drivers of breast cancer invasion by secretome analysis: insight into CTGF signaling

An altered consistency of tumor microenvironment facilitates the progression of the tumor towards metastasis. Here we combine data from secretome and proteome analysis using mass spectrometry with microarray data from mesenchymal transformed breast cancer cells (MCF-7-EMT) to elucidate the drivers of epithelial-mesenchymal transition (EMT) and cell invasion. Suppression of connective tissue growth factor (CTGF) reduced invasion in 2D and 3D invasion assays and expression of transforming growth factor-beta-induced protein ig-h3 (TGFBI), Zinc finger E-box-binding homeobox 1 (ZEB1) and lysyl oxidase (LOX), while the adhesion of cell-extracellular matrix (ECM) in mesenchymal transformed breast cancer cells is increased. In contrast, an enhanced expression of CTGF leads to an increased 3D invasion, expression of fibronectin 1 (FN1), secreted protein acidic and cysteine rich (SPARC) and CD44 and a reduced cell ECM adhesion. Gonadotropin-releasing hormone (GnRH) agonist Triptorelin reduces CTGF expression in a Ras homolog family member A (RhoA)-dependent manner. Our results suggest that CTGF drives breast cancer cell invasion in vitro and therefore could be an attractive therapeutic target for drug development to prevent the spread of breast cancer.

Suppression of ovarian activity in a captive African Lion Panthera leo after deslorelin treatment

Abstract: With the intent to evaluate the efficiency of a contraceptive treatment for cyclic ovarian suppression in African Lionesses Panthera leo using a Gonadotrophin-Releasing Hormone (GnRH) agonist bioimplant, noninvasive fecal steroid assay associated with the observation of the behavioral estrus were employed for a period of 36 months. Five captive adult females, maintained with a vasectomized male, subcutaneously received a 9.4mg deslorelin acetate implant. The treatment initially stimulated behavioral estrus along with ovarian activity, demonstrated by an estrogen increase in two lionesses. A rise in progesterone concentration in two other animals suggested possible treatment-induced ovulation. After the initial period, deslorelin prevented ovarian activity for at least 22 months. Two females exhibited signs of behavioral estrus after 22 and 31 months. A third lioness with an increased estrogen concentration did not exhibit behavioral estrus signs or a consequent progesterone surge until 33 months after implantation, suggesting a possible resumption of ovarian activity. One female did not exhibit any behavioral estrus signs nor a rise in steroid levels after the “treatment-induced” estrus throughout the entire experiment (36 months). One lioness died after 15 months without exhibiting signs of estrus or an increased progesterone level, however, the estrogen concentration increased 12 months post-implantation, suggesting resumed ovarian activity. The study showed that long-term treatment with a GnRH agonist can be extremely effective as a contraceptive treatment in African lionesses, however, the duration of contraception may vary among individuals and may bear the risk of permanent loss of normal ovarian activity.

An Oral Gonadotropin-Releasing Hormone Antagonist for Advanced Prostate Cancer

Injectable depot formulations of luteinizing hormone–releasing hormone (LHRH) agonists are the standard method of attaining androgen deprivation in men

Cardiac and Hepatic miRNAs Altered Expression in Rat Embryo after Bisphenol-A (BPA) Exposure and Their Histopathological Impact (In vivo Study)

Introduction: Plastic compound are widely used in modern life. Bisphenol-A is an essential component in high quality plastic containers such as bottles and food boxes. Beside its hormonal agonist and antagonist effects, Food and drug administration (FDA) had reported it is transmitted from mother to fetus through placental circulation causing mi-RNAs mutation. mi-RNAs regulate cellular morphology and functions through its essential role in genetic expression. The aim of the present study is to investigate the effect of exposure of BPA on maternal [placenta, body weight & blood pressure] and fetal [liver, heart & miRNAs expression] and the impact of miRNAs expression disorders on multiorgan development, namely cardiac and hepatic development.
 Materials and Methods: 60 healthy pregnant females’ rats were picked up since day one of gestation and divided into three groups (n=20). (c) control group gained access to drinking water containing only the vehicle (tween-80) 0.1/ml for three weeks.(10-BPA) group, gained access to drinking water containing 10 mg/L of BPA for three weeks.(20-BPA) group, gained access to drinking water containing 20 mg/L of BPA for three weeks. Placenta, liver and heart samples were collected and histopathological changes were recorded and mi-RNAs expression was investigated.
 Results: Histopathological changes were noticed in BPA related groups if compared to control group. mi-RNAs expression was found in same groups with variable extent. A significant increase was noticed in body weight and blood pressure of pregnant rats.
 Conclusion: Our data examined the impact of BPA exposure on different organs and their related miRNAs expression which showed a non-neglectable effect especially on the placenta of the mother and fetal heart and liver.

Lower odds of cardiac events for gonadotropic releasing hormone antagonists versus agonists.

34 Background: Gonadotropic releasing hormone (GnRH) agonists and antagonists are first-line for advanced prostate cancer, but may be associated with cardiac toxicity. Observational studies show a relatively lower risk for GnRH antagonists, but a randomized trial found no difference. We compared the reporting of cardiac events for GnRH agonists and antagonists. Methods: We used VigiBase, the World Health Organization global database of case safety reports, which collects data from more than 130 countries to extract drug-adverse event (AE) pairs. Using Medical Dictionary for Regulatory Activities terminology, we identified AEs related to GnRH antagonist (degarelix) or agonist (leuprolide, goserelin, triptorelin, histrelin) therapy for prostate cancer, including myocardial infarction, heart failure, cardiomyopathies, new-onset valvular dysfunction, and other major cardiac events. To explore a possible relationship we used the reporting odds ratio (ROR), a surrogate measure of association using all other reactions as non-cases. A lower bound of a 95% confidence interval of ROR > 1 reflects a disproportionality signal that more AEs are observed than expected. Results: We found 10,504 AEs for GnRH agonists, and 1,606 for GnRH antagonists; 805 (7.7%) were cardiac for agonists, and 102 for antagonists (6.4%). We found no signal for overall cardiac events or any subgrouping for GnRH antagonists, but identified a signal both for overall cardiac events (ROR 1.20, 95% CI 1.12-1.29) and myocardial infarction (1.76, 1.57-1.97) for GnRH agonists. Conclusions: Using validated pharmacovigilance methodology, we found a signal for myocardial infarction for GnRH agonists, but did not detect one for GnRH antagonists. As cardiovascular disease is the most common cause of non-cancer death in prostate cancer patients, this finding is of specific relevance in the current era of novel second-line anti-androgen therapies which may compound toxicity when added to first-line therapy. The relative cardiac toxicity of GnRH agonist therapy compared to GnRH antagonists merits renewed attention.

Quality of life of prostate cancer (PCa) patients with testosterone deficiency symptoms (TDS) before initiation of gonadotropin-releasing hormone (GnRH) agonist therapy: Subgroup analysis of EQUINOXE study.

232 Background: Both PCa and TDS risk increase with age. Patients may therefore suffer from both conditions, and their quality of life (QoL) be reduced. Unexpectedly, multivariate analysis of the EQUINOXE study (NCT02630641) identified baseline TDS as a significant factor improving QoL after 6 months of GnRH agonist therapy. We therefore aim to analyze baseline parameters of this subgroup. Methods: EQUINOXE was a French prospective, multicenter, non-interventional study. Urologists recruited partner-patient couples with PCa for whom androgen deprivation therapy (ADT) was indicated. Data were collected at inclusion and after 6 months of treatment, on QoL (WHOQOL-BREF), perception of disease (B-IPQ), symptoms of the disease (QLQ-PR25) and perception of cohesion within the patient-partner relationship (dyadic adjustment, DAS-16). TDSat baseline, determined by QLQ-PR25 “treatment related symptoms” score ≥25/100, was the main parameter identified by multivariate analysis in improvement of QoL (OR [95% CI]: 3.0 [1.46, 6.17]. Post hoc subgroup analysis was made to compare baseline parameters of patients with and without TDS. Results: 487 patients were included in this analysis, 26% of whom had TDS at baseline. Symptoms were (quite a bit or very much): feeling of less masculinity (55.2%), hot flushes (41%), weight gain (40.1%) and enlarged nipples (23.1%). Patients with TDS were slightly older than those without TDS (75.3±8.3vs 73.8±8y.o), had significantly worse performance Status (0-1-2+ in 37.0-45.7-17.3% vs 52.8-36.4-10.8%, p=0.0153) and suffered more frequently from recurrent PCa (35.7% vs 24.7%, p=0.0175). Symptoms other than urinary and sexual (but including asthenia) were more frequent (p=0.0126). All dimensions of WHOQOL-BREF were rated significantly worse. Total score of illness (B-IPQ) was worse: 42.2±8.2 vs39.1±9.4, p=0.0040. Cohesion in the couple (DAS score) was worse: 98.6±22.3 vs107.3±20.9, p=0.0006. Conclusions: Patients with TDS experienced at baseline a worse cohesion of the couple and a lower QoL than patients without TDS but benefited relatively more from ADT in term of QoL. Clinical trial information: NCT02630641.

Treatment-induced changes in levels of brain natriuretic peptide in prostate cancer patients receiving gonadotropin-releasing hormone antagonists or agonists.

Treatment-induced changes in levels of brain natriuretic peptide in prostate cancer patients receiving gonadotropin-releasing hormone antagonists or agonists.

How does long-term gonadotrophin-releasing hormone (GnRH) agonist therapy provided before in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) compare with standard IVF/ICSI alone for women with endometriosis?

How does long-term gonadotrophin-releasing hormone (GnRH) agonist therapy provided before in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) compare with standard IVF/ICSI alone for women with endometriosis?

Ovarian hyperstimulation closely associated with resumption of follicular growth after chemotherapy during tamoxifen treatment in premenopausal women with breast cancer: a multicenter retrospective cohort study

BackgroundWe previously reported that tamoxifen (TAM)-induced ovarian hyperstimulation (OHS) is associated with high serum concentrations of estradiol in premenopausal women with breast cancer. To investigate risk factors for TAM-induced OHS, we performed a retrospective multicenter study.MethodsPremenopausal patients who received surgical therapy for endocrine-dependent breast cancer (n = 235) were recruited in this study and classified into 4 groups: group A, treated with TAM alone; group B, TAM treatment after 2-year-combined therapy with a gonadotropin-releasing hormone (Gn-RH) agonist; group C, TAM treatment after chemotherapy; group D, 5-year-combined therapy with TAM and a Gn-RH agonist. A serum estradiol value of more than 300 pg/mL or mean follicular diameter of more than 30 mm was defined as OHS.ResultsThe incidence of OHS in group A (n = 13/26, 50.0%) was significantly higher than those in group B (n = 17/63, 27.0%), group C (n = 20/110, 18.2%), and group D (n = 0/36, 0%). The incidence of OHS was significantly correlated with aging, and the median serum concentration of estradiol in the presence of OHS was 823.0 pg/mL. The incidence of OHS (less than 47 years old) was 62.5% in group A, 48.6% in group B, and 28.2% in group C, respectively. Notably, the incidence rate of OHS following amenorrhea in group C (n = 13/20, 65.0%) was significantly higher than that in group B (n = 1/17, 5.9%).ConclusionsThese findings indicate that the onset of OHS following amenorrhea was common in the post-chemotherapeutic group, while its ratio was low in the group after Gn-RH analog treatment, suggesting that combined treatment-based management involving TAM therapy is necessary for premenopausal patients with breast cancer.

Elective frozen embryo transfer – What is the evidence?

Fresh embryo transfer (ET) has been the norm in Assisted reproductive technology (ART) treatment. However, there has been a concern about decreased implantation and pregnancy rates due to altered endometrial receptivity, resulting from the supra-physiological hormonal levels associated with controlled ovarian stimulation (COS). Improvement in embryo survival rates with vitrification has led to an increase in the use of elective freezing of all good quality embryos and transfer in subsequent cycles, i.e., elective frozen ET (eFET). The use of gonadotropin-releasing hormone (GnRH) agonist trigger and segmental in vitro fertilization (IVF) to prevent ovarian hyperstimulation syndrome in hyper responders, has further enhanced the use of e FET. Significantly higher pregnancy rates after frozen-thawed ET in some reports have encouraged wider use of elective freeze-all cycles in ART. Recent studies have shown that in patients with regular menstrual cycles, a freeze-all strategy with GnRH agonist triggering did not result in higher on-going pregnancy rates and live birth rates (LBRs) as compared to fresh transfers with the use of human chorionic gonadotropin for the trigger. There have been no studies comparing fresh verses eFET in poor responders. Significant benefit of e FET has been documented only in hyperresponders. Despite the potential advantages, it seems that e FET is not designed for all IVF patients and a careful patient selection is advocated to derive true benefit from this strategy.

Influence of controlled ovarian stimulation protocols on ovarian hyperstimulation syndrome patterns during in vitro fertilization programs

Different protocols of controlled ovarian stimulation have a significant influence on ovarian hyperstimulation syndrome (OHSS) patterns in women who undergo in vitro fertilization programs (IVF).The objective of this research was to evaluate the impact of different ovarian stimulation protocols on various clinical and laboratory parameters of OHSS, such as embryologic characteristics, hormonal changes, hemostasis, and IVF outcomes. The study was made on the basis of the MPUE “Center of Reproductive Medicine” (Minsk, Belarus) and included,in total, 718 women who underwent IVF for infertility treatment. 103 patients developed OHSS and were divided into two groups based on hormonal stimulation protocols: Group 1 included 60 women who were stimulated with gonadotrophin releasing hormone (GnRH) agonists protocol; Group 2 consisted of 43 women who were prescribed GnRH antagonists during ovarian stimulation.In Group 1 (ovarian stimulation protocol with GnRH agonists), we established significantly higher serum concentrations of estradiol and progesterone during IVF and more marked hemostatic shift towards hypercoagulation: statistically significant elevation of fibrinogen and D-dimes simultaneously with decrease in the primary anticoagulants (antithrombin III and protein С) functional activity. Also, Group 1 had a significantly higher incidence of the early form of OHSS and embryo transfer cancellation caused by a high risk of severe OHSS.OHSS that has developed after the GnRH agonists protocol of controlled ovarian stimulation is associated with higher risks of complications and lower chances of successful pregnancy, which is explained by hyperestrogenic state, elevated progesterone levels, marked hypercoagulation, and higher incidence of early OHSS, which leads to the necessity of embryo transfer cancellation.