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PubMed2005

Modulation of estrogen action during preimplantation period and in immature estradiol-primed rat uterus by anti-implantation agent, ormeloxifene.

Studies were undertaken to evaluate the influence of estrogen antagonist-cum anti-implantation agent, ormeloxifene, on 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity and estrogen action in rat uterus during preimplantation period and to examine its ability to induce progesterone receptor (PR) in immature rat model. A group of female rats received orally a contraceptive dose of 1.25 mg/kg of ormeloxifene on Day 1 postcoitum (pc). Rats were sacrificed on Days 3, 4 and 5 pc, and uterine tissues were processed for enzymatic, estrogen receptor and estradiol (E(2)) estimations. Immature ovariectomized rats received ormeloxifene, subcutaneously for 3 days at various doses in the absence or presence of estradiol, and uterine PR levels were measured using (3)H-R5020 as radioligand. Results revealed that ormeloxifene treatment caused a marked increase in enzyme activity of 17beta-HSD on Days 3, 4 and 5 pc as compared to respective controls. Further, total uterine estrogen receptors as estimated by exchange assay showed a noticeable decrease on Days 4 (35%) and 5 (>80%) pc in ormeloxifene-treated groups. The results correlated well with a decrease in tissue E(2) levels. In immature rats, ormeloxifene caused a dose-dependent increase in cytosolic PR levels; ormeloxifene given along with E(2) (0.1 mug) for 3 days caused a significant reduction in concentration of PRs at 10 mug and higher doses. Ormeloxifene also induced (3)H-progesterone (P) uptake by immature rat uterus. However, in the presence of E(2), it significantly reduced (3)H-P uptake. The in vitro competitive binding experiments did not reveal any displacement of (3)H-R5020 either by ormeloxifene or by its hydroxy derivative from PR. The results suggest that in addition to its competitive antagonism at estrogen receptor level, ormeloxifene enhances the inactivation of intracellular E(2) to estrone, a biologically less active form, thus declining estrogen receptor pool. Moreover, it causes indirect anti-progestational effects in the uterus by virtue of its anti-estrogenic profile rather than by blocking the PRs.

17-Hydroxysteroid Dehydrogenases↗

PubMed2022

Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study.

BACKGROUND: Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer. PATIENTS AND METHODS: This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Confirmed partial response (PR) was observed in six patients [ORR = 28.6%; 95% confidence interval (CI) 11.3% to 52.2%] who had received a median of two prior advanced chemotherapy lines. Lurbinectedin was active in both BRCA mutations: four PRs in 11 patients (36.4%) with BRCA2 and two PRs in 10 patients (20.0%) with BRCA1. Median DoR was 8.6 months, median PFS was 4.1 months and median OS was 16.1 months. Stable disease (SD) was observed in 10 patients (47.6%), including 3 with unconfirmed response in a subsequent tumor assessment [ORR unconfirmed = 42.9% (95% CI 21.8% to 66.0%)]. Clinical benefit rate (PR + SD ≥ 4 months) was 76.2% (95% CI 52.8% to 91.8%). No objective response was observed among patients who had received prior poly (ADP-ribose) polymerase inhibitors. The most common treatment-related adverse events (AEs) were nausea (61.9%), fatigue (38.1%) and vomiting (23.8%). These AEs were mostly grade 1/2. The most common grade 3/4 toxicity was neutropenia (42.9%: grade 4, 23.8%: with no febrile neutropenia). CONCLUSIONS: This phase II study met its primary endpoint and showed activity of lurbinectedin in germline BRCA1/2 breast cancer. Lurbinectedin showed a predictable and manageable safety profile. Considering the exploratory aim of this trial as well as previous results in other phase II studies, further development of lurbinectedin in this indication is warranted.

Humans↗

PubMed2006

Current trends in the treatment of infertility in men with spinal cord injury.

OBJECTIVE: To determine current use of penile vibratory stimulation (PVS), electroejaculation (EEJ), and intrauterine insemination (IUI) in treatment of infertility in men with spinal cord injury (SCI). DESIGN: Prospective survey, retrospective chart review, and literature review. SETTING: Major university medical center. PATIENT(S): Male SCI patients and female partners. INTERVENTION(S): A survey administered to professionals determined current treatment methods for infertility in couples with SCI male partners. MAIN OUTCOME MEASURE(S): Sperm retrieval methods, ejaculation success rates, total motile sperm (TMS), IUI application, and IUI outcomes. RESULT(S): Twenty-eight percent of surveyed professionals do not retrieve sperm from ejaculates of SCI patients, relying instead on retrieval from reproductive tissues. Reasons for not offering PVS or EEJ were lack of familiarity, training, or equipment. Thirty-four percent do not offer IUI to these couples. Chart review showed that semen could be retrieved by PVS or EEJ in 95% of patients. Fifty-three percent and 43% of trials had TMS >5 and >10 x 10(6), respectively. Of survey respondents performing IUI, 42% lacked enough data to estimate pregnancy rates (PRs) in these couples. Literature review showed IUI PRs between 9% and 18% per cycle and 30% and 60% per couple. CONCLUSION(S): Based on ejaculation success rates, TMS yields, and IUI outcomes, the methods of PVS, EEJ, and IUI warrant consideration in centers not currently offering these options for couples with SCI male partners.

Comorbidity↗

PubMed2006

Role of gonadotropin-releasing hormone antagonists in poor responders.

OBJECTIVE: To evaluate the role of GnRH antagonists in poor-responder protocols. DESIGN: Literature review. CONCLUSION(S): The optimum stimulation protocol for poor responders is unknown. Although many IVF programs currently use GnRH antagonists for poor responders, there have been only four prospective, randomized trials comparing GnRH antagonists to alternate protocols. None of these studies had sufficient power to evaluate a difference in pregnancy rates (PRs), and in all four cases, IVF outcomes were comparable. Nevertheless, interest in the use of GnRH antagonists in poor responders has continued. GnRH antagonists may be associated with simpler stimulation protocols, lower gonadotropin requirements, reduced patient costs, and shorter downtimes between consecutive cycles. However, the greatest advantage of GnRH antagonists may lie in the ability to assess ovarian reserves immediately prior to deciding whether or not to initiate gonadotropin stimulation. The ability to respond to cycle-to-cycle variation in antral follicle counts may allow the optimization of oocyte yield and reduce cycle cancellation rates. It remains to be seen if this approach (initiating gonadotropins only in cycles where an adequate antral follicle count is present) also translates into higher clinical PRs for poor responders.

Clinical Trials as Topic↗

PubMed2007

Moderately elevated levels of basal follicle-stimulating hormone in young patients predict low ovarian response, but should not be used to disqualify patients from attempting in vitro fertilization.

OBJECTIVE: To evaluate and compare IVF outcomes of patients within different age categories who had a normal basal FSH level with outcomes of patients with an elevated day 3 FSH level. DESIGN: Retrospective analysis. SETTING: Large, private IVF center. PATIENT(S): We analyzed 2,708 patients. Of these, 2,477 had normal basal FSH levels, and 231 had elevated basal FSH levels (> or =13.03 IU/L). Patients were segregated into various age groups. INTERVENTION: Follow-up. MAIN OUTCOME MEASURE(S): Outcomes of IVF overall, including cancellation rates, oocyte yield, and fertilization, implantation, and clinical pregnancy rates (PRs). RESULT(S): Cancellation rates were significantly higher in patients with elevated day 3 FSH levels compared with patients with normal FSH levels in all age groups. A significantly lower oocyte yield was observed in patients with elevated basal FSH. Fertilization rates were not affected by FSH levels. A significant decrease in the number of embryos available for transfer in patients > or =38 with an elevated day 3 FSH level was found. Implantation and clinical PRs were lower in patients >40 years of age who had an elevated day 3 FSH level when compared to same age patients with a normal day 3 FSH level. Loss rates were not significantly different. CONCLUSION(S): Young women with an elevated basal FSH level should be counseled differently than older women, and should be given adequate counseling and granted the opportunity to undergo an IVF cycle.

Adult↗

PubMed2007

Predicting factors for endometrial thickness during treatment with assisted reproductive technology.

OBJECTIVE: To discover the factors contributing to endometrial thickness, and to assess the impact of endometrial thickness on pregnancy rates (PRs) according to these factors. DESIGN: Retrospective study. SETTING: In vitro fertilization unit in a university hospital. PATIENT(S): All women with primary infertility and no previous pregnancies who underwent IVF treatment at the Chaim Sheba Medical Center, Tel Hashomer, Israel, between August 9, 2001-December 31, 2004. INTERVENTION: Measurement of endometrial thickness by the use of transvaginal ultrasound probe on the day that hCG was administered during an IVF cycle. MAIN OUTCOME MEASURE(S): Factors influencing endometrial thickness and the relationship between endometrial thickness and PRs. RESULT(S): The mean endometrial thickness decreased as a function of the patient's age. The thickest endometrium was found in patients <25 years of age (11.9 +/- 2.5 mm), and the thinnest endometrium was found in patients >40 years of age (9.6 +/- 2.3 mm). Other factors, such as E(2) levels, etiology of infertility, induction of ovulation protocol, and type of gonadotropin used, were also found to contribute to endometrial thickness. CONCLUSION(S): Our data support the case for an "aging" of the endometrium. The chances of achieving a thick endometrium for patients >40 years of age are lower than for younger patients. Furthermore, a thicker endometrium is correlated with a higher PR only for patients >35 years of age.

Adult↗

PubMed2006

Mental health nursing students' relationships with the pharmaceutical industry.

INTRODUCTION: The medical profession's relationship with the pharmaceutical industry (PI) has come under increased scrutiny in recent years, however little is known on the subject in mental health nursing. AIMS: The study sought to investigate: (1) the frequency of contact between mental health nursing students and PI employees; (2) students' attitudes and beliefs about their relationship with the PI; (3) the range of 'gifts', promotional items and hospitality accepted or seen in clinical environments by students in a one year period; and (4) students' attitudes to 'gifts', promotional items and hospitality offered by the industry. METHOD: Employing a survey design, a 35-item questionnaire was distributed to 472 students at two universities in the UK. Data were analysed from 347 respondents by means of descriptive statistics and simple content analysis. RESULTS: The findings suggest that students have significant contact with the industry through one-to-one meetings with pharmaceutical representatives (PRs) and by attending events giving information on specific drugs or general mental health issues. Students also identified a number of benefits (e.g. receiving "up-to-date" information on new drugs) and problems (e.g. the potential influence exerted on practitioners to use their drugs) arising out of this contact. Most students (79.8%) had accepted some form of 'gift' from the industry but few (11.5%) believed it was unacceptable to do so. The presence of promotional items in the clinical environment was seen as advertising (84.4%) but few students (19.3%) believed clinical environment should be free of these items. Over half (57.1%) of the students believed that PRs did not always give unbiased information but thought that they and mental health nurses in general would be able to detect any bias. CONCLUSIONS: In parallel with medicine, the study has shown that the pharmaceutical industry has at least the potential to influence mental health nursing students. Within medicine this realisation has triggered a vigorous debate on how medical schools should respond to the promotional activities of the PI. We suggest this study goes some way to demonstrating there is a need for these issues to be debated in the education of mental health nurses.

Attitude of Health Personnel↗

PubMed2026

Pharmacogenomics of antipsychotic-induced weight gain: A systematic review.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) is a major clinical concern, affecting approximately 30% of patients. Clinical predictors explain only part of AIWG risk. Genetic and molecular variations are hypothesized to contribute to susceptibility. The purpose of this review is to summarize recent results to identify replicated and novel findings. STUDY DESIGN: Applying PRISMA guidelines, we searched MEDLINE, Embase, and PsycINFO (May 2018-May 2026) for studies on genetic and molecular associations with AIWG, extending our prior review. Reviews, editorials, and conference abstracts were excluded. We extracted study characteristics (design, diagnosis, antipsychotic exposure, sample size, ancestry, genetic variants, and AIWG outcomes) (e.g., ≥7% weight gain, BMI change). RESULTS: Fifty-three studies met inclusion criteria. In candidate gene studies, the most consistently replicated genes associated with AIWG were observed for DRD2, HTR2C, and MC4R. Multiple novel associations were identified by genome-wide association studies (GWAS) (e.g., MAP2K1, ZDBF2, PEPD), polygenic risk scores (PRS) (e.g., body mass index PRS), gene expression (e.g., CYP3A4, EP300), and epigenetic analyses (e.g., cg12034943 at CRTC1). CONCLUSIONS: Polymorphisms in candidate genes related to neurotransmission and appetite regulation continue to be investigated for associations with AIWG, while novel findings have emerged from GWAS, gene expression, and epigenetic studies. Evidence remains inconsistent due to limited replication, methodological variability, sparse ancestry data, and geographical underrepresentation. No single genetic variant is ready for clinical use, and multi-omic and multi-ancestry models are needed to improve prediction and clinical utility.

Humans↗

PubMed2026

Genetic evidence for causality of late chronotype on metabolic syndrome in East Asians and Europeans.

CONTEXT: The impact of chronotype-defined as an individuals' inherent preference of sleep timing-and its genetic determinants on metabolic syndrome (MetS) has been less studied. OBJECTIVE: This study investigated the causal relationship between late chronotype and MetS using Mendelian randomization (MR) analysis, based on data from the Taiwan Biobank (TWB) and parallel analyses in the UK Biobank (UKB). METHODS: A total of 36,845 participants from TWB served as the discovery cohort, and 235,639 participants from UKB served as the replication cohort. Late chronotype was defined in TWB as a preference for bedtime after midnight, and in UKB as self-report as being an 'evening' person. The association between late chronotype and MetS, along with its components, was evaluated in TWB, and validated in UKB. Genome-wide association analyses for late chronotype were first conducted in TWB and then meta-analyzed with UKB. Polygenic risk scores (PRS) for late chronotype were constructed and tested for association with MetS. Causality between late chronotype and MetS was examined using one-sample MR analysis in TWB and validated in UKB. RESULTS: Late chronotype was significantly associated with MetS, as well as with central obesity, hyperglycemia, and hypertriglyceridemia, in both TWB and UKB (all P < 0.0083, considering Bonferroni correction). The constructed PRS of late chronotype also showed significant associations with MetS and several of its components (several P < 0.0083, considering Bonferroni correction). Findings from the one-sample MR analysis indicated a potential causal effect of late chronotype on MetS. CONCLUSIONS: This study provides evidence of a robust association between late chronotype and MetS across populations of diverse ancestry, including Taiwanese and European.

Humans↗

PubMed2003

Cyclosporine A toxicity in association with reduced renal mass.

The long-term effect of cyclosporine A (CsA) in male Wistar rats with reduced renal mass was studied. The aim of the study was to highlight the relationship of CsA effect on rats, simulating patients with two functioning kidneys (eg, heart, liver transplant recipients) and one kidney (renal transplant recipients). The Wistar rats were subjected to unilateral nephrectomy (Unx, n = 14) and to 5/6 nephrectomy (STnx, n = 14). Half of these rats and half of the sham operated ones (control, n = 13) were administered CsA (10 mg/kg/d) for 28 days IP. The serum creatinine (S(CR)), total protein (S(P)), and urine protein (U(P)) values as well as the whole blood CsA levels were determined on the 28th day of the study. The remnant kidneys were evaluated by image analyses and semiquantitative methods after sacrifice on the 28th day. In the three non-CsA-treated groups (Unx, STnx, and control) S(CR) was significantly higher in STnx rats than in Unx rats (P =.011). Percent of renal scarring (PRS) was significantly higher in Unx (P =.02) and in STnx rats (P =.017), compared with the control group. Among CsA-treated three groups S(CR) was significantly higher in STnx rats compared with Unx (P =.017). In addition, segmental sclerosis rate (SSR) was higher in STnx rats, compared with the control group (P =.008), whereas S(P) was higher in the control group (P =.005). When CsA-treated groups were compared with non-CsA-treated ones, U(P) of the Unx rats not receiving CsA were significantly higher than the Unx rats receiving CsA (P =.026). Also, U(P) was higher in non-CsA-treated groups (P =.014), whereas S(CR) (P =.001), S(P) (P =.001), and PRS (P =.001) were higher in CsA-treated rats. In conclusion, we suggest that preserved renal mass is not enough to prevent CsA toxicity and that CsA should be administered to patients with both kidneys (eg, heart, pancreas recipients) as carefully as to patients with one functioning kidney (renal transplant recipients).

Animals↗

PubMed2006

Cost-effectiveness of hospital vaccination programs in North Carolina.

Although influenza and pneumonia are largely vaccine-preventable, vaccination coverage rates are well below Healthy People 2010 goals. The aim of this study was to examine the costs and cost-effectiveness of three provider-based vaccination interventions in the hospital setting: standing orders programs (SOPs), physician reminders (PRs), and pre-printed orders (PPOs). Data on program operating costs and the numbers of patients who received influenza or pneumococcal vaccinations were collected from nine North Carolina hospitals. Results demonstrated that the additional cost per patient vaccinated in 2004 was US dollars 58 for SOPs, US dollars 90 for PRs, and US dollars 412 for PPOs. These findings suggest that SOPs are a cost-effective approach for increasing adult vaccination coverage rates in hospital settings.

Adult↗

PubMed2006

The role of insulin-like growth factor-I and growth factor-associated signal transduction pathways in estradiol and progesterone facilitation of female reproductive behaviors.

We are examining the role of insulin-like growth factor-I (IGF-I) and downstream signal transduction pathways associated with growth factors (e.g., mitogen-activated protein kinase, MAPK) in estradiol and progesterone facilitation of female reproductive behavior in rats. Brain IGF-I receptor activity is required for the long-term, priming actions of estradiol on the female reproductive axis. Infusions of an IGF-I receptor antagonist during estradiol priming blocks induction of hypothalamic alpha(1B)-adrenergic receptors and luteinizing hormone surges, and attenuates lordosis behavior. Infusion of MAPK and phosphatidylinositol-3-kinase inhibitors inhibitors during estradiol priming completely blocks hormone-facilitated lordosis. Because progestin receptors (PRs) can be phosphorylated and activated by MAPKs, growth factor signaling pathways may also participate in progesterone facilitation of reproductive behaviors. Infusion of a MAPK inhibitor in estradiol-primed rats blocks progestin facilitation and sequential inhibition of lordosis and proceptive behaviors. Interference with MAPK signaling also inhibits behavioral responses to cGMP and a delta-opioid agonist, both of which can activate MAPK in some cells. Thus MAPK is involved in the facilitation of lordosis and proceptive behaviors, perhaps by phosphorylation of hypothalamic PRs.

Animals↗

PubMed2000

Clonality as expression of distinctive cell kinetics patterns in nodular hyperplasias and adenomas of the adrenal cortex.

Although histopathologic criteria for adrenal cortical nodular hyperplasias (ACNHs) and adenomas (ACAs) have been developed, their kinetics and clonality are virtually unknown. We studied 20 ACNHs and 25 ACAs (based on World Health Organization criteria) from 45 females. Representative samples were histologically evaluated, and the methylation pattern of the androgen receptor alleles was analyzed on microdissected samples. Consecutive sections were selected for slide cytometry, flow cytometry, and in situ end labeling (ISEL). Apoptosis was studied by flow cytometry (nuclear area/DNA content plotter analysis) and by ISEL. Appropriate tissue controls were run in every case. Polyclonal gel patterns were revealed in 14/18 informative ACNHs and in 3/22 informative ACAs, whereas monoclonal gel patterns were observed in 4/18 ACNHs and 19/22 ACAs. Overlapping proliferation rates (PRs) were observed in both clonal groups, and apoptosis was detected only in G(0)/G(1) cells, especially in monoclonal ACNHs (3/4; 75%) and in polyclonal ACAs (2/3; 67%). Significantly higher PRs were observed in ACNHs with polyclonal patterns and G(0)/G(1) apoptosis and in ACAs regardless of clonality pattern and presence of G(0)/G(1) apoptosis. All except one ACNH (19/20; 95%) and 15/25 ACAs (60%) showed diploid DNA content, whereas the remaining cases were hyperdiploid. A direct correlation between PR and ISEL was observed in polyclonal lesions (PR = 29.32 ISEL - 1.93), whereas the correlation was inverse for monoclonal lesions (PR = -9.13 ISEL + 21.57). We concluded that only simultaneous down-regulated apoptosis and high proliferation result in selective kinetic advantage, dominant clone expansion, and unbalanced methylation patterns of androgen receptor alleles in ACNHs and ACAs.

Adenoma↗

PubMed2003

The audible pop is not necessary for successful spinal high-velocity thrust manipulation in individuals with low back pain.

OBJECTIVE: To determine the relationship between an audible pop and symptomatic improvement with spinal manipulation in patients with low back pain (LBP). DESIGN: A prospective cohort study. SETTING: Two outpatient physical therapy clinics located in military medical centers. PARTICIPANTS: A cohort of 71 patients with nonradicular LBP referred to physical therapy. INTERVENTIONS: Participants underwent a standardized examination and standardized spinal manipulation treatment program. All patients were treated with a sacroiliac (SI) region manipulative technique and the presence or absence of an audible pop was noted. MAIN OUTCOME MEASURES: Subjects were reassessed 48 hours after the manipulation for changes in range of motion (ROM), numeric pain rating scale (PRS) scores, and modified Oswestry Disability Questionnaire (ODQ) scores. RESULTS: An audible pop occurred in 50 of the 71 subjects during the manipulative procedure. Both groups-those who had an audible pop and those who did not-improved over time in flexion ROM, PRS scores, and modified ODQ scores; however, there were no differences between groups (P>.05). Nineteen of the 71 (27%) patients improved dramatically (mean drop in modified ODQ, 67.6%). In 14 of the 19 dramatic responders, an audible pop occurred. However, the odds ratio (1.2; 95% confidence interval, 0.38-4.04) suggested that the occurrence of a manipulative pop would not improve the odds of achieving a dramatic reduction in symptoms after the manipulation. CONCLUSION: There is no relationship between an audible pop during SI region manipulation and improvement in ROM, pain, or disability in individuals with nonradicular LBP. Additionally, the occurrence of a pop did not improve the odds of a dramatic improvement with manipulation treatment.

Adolescent↗

PubMed2002

A novel progestogen receptor subtype in the Japanese eel, Anguilla japonica.

A cDNA encoding a second type of a progestogen receptor (ePR2) was isolated from the same library as we had previously cloned a functional PR (ePR1) in eel testis. The amino acid sequence of the ePR2 shows low homology with ePR1 (34%), but both PRs showed progestogen-dependent transactivation in transfection experiment. Tissue distribution of ePR2 mRNA was clearly different from that of ePR1. Protein interaction between two PRs was demonstrated in vitro by a glutathione S-transferase pull-down assay. These results indicate that ePR2 is also a functional PR. This is the first isolation of two different functional PR molecules from a vertebrate.

Animals↗

PubMed2000

A prospective, randomized controlled trial comparing the efficacy of recombinant follicle-stimulating hormone in three different in vitro fertilization protocols.

OBJECTIVE: To compare the following IVF protocols: a short protocol and long protocols starting on day 2 or day 21. All protocols used recombinant FSH (rFSH) for ovarian stimulation. DESIGN: Prospective, randomized study. SETTING: An assisted reproduction unit at a university center. PATIENT(S): Patients undergoing IVF (n = 150) were treated according to one of the three treatment protocols allocated by a random method. INTERVENTION(S): All patients used buserelin acetate and rFSH. Patients began the long protocol on day 2 (group 1) or day 21 (group 2) of the cycle. Patients in group 3 began the short protocol on day 2 of the cycle. MAIN OUTCOME MEASURE(S): Ovarian response, implantation rates, and pregnancy rates (PRs). RESULT(S): Patients treated with the short protocol (group 3) were stimulated in a shorter time, required less rFSH, and achieved higher E(2) levels. The numbers of follicles, oocytes, and embryos were similar in all three groups. The implantation rates were similar in groups 1 and 2 (11.8% and 13.3%, respectively), and both were higher than in group 3 (4.1%). Clinical PRs per oocytes retrieved were 19.6%, 18.6%, and 8.3% in groups 1, 2, and 3, respectively. CONCLUSION(S): The implantation rate was significantly higher with the long protocols than with the short protocol, with a tendency for a higher PR as well.

Adult↗

PubMed2002

Effect of diagnosis, age, sperm quality, and number of preovulatory follicles on the outcome of multiple cycles of clomiphene citrate-intrauterine insemination.

OBJECTIVE: To determine how diagnosis, age, sperm quality, and number of preovulatory follicles affect pregnancy rates when multiple cycles of clomiphene citrate (CC)-IUI are performed. DESIGN: Fifteen-year prospective observational study. SETTING: Private infertility clinic. PATIENT(S): Three thousand, three hundred eighty-one cycles of husband or donor IUI. INTERVENTION(S): Ovulation induction with CC and IUI. MAIN OUTCOME MEASURE(S): Per-cycle pregnancy rate (PR), cumulative pregnancy rate (CPR). RESULT(S): Pregnancy rates remained constant through four cycles, then fell significantly for diagnoses other than ovulatory dysfunction. Mean PRs for cycles 1-4 were significantly lower for patients with the following characteristics: age >/=43 years, poor semen quality, single preovulatory follicles, and diagnoses other than ovulatory dysfunction. Additional cycles of CC-IUI compensated for low PRs because of age, semen quality, or number of follicles. After four cycles, CPRs were 46% for ovulatory dysfunction; 38% for cervical factor, male factor, and unexplained infertility; 34% for endometriosis; and 26% for tubal factor. After six cycles, CPRs were 65% for ovulation dysfunction, 35% for endometriosis, and unchanged for other diagnoses. CONCLUSION(S): Clomiphene citrate-intrauterine insemination should be performed for a minimum of four cycles. Additional cycles of CC-IUI can compensate for low pregnancy rates due to age, semen quality, or follicle number in patients with ovulation dysfunction.

Aging↗

PubMed1985

Relation between steroid receptor levels and prolactin level in the decidua of early human pregnancy.

To clarify the relation between steroids and prolactin (PRL) production in human decidua, the levels of estrogen receptors (ERs), progesterone receptors (PRs), and androgen receptors (ARs) and the level of PRL in the decidua were determined simultaneously during early pregnancy. Cytosol, nuclear, and total ER levels and the cytosol PRL level were found to increase with the advance of gestation; whereas levels of PRs and ARs remained constant. Multiple regression analysis showed that the multiple correlation coefficient in the relationships of cellular ERs and cytosol PRL with gestational age was 0.722 and relatively high among the others. These results suggest an association between estrogen and decidual growth. Significant correlations between the cytosol PRL level and cellular PR or AR levels were seen during early pregnancy, suggesting that progestin and androgen may regulate PRL synthesis.

Cytosol↗