[Effects, safety and cost-benefit analysis of Down syndrome screening in first trimester].

OBJECTIVE: To investigate the effects, safety and cost-benefit analysis of Down syndrome screening in first trimester. METHODS: From January 2009 to December 2012, 43 729 pregnant women undergoing 3 methods of Down syndrome traditional screening strategies in Shenzhen Maternity and Child Healthcare Hospital were studied retrospectively, including in 17 502 cases in pregnancy associated plasma protein A (PAPP-A) and free ß-hCG measured biochemistry screening, 14 080 cases in nuchal translucency (NT) screening and 12 147 cases in combined screening, meanwhile, 7 389 cases on non-invasive fetal trisomy test (NIFTY) were performed in Huada Gene Research Institute(BGI). The effects and safety of four screening strategies were assessed throughout a decision tree. The economical characters of each screening strategy were compared by cost-effectiveness analysis as well as cost-benefit analysis. RESULTS: (1) The effects of four strategies are: NIFTY > combined screening > NT screening > biochemistry screening. (2) The safety of four strategies are: NIFTY > combined screening > NT screening > biochemistry screening. (3) Cost-effectiveness analysis and cost-benefit analysis:the biochemistry screening has lowest cost-effectiveness ratio (CER) and highest cost-benefit ratio (CBR), which performed a better economical efficiency. The incremental CER of three traditional screening strategies are all less than the economical burden of Down syndrome.NIFTY has highest CER and negative net present value (NPV), NPV would be positive and CBR would be more than 1 if the price of NIFTY reduce to 1 434 Yuan. CONCLUSIONS: Combined screening possess best screening efficiency, while biochemistry screening was demonstrated more economical in traditional screening.NIFTY is the future of Down syndrome screening.

Spontaneous coronary artery dissection associated with ß-HCG injections and fibromuscular dysplasia.

Spontaneous coronary artery dissection (SCAD) is an infrequent cause of acute coronary syndrome predominantly affecting younger women. SCAD is often associated with predisposing arterial abnormalities and precipitating emotional, physical, and hormonal stressors. We previously showed that fibromuscular dysplasia is strongly associated with SCAD and may be a causative factor. Hormonal changes related to pregnancy and sex hormones have also been shown to be an important cause of SCAD. We describe the first case report, to our knowledge, of SCAD associated with ß-human growth hormone injections in a patient with concomitant FMD.

Triggering final oocyte maturation with reduced doses of hCG in IVF/ICSI: a prospective, randomized and controlled study.

OBJECTIVE: To compare the effectiveness of urinary human chorionic gonadotropin (u-hCG) at reduced doses of 4000 IU and 6000 IU in inducing final oocyte maturation during in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles. STUDY DESIGN: 164 patients with an indication for IVF or ICSI recruited in this randomized, single-blinded and controlled study in IVF clinic at the Sun Yat-sen Memorial Hospital. Patients were prospectively randomized to receive 4000 IU (Group A, n=83) and 6000 IU (Group B, n=81) of hCG for triggering final oocyte maturation. Number or percentage of mature oocytes retrieved per patient, fertilization rates, pregnancy rates were the main outcome measures. RESULTS: No evidence of statistically significant difference in the number or proportion of mature oocytes retrieved was observed in both groups. The lower fertilization rate and significantly lower clinical pregnancy rate were observed in Group A. The ovarian hyperstimulation syndrome (OHSS) rates in both groups were also similar. In the subgroup of BMI< 20 kg/m(2), fertilization rate were significantly higher in the administration group of hCG at the dose of 6000 IU when compared with the dose of 4000 IU (82.40% vs. 70.92%, P=0.017); in contrast, no significant difference in clinical pregnancy rates was observed in both groups. In the subgroup of BMI 20-25 kg/m(2), clinical pregnancy rates were significantly higher in patients treated with hCG at dose of 6000 IU than patients treated with hCG at dose of 4000 IU (65.3% vs. 35.0%, P=0.004); however, no significant difference in fertilization rates was observed. CONCLUSION: Both doses of u-hCG revealed an equal effect on the induction of final oocyte maturation in the patients with moderate or high ovarian response; however, the reduced dose of hCG could result in an obvious impact on clinical pregnancy rates and did not exhibit an obvious effect on OHSS rates.

The beta-hCG+erythropoietin in acute stroke (BETAS) study: a 3-center, single-dose, open-label, noncontrolled, phase IIa safety trial.

BACKGROUND AND PURPOSE: Animal data suggest the use of beta-human chorionic gonadotropin followed by erythropoietin to promote brain repair after stroke. The current study directly translated these results by evaluating safety of this sequential growth factor therapy through a 3-center, single-dose, open-label, noncontrolled, Phase IIa trial. METHODS: Patients with ischemic stroke 24 to 48 hours old and National Institutes of Health Stroke Scale score of 6 to 24 started a 9-day course of beta-human chorionic gonadotropin (once daily on Days 1, 3, and 5 of study participation) followed by erythropoietin (once daily on Days 7, 8, and 9 of study participation). This study also evaluated performance of serially measured domain-specific end points. RESULTS: A total of 15 patients were enrolled. Two deaths occurred, neither related to study medications. No safety concerns were noted among clinical or laboratory measures, including screening for deep vein thrombosis and serial measures of serum hemoglobin. In several instances, domain-specific end points provided greater insight into impairments as compared with global outcome measures. CONCLUSIONS: Results support the safety of this sequential, 2-growth factor therapy initiated 24 to 48 hours after stroke onset.

Desarrollo de síndrome de hiperestimulación ovárica grave tras la administración exógena de gonadotropina coriónica humana / Severe ovarian hyperstimulation syndrome after exogenous administration of human chorionic gonadotropin

El síndrome de hiperestimulación ovárica grave esuna entidad clínica que puede ocurrir tras la administraciónde gonadotropina coriónica humana, utilizadapara inducir la ovulación en las pautas de estimulaciónovárica de la fecundación in vitro. Presentamos el casode una mujer de 27 años, que tras recibir tratamientocon gonadotropina y ser sometida a fertilización in vitroconsiguiendo gestación, presentó un cuadro clínico dedolor abdominal, ascitis, edemas en miembros inferiores,disnea, derrame pleural bilateral y síndrome de distrésrespiratorio del adulto. La paciente precisó ingreso en launidad de cuidados intensivos y ventilación mecánica,así como la realización de legrado uterino para frenar laprogresión del cuadro(AU)

Severe ovarian hyperstimulation syndrome can occurafter administration of human chorionic gonadotropinused to induce ovulation in the context of in-vitrofertilization protocols. We report the case of a 27-yearoldwoman who had received gonadotropin treatment.In-vitro fertilization was successful but she developedabdominal pain, ascites, lower limb edema, dyspnea,bilateral pleural effusion, and adult respiratory distresssyndrome. The patient was admitted to the intensive careunit, where mechanical ventilation was started. Uterinedilatation and curettage was required to halt the process(AU)

Immunologic hazards associated with vaccination of humans.

Universal vaccination remains the most effective measure for preventing the spread of many infectious diseases. Since vaccination is one of the few medical interventions applied to healthy individuals, its safety must be as absolute as human efforts can make it. Questions have been raised recently about the possibility that particular vaccines can trigger or promote autoimmune disease, although controlled, population-based studies have not supported this notion. In collaboration with the World Health Organization, we investigated a subunit vaccine of human chorionic gonadotropin, and found evidence of benign, but not pathologic, autoimmunity. We propose an algorithm for systematic study of possible immunologic hazards of vaccines in animals and human subjects.

The HSD-hCG vaccine prevents pregnancy in women: feasibility study of a reversible safe contraceptive vaccine.

PROBLEM: To develop a vaccine for reversible control of fertility in women. MATERIALS AND PROTOCOLS: Purified beta subunit of hCG annealed to purified alpha subunit of ovine LH linked chemically to tetanus toxoid (TT) and diphtheria (DT); vaccine employed at 300 micrograms gonadotropin equivalent per injection adsorbed on alhydrogel with 1 mg SPLPS added in the first injection; Phase I safety trials in 47 women with elective tubal ligation; Phase II efficacy studies in 148 proven fertile women (2 children), sexually active, desirous of family planning using IUD; IUD removed when anti-hCG titres exceed 50 ng/ml hCG bioneutralization capacity; boosters given to maintain above threshold antibody levels; post coital tests conducted in 8 volunteers; sera of protected women analysed for immuno-determinants recognized by competitive enzyme immunoassays employing a panel of monoclonal antibodies and by direct binding to synthetic peptides; recombinant vaccines expressing beta hCG as a secreted product or as a fused protein anchored on membrane. RESULTS: Immunization was well tolerated with no significant changes in endocrine, metabolic and hematological indices. Normal ovulatory cycles were maintained as indicated by menstrual regulation. The vaccine was highly effective in preventing pregnancy (1 pregnancy in 1224 cycles ) at and above antibody titres of 50 ng/ml. Antibodies declined in course of time in absence of boosters, with conceptions occurring below 35 ng/ml titres indicating regain of fertility. Ability of antibodies to prevent pregnancy was confirmed by post coital tests. High avidity (10(10) M-1) and other characteristics of antibodies generated by the vaccine are described and compared with those induced by two other hCG vaccines having undergone Phase I trials. The antibody response of the HSD vaccine in humans is characterized predominantly to an epitope recognized by the monoclonals 206 and P3W80. The antibodies had low or no reactivity with the carboxy terminal peptide and 38-57 region peptide. Live recombinant vaccines expressing beta hCG as a membrane anchored peptide generated antibody response to hCG in all animals following a single injection. CONCLUSIONS: Reversible fertility control is feasible with the HSD-hCG vaccine without impairment of ovulation or disturbance of menstrual regularity. Suggestions have been made for further optimization of the vaccine, which include replacement of TT and DT by a panel of T non B determinants communicating with the entire MHC spectrum and development of recombinant vaccine expressing beta hCG along with membrane anchored carrier.

Effects of a beta-human chorionic gonadotropin subunit immunogen administered in aqueous solution with a novel nonionic block copolymer adjuvant in patients with advanced cancer.

The clinical and immunological effects of a vaccine consisting of CTP37, a synthetic peptide corresponding to the COOH-terminal peptide (CTP) of beta-human chorionic gonadotropin (beta-hCG) conjugated to diphtheria toxoid, combined with CRL 1005, a novel synthetic nonionic block copolymer adjuvant, were examined. Twenty-one patients with metastatic, nontrophoblastic cancers received up to four immunizations by i.m. injection of a fixed dose of CTP37 and escalating doses of CRL 1005. Doses of CRL 1005 adjuvant as high as 75 mg were administered with 1 mg of CTP37 without evidence of significant local or systemic toxicity. Immunizations resulted in the production of IgG antibody to beta-hCG. CRL 1005 doses of 3-25 mg appeared to be optimal for antibody induction. Immunizations also resulted in increases in the cellular response of peripheral blood mononuclear cells (PBMCs) to the unconjugated CTP, hCG, and diphtheria toxoid. Responding PBMCs specifically secreted the TH1-associated cytokines IFN-gamma and interleukin (IL)-2 as well as the TH2-associated IL-5 and IL-10. Increased expression of IFN gamma and IL-5 mRNAs by PBMCs 4 h after immunization was also observed. CRL 1005 administered with CTP37 in aqueous solution is well tolerated. The CTP37-CRL 1005 subunit vaccine has the capacity to stimulate potentially beneficial humoral and cellular immune responses in patients with advanced cancer.