Low dose clomiphene citrate as a mild stimulation protocol in women with unsuspected poor in vitro fertilization result can generate more oocytes with optimal cumulative pregnancy rate.

BACKGROUND: The use of long protocol during controlled ovarian stimulation for assisted reproduction attracts high dosage of gonadotropins. High dose of gonadotropins can be detrimental to oocyte development, which affects its quality and compromises the treatment outcome. Mild stimulation protocols that attract low dose gonadotropins could be useful alternative regimen to address such problems. This study evaluated the efficacy of low dose clomiphene citrate based protocol plus low dose gonadotropins on predicted normal responder patients who had unsuspected poor in vitro fertilization (IVF) result, following an initial stimulation with long gonadotropin-releasing hormone (GnRH) agonist protocol. METHODS: This a retrospective study of 65 infertile women who underwent 130 cycles in our center from January 2011 to December 2014. The initial IVF cycle (Group 1) was treated with long GnRH-a protocol plus a high dose of gonadotropins (≥150 IU/d), while second IVF cycle (Group 2) had low dose clomiphene citrate based protocol plus low dose gonadotropins (75-112.5 IU/d). RESULTS: The rate of cumulative pregnancy/started cycle (9.2% [6/65] vs. 51% [33/65]; P < 0001) was significantly better in CC protocol than the long GnRH agonist protocol. The number of oocytes retrieved was also higher in CC protocol compared to the long protocol (7.26 ± 1.95 vs. 5.98 ± 1.31; P = 0.03). There was a lower number of patients without embryos (12.31% vs. 33.85%; p < 0.0001) in CC protocol than long protocol. CONCLUSIONS: This study showed a better cumulative pregnancy rate in the low dose CC based protocol. There was a higher number of oocytes retrieved after using a lower total dose of recombinant FSH in CC protocol. Thus, clomiphene treatment plus low dose rFSH can be an alternative option for such patients in second cycle stimulation instead of repeating long protocol regimen. Randomized controlled studies with larger number of patients will be needed for more accurate evidence.

Therapeutic effect of acupuncture on the outcomes of in vitro fertilization: a systematic review and meta-analysis.

PURPOSE: Controversial results have been reported concerning the effect of acupuncture on in vitro fertilization (IVF) outcomes. The current review was conducted to systematically review published studies of the effects of acupuncture on IVF outcomes. METHODS: Women undergoing IVF in randomized controlled trials (RCTs) were evaluated for the effects of acupuncture on IVF outcomes. The treatment groups involved traditional, electrical, laser, auricular, and other acupuncture techniques. The control groups consisted of no, sham, and placebo acupuncture. The PubMed, Embase, and Web of Science databases were searched. The pregnancy outcomes data are expressed as odds ratios (ORs) with 95% confidence intervals (CIs) based on a fixed model or random model depending on the heterogeneity determined by the Q test and I2 statistic. The major outcomes were biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), live birth rate (LBR), and ongoing pregnancy rate (OPR). Heterogeneity of the therapeutic effect was evaluated by a forest plot analysis, and publication bias was assessed by a funnel plot analysis. RESULTS: Thirty trials (a total of 6344 participants) were included in this review. CPR data showed a significant difference between the acupuncture and control groups (OR 1.26, 95% CI 1.06-1.50, p = 0.01), but there was significant statistical heterogeneity among the studies (p = 0.0002). When the studies were restricted to Asian or non-Asian area trials with a sensitivity analysis, the results significantly benefited the CPR in Asian group (OR 1.51, 95% CI 1.04-2.20, p = 0.03). Based on the area subgroup analysis, we found that in the Asian group, the IVF outcomes from the EA groups were all significantly higher than those from the control groups (CPR: OR 1.81, 95% CI 1.20-2.72, p = 0.005; BPR: OR 1.84, 95% CI 1.12-3.02, p = 0.02; LBR: OR 2.36, 95% CI 1.44-3.88, p = 0.0007; OPR: OR 1.94, 95% CI 1.03-3.64, p = 0.04). Meanwhile, compared with other acupuncture time, the IVF outcome results were significantly superior in the acupuncture group when acupuncture was conducted during controlled ovarian hyperstimulation (COH) (CPR: OR 1.71, 95% CI 1.27-2.29, p = 0.0004; LBR: OR 2.41, 95% CI 1.54-3.78, p = 0.0001; BPR: OR 1.50, 95% CI 1.02-2.20, p = 0.04; OPR: OR 1.88, 95% CI 1.06-3.34, p = 0.03). However, when acupuncture was conducted at the time of embryo transfer, the BPR and OPR from the acupuncture groups were significantly lower than those of the controls in the Asian group (BPR: OR 0.67, 95% CI 0.48-0.92, p = 0.01; OPR: OR 0.68, 95% CI 0.49-0.96, p = 0.03). CONCLUSIONS: Based on an analysis of the studies, acupuncture improves the CPR among women undergoing IVF. When the studies were restricted to Asian or non-Asian area patients, compared with traditional acupuncture and other methods, electrical acupuncture yielded better IVF outcomes. Optimal positive effects could be expected using acupuncture in IVF during COH, especially in Asian area. However, as a limitation of this review, most of the included studies did not mention the number of embryos transferred.

Chromosomal copy number analysis on chorionic villus samples from early spontaneous miscarriages by high throughput genetic technology.

BACKGROUND: About 10 -15 % of all clinically recognized pregnancies result in spontaneous miscarriages, and chromosomal abnormalities are the most common reason. The conventional karyotyping on chorionic villus samples (CVSs) is limited by cell culture and its resolution. This study aimed at evaluating the efficiency of the application of high throughput genetic technology, including array comparative genomic hybridization (array CGH) and next generation sequencing (NGS) on the chromosomal copy number analysis of CVSs from early spontaneous miscarriages. RESULTS: Four hundred and thirty-six CVSs from early spontaneous abortion were collected. Genomic DNA was extracted using a routine method, and the chromosomal copy number variants (CNVs) were analyzed by array CGH and NGS. Two hundred and twenty-five samples (51.6 %) with abnormal chromosomes were identified among 436 samples, of which 188 samples (41.3 %) were aneuploidy, 23 samples (5.3 %) were segmental deletion and/or duplication cases, and 14 samples (3.2 %) were triploid. Two of the three cases with small segmental deletion and duplication were validated to be transferred from their fathers who were carriers of submicroscopic reciprocal translocation. CONCLUSION: A high chromosomal abnormality detection rate on CVSs from early spontaneous miscarriage was achieved by array CGH and NGS. Specifically, the detection of submicroscopic recombination, which is sometimes missed by conventional karyotyping, was important for genetic counseling for the couples that suffered from recurrent miscarriages.