Yulian Zhao

Impact of semen characteristics on the success of intrauterine insemination.

AbstractPatients: To evaluate the influence of sperm characteristics on the outcome of infertility treatment using intrauterine insemination (IUI). Methods: Retrospective study of 431 infertility couples who underwent 1007 IUI treatment cycles from June 1999 to October 2002. Sperm parameters before and after preparation for IUI were evaluated and correlated with pregnancy outcome. Results: Clinical pregnancy occurred in 12% of cycles and 28% of patients. Initial sperm motility and processed forward progression were independently associated with pregnancy after IUI. The mean number of cycles per patient was 4.3. Although pregnancy rate per cycle did not differ from cycle to cycle, the cumulative pregnancy rate approached plateau after five cycles. Conclusions: Sperm motility is an independent factor influencing IUI-related pregnancy. A forward progression score of 3 to 4 in a processed specimen is necessary for IUI success. The number of IUI attempts per patient should be individualized depending upon the needs of patients.

The Ethical, Legal, and Social Issues Impacted by Modern Assisted Reproductive Technologies

Background. While assisted reproductive technology (ART), including in vitro fertilization has given hope to millions of couples suffering from infertility, it has also introduced countless ethical, legal, and social challenges. The objective of this paper is to identify the aspects of ART that are most relevant to present-day society and discuss the multiple ethical, legal, and social challenges inherent to this technology. Scope of Review. This paper evaluates some of the most visible and challenging topics in the field of ART and outlines the ethical, legal, and social challenges they introduce. Major Conclusions. ART has resulted in a tectonic shift in the way physicians and the general population perceive infertility and ethics. In the coming years, advancing technology is likely to exacerbate ethical, legal, and social concerns associated with ART. ART is directly challenging society to reevaluate the way in which human life, social justice and equality, and claims to genetic offspring are viewed. Furthermore, these issues will force legal systems to modify existing laws to accommodate the unique challenges created by ART. Society has a responsibility to ensure that the advances achieved through ART are implemented in a socially responsible manner.

Clinical impact of scavenger receptor class B type I gene polymorphisms on human female fertility

BACKGROUND The goal of this study was to evaluate the association of SCARB1 single nucleotide polymorphisms (SNPs) and fertility outcomes in women undergoing IVF. METHODS Between November 2007 and March 2010, granulosa cells and follicular fluid were collected from women undergoing IVF. Five SCARB1 SNPs were sequenced and progesterone levels were measured in the follicular fluid. Fertility measurements were defined as the presence of gestational sac(s) and fetal heartbeat(s). RESULTS The study group consisted of 274 women (mean age of 36.4 ± 4.6 years). The racial/ethnic composition was 55% Caucasian (n = 152), 25% African-American (n = 68), 12% Asian (n = 34), 5% Hispanic, (n = 14) and 2% other (n = 6). There was a significant difference in the genotype frequencies of the SCARB1 SNPs across the groups. Subjects who were homozygous for the minor allele in the rs5888 SNP had higher follicular progesterone levels than those who were homozygous for the major allele (P = 0.03). In the Caucasian group, carriers of the minor A allele of the rs4238001 SNP had lower follicular progesterone levels compared with homozygous carriers of the major G allele (P = 0.04). In this group, follicular progesterone levels were highly predictive of the rs4238001 SNP (P = 0.03). In the entire cohort, minor allele carriers of rs4238001 did not have any viable fetuses at Day 42 following embryo transfers (P = 0.04). In the African-American group in particular, there was also an association between rs10846744 and gestational sac(s) (P = 0.006), and fetal heartbeat(s) (P = 0.005). CONCLUSIONS In part, SCARB1 rs4238001 and rs10846744 SNPs may contribute to human female infertility.

Blastocoel fluid from differentiated blastocysts harbors embryonic genomic material capable of a whole-genome deoxyribonucleic acid amplification and comprehensive chromosome microarray analysis

OBJECTIVE To obtain embryonic molecular karyotypes from genomic DNA (deoxyribonucleic acid) isolated from blastocoel fluid (BF) and to compare these karyotypes with the karyotypes from the remaining inner cell mass (ICM) and trophectoderm (TE) of the blastocyst. DESIGN Prospective cohort study. SETTING Academic center and preimplantation genetics laboratory. PATIENT(S) Ninety-six donated cryopreserved embryos. INTERVENTION(S) Embryo biopsy, BF aspiration, DNA analysis using a comparative genomic hybridization microarray (aCGH). MAIN OUTCOME MEASURE(S) The aCGH of a single blastomere, BF-DNA, and ICM-TE. RESULT(S) The BF-DNA samples resulted in a successful aCGH in 63% of cases. Discordance in karyotypes was found between the BF-DNA and the ICM-TE in 52% of cases. A total of 70% of aneusomic (mosaicism), cleavage-stage embryos differentiated into euploid blastocysts. Probabilities for diagnostic accuracy were calculated and demonstrated the following: sensitivity of 0.88 (95% confidence interval [CI]: 0.62-0.98); specificity of 0.55 (95% CI: 0.39-0.70); positive predictive value of 0.41 (95% CI: 0.25-0.60); negative predictive value of 0.92 (95% CI: 0.75-0.99). CONCLUSION(S) Genomic DNA from the BF can be amplified and characterized by comprehensive chromosome microarrays. The results demonstrated that aneusomic cleavage-stage embryos differentiated into euploid blastocysts, possibly using a mechanism that marginalizes aneuploid nuclei into the blastocoel cavity. In addition, owing to the high discordance between the karyotypes obtained from the BF-DNA and the ICM-TE, using BF-DNA for preimplantation genetic testing is not yet advised.

The impact of luteal phase support on gene expression of extracellular matrix protein and adhesion molecules in the human endometrium during the window of implantation following controlled ovarian stimulation with a GnRH antagonist protocol

OBJECTIVE To evaluate the impact of two different luteal phase support protocols on gene expression of extracellular matrix (ECM) proteins and adhesion molecules in the human endometrium. DESIGN Eighty-four ECM protein and adhesion molecule genes were analyzed using array-based reverse-transcription polymerase chain reaction. SETTING Academic hospital. PATIENT(S) Nine oocyte donors. INTERVENTION(S) Endometrial biopsies were obtained on the day of oocyte retrieval (group I) and 3-5 days later (group II) after randomization into 3 groups. Group IIa had no luteal phase support, group IIb had luteal support with micronized progesterone, and group IIc had luteal support with progesterone plus 17β-estradiol. MAIN OUTCOME MEASURE(S) Gene expression profiles in relation to different types of luteal phase support protocols. RESULT(S) Compared with the day of retrieval (group I), 24 genes were significantly up-regulated (4 in group IIa, 14 in group IIb, 22 in group IIc) and 14 genes were down-regulated (5 in group IIa, 2 in group IIb, 10 in group IIc) on day 3-5 (P<.05). In the luteal support group, up- regulation occurred predominantly in genes encoding for matrix metallopeptidases (MMP10, MMP3, MMP9), integrins (ITGA3, ITGA5, ITGB3, ITGB4), and laminin (LAMB3). In contrast, the most significant suppression was documented in genes encoding for catenin-D2, collagen-11A1, and the laminins (LAMA1 and LAMA3). Significant changes between groups IIb and IIc were also observed in 9 genes. CONCLUSION(S) Luteal phase support following controlled ovarian stimulation has a profound impact on the ECM pathway targeted genes.

Effect of luteal-phase support on endometrial microRNA expression following controlled ovarian stimulation

BackgroundStudies suggested that microRNAs influence cellular activities in the uterus including cell differentiation and embryo implantation. In assisted reproduction cycles, luteal phase support, given to improve endometrial characteristics and to facilitate the implantation process, has been a standard practice. The effect of different types of luteal phase support using steroid hormones in relation to endometrial miRNA profiles during the peri-implantation period has not seen described. This study was designed to evaluate the expression of miRNAs during the luteal phase following controlled ovarian stimulation for IVF and the influence of different luteal phase support protocols on miRNA profiles.MethodsThe study was approved by the Johns Hopkins Hospital Institutional Review Board. Endometrial biopsies were obtained on the day of oocyte retrieval from 9 oocyte donors (group I). An additional endometrial biopsy was obtained 3–5 days later (Group II) after the donors were randomized into three groups. Group IIa had no luteal-phase support, group IIb had luteal support with micronized progesterone (P), and Group IIc had luteal support with progesterone plus 17-beta-estradiol (P + E). Total RNA was isolated and microarray analysis was performed using an Illumina miRNA expression panel.ResultsA total of 526 miRNAs were identified. Out of those, 216 miRNAs were differentially regulated (p < 0.05) between the comparison groups. As compared to the day of retrieval, 19, 11 and 6 miRNAs were differentially regulated more than 2 fold in the groups of no support, in the P support only, and in the P + E support respectively, 3–5 days after retrieval. During the peri-implantation period (3–5 days after retrieval) the expression of 33 and 6 miRNAs increased, while the expression of 3 and 0 miRNAs decreased, in the P alone and in the P + E group respectively as compared to the no steroid supplementation group.ConclusionLuteal support following COS has a profound influence on miRNA profiles. Up or down regulation of miRNAs after P or P + E support suggest a role(s) of luteal support in the peri-implantation uterus in IVF cycles through the regulation of associated target genes.

Nitric oxide metabolite production in the human preimplantation embryo and successful blastocyst formation

Eleven patients underwent controlled ovarian hyperstimulation yielding 72 embryos for evaluation. Mean nitric oxide metabolite levels in the insemination media were 2.6 times higher in embryos that progressed to blastocysts by culture day 5 than in those that did not. A comparison of the receiver operating characteristic curves between morphological predictors and nitric oxide metabolite levels revealed a trend toward a stronger association of insemination media nitric oxide metabolite with blastocyst formation.

SUCCESSFUL MANAGEMENT OF INFERTILITY DUE TO RETROGRADE EJACULATION USING ASSISTED REPRODUCTIVE TECHNOLOGIES: A REPORT OF TWO CASES

Although retrograde ejaculation is a relatively uncommon cause of infertility, it is nonetheless the most common cause of ejaculatory dysfunction. Retrograde ejaculation is characterized by either all or part of the seminal fluid going into the bladder. The initial management of patients with ejaculatory dysfunction is medical therapy. In couples who have failed medical therapy, assisted reproductive techniques using sperm harvested from either the urine or the male reproductive tract would be the ultimate option. We report successful management of two couples, both men with advanced age and complete retrograde ejaculation, by intrauterine insemination in one and in vitro fertilization (IVF) using intracytoplasmic sperm injection (ICSI) in the other using sperm harvested from urine. The cases reported herein suggest that male infertility due to retrograde ejaculation may be successfully treated in men significantly older than the usual reproductive age and that traditional methods of hydration and urine alkalinization allow for the successful recovery of fertile sperm for ART. The selection of the method of ART must be individualized to the needs of each couple based upon both male and female factors.

Assisted reproduction: Ethical and legal issues

Since inception, the use of assisted reproductive technologies (ART) has been accompanied by ethical, legal, and societal controversies. Guidelines have been developed to address many of these concerns; however, the rapid evolution of ART requires their frequent re-evaluation. We review the literature on ethical and legal aspects of ART, highlighting some of the most visible and challenging topics. Of specific interest are: reporting of ART procedures and outcomes; accessibility to ART procedures; issues related to fertility preservation, preimplantation genetic testing, gamete and embryo donation, and reproductive outcomes after embryo transfer. Improvements in ART reporting are needed nationally and worldwide. Reporting should include outcomes that enable patients to make informed decisions. Improving access to ART and optimizing long-term reproductive outcomes, while taking into account the legal and ethical consequences, are challenges that need to be addressed by the entire community of individuals involved in ART with the assistance of bioethicists, legal counselors, and members of society in general.

The impact of luteal phase support on endometrial estrogen and progesterone receptor expression: a randomized control trial

BackgroundTo assess the impact of luteal phase support on the expression of estrogen receptor (ER) alpha and progesterone receptors B (PR-B) on the endometrium of oocyte donors undergoing controlled ovarian hyperstimulation (COH).MethodsA prospective, randomized study was conducted in women undergoing controlled ovarian hyperstimulation for oocyte donation. Participants were randomized to receive no luteal support, vaginal progesterone alone, or vaginal progesterone plus orally administered 17 Beta estradiol. Endometrial biopsies were obtained at 4 time points in the luteal phase and evaluated by tissue microarray for expression of ER alpha and PR-B.ResultsOne-hundred and eight endometrial tissue samples were obtained from 12 patients. No differences were found in expression of ER alpha and PR-B among all the specimens with the exception of one sample value.ConclusionsThe administration of progesterone during the luteal phase of COH for oocyte donor cycles, either with or without estrogen, does not significantly affect the endometrial expression of ER alpha and PR.