Using family members as gamete donors or gestational carriers The use of adult intrafamilial gamete donors and gestational surrogates is generally ethically acceptable when all participants are fully informed and counseled, but consanguineous arrangements or ones that simulate incestuous unions should be prohibited. Adult child-to-parent arrangements require caution in order to avoid coercion, and parent-to-adult child arrangements are acceptable in limited situations. Programs that choose to participate in intrafamilial arrangements should be prepared to spend additional time counseling participants and ensuring that they have made free, informed decisions.
The most well kept secret, embryo culture media: a smart reveal from an expert The introduction of in vitro fertilization (IVF) treatments was only possible when all those investigations that took place in tissue culture were adapted for human embryos. But human embryo culture is very different from other cell culture, because somatic cells are surrounded by the extracellular fluid rich in nutrients whereas embryos are simply bounded by a very low amount of uterine fluid that reflects location and chronologic changes (1). Since the beginning of assisted reproductive technology (ART) in the 1980s, media conception, configuration, and composition may have changed dramatically, and we may consider that a portion of the improved success in IVF programs came along with enhanced formulations and detailed user protocols (2).
Healthy diets and men's contribution to fertility; is semen quality good enough? In this issue of Fertility and Sterility, Oostingh and colleagues (1) report an association between greater adherence to a data-derived “healthy” dietary pattern, characterized by higher intakes of legumes, vegetables, cereals, fruits, and olive oil, and higher semen quality—particularly sperm concentration and progressive motility—among men from couples planning pregnancy. This article adds to the growing literature relating adherence to healthy diet patterns and greater semen quality including previous work from this group among couples undergoing infertility treatment, as well as work from other groups including studies reporting higher semen quality with greater adherence to healthy diets among men in the United States, Europe and Asia (2, 3).
Long-awaited long-term follow-up of reproductive parameters in female offspring conceived with the use of intracytoplasmic sperm injection There have been great advances in many assisted reproduction laboratory techniques and procedures since the first successful live birth as a result of in vitro fertilization (IVF) in 1978. One of the most notable overall, particularly for the treatment of male-factor infertility, was the advent of intracytoplasmic sperm injection (ICSI). Although many clinicians and patients who have benefitted from this technology hail it as a breakthrough, there are questions regarding how the need to use this technique to achieve reproductive success may affect future generations; one particular area of interest in this regard is the potential for reproductive success in the offspring.
ASRM standard embryo transfer protocol template: a committee opinion Standardization improves performance and safety. A template for standardizing the embryo transfer procedure is presented here with 12 basic steps supported by published scientific literature and a survey of common practice of SART programs; it can be used by ART practices to model their own standard protocol.
Guidance on the limits to the number of embryos to transfer: a committee opinion Based on American Society for Reproductive Medicine (ASRM) and Society for Assisted Reproductive Technology data available through 2014, ASRM's guidelines for the limits on the number of embryos to be transferred in in vitro fertilization (IVF) cycles have been further refined in continuing efforts to promote singleton gestation and reduce the number of multiple pregnancies. This version replaces the document titled Criteria for number of embryos to transfer: a committee opinion that was published most recently in August of 2013 (Fertil Steril 2013;99:44–6).
Obesity pandemic: causes, consequences, and solutions—but do we have the will? Obesity has become pandemic owing to an obesogenic environment (inexpensive calorie dense food, technologies and structure of communities that reduce or replace physical activity, and inexpensive nonphysical entertainment) and excessive emphasis on low fat intake resulting in excessive intake of simple carbohydrates and sugar. Effects are greater for women owing to their smaller size and extra weight gain with each pregnancy, with 38% of American adult women being obese. Women are responsible for more than three-fourths of the more than 400 billion dollars of excess direct health care expenditures due to obesity.
Obesity and female infertility: potential mediators of obesity's impact The worldwide upward trend in obesity has been dramatic, now affecting more than 20% of American women of reproductive age. Obesity is associated with many adverse maternal and fetal effects prenatally, but it also exerts a negative influence on female fertility. Obese women are more likely to have ovulatory dysfunction due to dysregulation of the hypothalamic-pituitary-ovarian axis. Women with polycystic ovarian syndrome who are also obese demonstrate a more severe metabolic and reproductive phenotype.
Vasectomy reversal semen analysis: new reference ranges predict pregnancy To study the semen analysis values required to cause a pregnancy after vasectomy reversal (VR). Vasectomy reversal is increasingly performed on men who wish to regain fertility after elective sterilization. Despite a thorough understanding of predictors of vasal patency after surgery, little is known about the patients’ semen parameters and pregnancy potential.
Microsurgical excision of testicular mass The video article by Sávio et al. (1). nicely demonstrates a potentially testis-preserving procedure used for either impalpable testicular tumors picked up on ultrasound or palpable tumors in men with a solitary functioning testis. I described a technique for ultrasound-guided needle localization and microsurgical excision of nonpalpable testicular tumors in 2002 (2). This video is a good demonstration of the technique.
A 2-dose GnRH Agonist trigger maintains supraphysiologic LH levels until the time of oocyte retrieval The use of GnRH agonist (GnRHa) to induce final oocyte maturation in IVF has become increasingly common due to its proven ability to reduce the incidence of OHSS. It has previously been demonstrated that the LH surge induced by a single bolus of GnRHa at mid-cycle results in a shorter LH surge than in natural cycles, with LH levels returning to baseline levels after ∼24 hours (Olivennes, 1996). There has been concern, therefore, that the GnRHa-induced LH surge may not adequately induce maturation and full developmental competence of the oocytes.
ART outcomes with the afterload transfer technique The embryo transfer procedure is crucial to the outcome of assisted reproduction (ART) treatment cycles. It is a loosely standardized procedure with variables which have been shown to affect implantation rates and patient outcomes. Despite the importance of the embryo transfer, there is limited data investigating its many technical aspects. We sought to study the effect of the afterload technique of ART outcomes. This technique involves providing an outer sheath passage through the cervix for an inner catheter containing the embryos.
Vasectomy reversal or surgical sperm retrieval with IVF/ICSI: a decision analysis based upon age of the female partner Men with obstructive azoospermia (OA) due to prior vasectomy have two options for family building using their own gametes, vasectomy reversal (VR) or surgical sperm retrieval (SSR) followed by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). There are numerous previous decision models that have demonstrated VR to be the most cost effective strategy, but these models often do not take into account the age of the female partner, and many use an outcome measure of clinical pregnancy instead of live birth 1-3.
Is infertility diagnosis associated with embryonic mosaicism? Patients with primary infertility (PI), secondary infertility (SI), and recurrent pregnancy loss (RPL) often seek in vitro fertilization (IVF) with preimplantation genetic screening (PGS). Next-generation sequencing (NGS) is highly sensitive assay for aneuploidy and mosaicism.
Impact of patient preference on rate of double embryo transfer and resultant twin gestation Significant strides have been made in the United States to encourage single embryo transfer and minimize the occurrence and resultant risks associated with twin gestations. While the medical community has recognized the need for refinement and demonstrated the success of single embryo transfer, patient choice and education remains a significant factor in reproductive medicine and resultant obstetrical outcomes.
Abnormal cleavage patterns in embryos are associated with aneuploidy and poor morphology scores Morphokinetic parameters as measured through time-lapse imaging may predict embryonic developmental potential. While there are several studies on the timing of early cell divisions, there are limited data on abnormal cleavage (AC) events and their relationship to embryo quality. An AC is the division from a mother blastomere cell to three daughter cells. This is thought to be secondary to abnormal mitotic spindle assembly, leading to an abnormal segregation of chromosomes. Previous studies report that embryos exhibiting ACs have decreased blastulation and worse implantation rates.
High prevalence of endometriosis in patients with histologically proven adenomyosis Adenomyosis and endometriosis are conditions defined by growth of endometrial glands in the myometrium and in extra uterine tissue respectively. Both diseases cause dysmenorrhea and pelvic pain. Previous studies suggest a significant association between adenomyosis and peritoneal and deep infiltrating endometriosis in infertile women.1 2However, the prevalence of a dual diagnosis is difficult to determine secondary to the difficulty in establishing a diagnosis of adenomyosis and in differentiating between the two diseases clinically.
HMG as a treatment for unexplained recurrent early pregnancy loss About 50 percent of cases of recurrent early pregnancy loss (REPL) remain unexplained  and luteal phase insufficiency leading to defective implantation is a possible cause in some patients . Supplementing the luteal phase with progesterone therapy has not been supported by strong evidence . Basic research has shown that the corpus luteum produces at least 20 factors besides progesterone and that a properly functioning corpus luteum requires a properly functioning ovarian follicle . Consequently, the mere use of progesterone for luteal phase support may be inadequate for the treatment of these patients while stimulating the follicular phase with human menopausal gonadotropins (HMG) should result in a properly functioning corpus luteum secreting the physiological substances needed for proper implantation of the embryo.
Measurement of oxidative stress in the spent culture medium of individual embryos - a possible method for embryo selection The selection of the embryos with the best potential for implantation remains an essential quest in the field of assisted reproduction to maximize the take-home baby rate and minimize the incidence of multiple pregnancies and its associated complications. Various methods for embryo selection have been described using invasive and non-invasive procedures. However, none of these methods has confirmed its superiority over morphological selection (Gardner and Balaban, 2016). In 2011, the measurement of oxidative stress in the spent culture medium of individual embryos has been suggested as a possible method for embryo selection using the thermo-chemiluminescence (TCL) assay (Wiener-Megnazi et al, 2011).
On your feet: is sitting time linked to adverse metabolic profiles in polycystic ovary syndrome, independent of exercise? Prolonged sedentary time is associated with increased risk for cancer, type 2 diabetes and cardiovascular disease in the general population, regardless of physical activity status (1). Polycystic ovary syndrome (PCOS), a common cause of infertility, has well-established long-term metabolic risks, including type 2 diabetes, obesity, dyslipidemia, cardiovascular disease. Insulin resistance plays a central role in the pathophysiology of PCOS. Behavioral and lifestyle modifications such as diet and exercise constitute primary treatment modalities for promoting fertility and reducing long-term health risks.
ABC trial: appraisal of body content. how percent body fat (%BF) compares to body mass index (BMI) in evaluating infertile couples In IVF, implantation rate, clinical pregnancy rate, pregnancy loss rate, and live birth rate are all impacted by obesity as demonstrated by a recent investigation evaluating body mass index (BMI) and IVF outcomes in over 200,000 cycles. These data show a decrease in clinical pregnancy rate and an increase in pregnancy loss as BMI increases;1 however, BMI may not be the optimal assessment tool by which to gauge obesity. Because it is derived from an individual’s weight and height, the measurement is not sensitive to age, gender, or adiposity.
Morphokinetics of blastocyst expansion in euploid and aneuploid human embryos Identification of morphokinetic features of preimplantation human embryos that correlate with sustained ongoing implantation is a current challenge. Blastocyst biopsy has been established as one approach to selecting a single embryo for transfer after comprehensive chromosome screening (1-2). Time-lapse imaging offers a potentially complementary approach of embryo assessment by describing dynamic features of embryo development (3). Recently, morphokinetic features of human blastocyst expansion (BE) have been described for un-biopsied embryos forming sustained pregnancies (4).
Genetic testing on products of conception for spontaneous miscarriage: euploid status and prognosis for subsequent pregnancy The majority of spontaneous miscarriages are sporadic and occur as a result of genetic abnormalities. Patients with recurrent pregnancy loss often undergo cytogenetic evaluation of the products of conception to better understand etiology. While patients with recurrent pregnancy loss are often counseled that their prognosis for live birth is good, the literature does not provide data describing likelihood of subsequent conception and live birth stratified by prior aneuploid or euploid cytogenetic miscarriage.
Comparison of different protein concentrations for ICSI using sibling oocyte splits Macromolecule supplementation of culture media for human embryos is an important consideration for optimizing the culture system and laboratory outcomes. Protein used in most media serves multiple purposes, including membrane stabilization. Protein concentration may be an important consideration during procedures that disturb or disrupt the cell membrane, such as ICSI.
Does ultrasound appearance of the endometrium affect pregnancy rates in assisted reproductive technology treatment? Implantation of an embryo depends on the receptivity of endometrium. Without direct measures of receptivity, the thickness of the endometrium as well as the appearance on transvaginal ultrasound serves as surrogates for receptivity in women undergoing assisted reproductive technology (ART) treatment. The appearance most commonly seen is trilinear. Less often, it will appear semi-trilinear or unilinear. Currently in the literature there is no consensus on the relationship between the appearance of the endometrium and pregnancy rates in ART treatment.
Histopathological evaluation of placentas from pregnancies resulting from fresh versus frozen embryo transfers Frozen-thawed embryo transfer (FET) cycles appear to result in better clinical pregnancy rates and obstetrical outcomes compared to fresh ET. Controlled ovarian hyperstimulation alters the hormonal environment of the endometrium, which in theory could interfere with normal gene expression and creation of an optimal window of implantation. Abnormal placentation and impaired angiogenesis in early gestation could in turn lead to developmental programming sequelae including intrauterine growth restriction and long term health consequences for offspring.
Lactobacilli dominance on the embryo transfer catheter after euploid blastocyst transfer does not predict clinical outcomes New data suggest that a lactobacilli dominant (>90%) environment in the reproductive tract prognosticates outcomes, although this data is gleaned from the preceding cycle (1). To date, the embryo transfer data has been cultivation-dependent, a technique known to lack the ability to assess many of the dominant and major genera in the environment. Feasibility of embryo transfer catheter tip microbiome assessment has been demonstrated utilizing the unique 16S ribosomal RNA hypervariable regions to determine genus level classification (2).
Frozen embryo transfer outcomes in subsequent immediate cycles following GnRH Agonist or hCG triggers In IVF, two oocyte maturation trigger modalities are available: the more commonly used human chorionic gonadotropin (hCG) and gonadotropin releasing hormone agonists (GnRHa). GnRHa stimulates an endogenous release of gonadotropins similar to a natural surge, but the shorter duration of the surge and the pituitary down-regulation properties of the drug result in a dysfunctional and shortened luteal phase (1). Prior studies have evaluated the duration of time between stimulation and frozen-thawed embryo transfer (FET) but only one specifically after GnRHa trigger which showed equivalent pregnancy rates (2).
Pregnancy rates after euploid embryo transfer for poor responders in IVF Women with a previous or expected poor response to IVF stimulation and transfer often opt to undergo preimplantation genetic screening (PGS) in an attempt to eliminate aneuploidy as a possible cause for implantation failure or miscarriage. However, it is not clear whether PGS in poor responders suitably improves outcomes as it does in a normal or high responding couple. One study found that poor responders were less likely to achieve an embryo transfer after PGS, but those who did had similar rates of pregnancy and miscarriage (1).
Challenges associated with carrier screening in patients with history of bone marrow or stem cell transplant Current ACMG and ACOG recommendations include pan-ethnic and ethnicity-based carrier screening for couples of reproductive age. Carrier screening provides valuable information about reproductive risks for genetic conditions. However, when carrier screening is ordered on a patient who previously received a bone marrow or stem cell transplant (BMT/SCT), the results obtained may reflect the carrier status of the patient’s BM/SC donor rather than the patient’s own carrier status. This may lead to false negative or false positive results being delivered to the clinician/patient and inaccurate determination of the couple’s reproductive risks.
A predictive fertility treatment model based on oocyte quality and reactive oxygen species The spindle and chromosomal configurations are a reflection of the oocyte microenvironment. Oocyte integrity is maintained through a balance of many forces which are encompassed by the microtubule organizing center (MTOC). Alterations in this through insults can lead to subfertility. In a healthy oocyte the spindle has a symmetrical pointed barrel shape, assembled around the tightly aligned chromosomal plate at the spindle equator. Acquisition of images using confocal microscopy of the meiotic spindles and the chromosomal alignment serve as ultimate markers of oocyte quality.
Polyclonal antibody assays are better measurements of vitamin d status in asian women than monoclonal Total 25-hydroxyvitamin D [(25 (OH)D] has long been accepted as the best measure of vitamin D status. Caucasians have higher average 25 (OH)D levels than darkly pigmented ethnic groups, suggesting that certain minorities are vitamin D insufficient. It was recently discovered that vitamin D binding protein (VDBP) levels were lower in minorities resulting in higher free vitamin D, even when total vitamin D levels were low. However, these studies used a monoclonal antibody assay of VDBP that does not detect the genotypes that are more common in minority ethnic groups such as African-Americans and Asians, whereas polyclonal assays do.
Pregnancy outcomes following single versus double euploid embryo transfer Preimplantation genetic screening (PGS) has enabled our ability to screen for euploid embryos, and led to improved implantation and decreased miscarriage rates per embryo transferred. With improved embryo selection and pregnancy outcomes, the average number of embryos transferred using autologous oocytes in women <35 years old has decreased by 57% from 2004 -20141. Unfortunately, in 2014 the average number of embryos transferred was still 1.6, leading to 20-25% of the live births still being multiple gestations.
Improved pregnancy rates following transfer of euploid embryos screened by next-generation sequencing compared to array comparative genomic hybridization Preimplantation genetic screening (PGS) improves implantation and decreases miscarriage rates per embryo transferred1. PGS has evolved from fluorescence in-situ hybridization (FISH) to array comparative genomic hybridization (aCGH), and recently to next-generation sequencing (NGS). Compared to aCGH, various NGS protocols using amplified DNA have been shown to have a sensitivity and specificity as high as 100% for detecting aneuploidy in blastocysts2,3. Some NGS protocols may be able to detect partial chromosomal gains and losses and identify more cases of mosaicism within trophectoderm cells than other techniques4-6.
Utilization of a test yolk buffer solution to maintain the integrity of semen samples for an extended period of time Semen is stable at room temperature for one hour before there is a measurable decline in sperm parameters. Therefore, semen samples are collected at testing centers and readily processed. Given the time sensitive nature of the analysis, it is difficult to significantly increase laboratory volume without expanding testing hours, adding collection rooms, and/or hiring additional laboratory technicians. These issues could be overcome if the integrity of a sample could be preserved for a longer duration of time before analysis.
Sex chromosome aneuploidy is associated with younger parental ages Advanced maternal age is the most significant risk factor associated with the generation of chromosome aneuploidy in human reproduction. This directly contributes to the high burden of infertility and miscarriage associated with older reproductive age women. There is also evidence for an increase in sex chromosome aneuploidy associated with advanced paternal age and/or male factor infertility. Sex chromosome aneuploidies are observed throughout pregnancy and result in live birth, which make risk factors and detection of these anomalies critical.
Mode of progesterone administration and its effects on endometrial receptivity in programmed frozen embryo transfer cycles Pregnancy rates with frozen embryos transfers (FET) are determined by a variety of factors including embryo quality and uterine receptivity. Frozen embryos can be transferred in natural cycles, programmed cycles or a hybrid thereof. In programmed cycles, natural ovulation is suppressed with exogenous estrogen and the luteal phase is supported with progesterone. However, the effects of different preparations of progesterone on the receptivity of the endometrium have yet to be compared.
Is there more to the story than aneuploidy: uncovering factors associated with early pregnancy loss following euploid embryo transfer Advances in preimplantation genetic screening (PGS) have revolutionized the field of personalized and genomic medicine. PGS enables the clinician to select a single euploid embryo for transfer, resulting in high pregnancy rates and nearly eliminating the risk of multiple gestations. Unfortunately, PGS of embryos has not eliminated the risk of early pregnancy loss (EPL) . Published research has suggested links between the incidence of biochemical pregnancies and the presence of diminished ovarian reserve  and/or endometrial or immune factors , though the precise etiology and pathophysiology remain unclear.
Stair-step ovulation induction is not just for clomiphene citrate Letrozole has recently been shown to have superior ovulation rates over clomiphene citrate(CC) in women with polycystic ovary syndrome (PCOS).1 Some studies have noted in the absence of follicular recruitment, immediate dose escalation (stair-step method) with CC is effective to achieve ovulation and ovulation is accomplished in a shorter time frame than the traditional method. However, no studies have looked at letrozole stair-step as the first line protocol compared to this CC stair-step.
Detection of mosaicism using bayesian model Chromosomal mosaicism is a relatively common finding in IVF-derived human embryos. Mosaic embryos are characterized by the presence of more than one distinct karyotype within an embryo. Current next generation sequencing platforms do not incorporate mosaic diagnosis, however they are able to detect low levels of mosaicism within an embryo using probability and confidence level settings in their software. In general, high sensitivity mosaicism detection is associated with low specificity leading to false positives.
Using donors as their own controls in evaluating the effectiveness of fresh versus frozen oocytes Over the past decade, oocyte cryopreservation (OC) has altered the paradigm for women desiring fertility preservation either electively or for medical indications. Simultaneously, oocyte donation (OD) has gained popularity and has expanded women’s family building options. Traditionally, OD has been performed using fresh oocytes, requiring recipient/donor synchronization, which is at times significantly inconvenient for patients and health care providers. The new trend of combining OC with OD provides distinct benefits, however its effectiveness requires further research.
Variation in zona pellucida thickness between two embryos from the same cohort The zona pellucida (ZP) is a critical component of oocyte development, fertilization, and protection of the embryo prior to implantation. The ZP has been found to be associated with fertility, given that genetic mutations of the glycoproteins (ZP1-ZP4) making up the ZP have resulted in sterility . Previous literature has found an increased ZP thickness (ZPT) and decreased ZP thickness variation (ZPTV) to be associated with lower implantation rates .
Letrozole “stair-step” protocol in patients with polycystic ovary syndrome Polycystic ovarian syndrome (PCOS) is the most common cause of anovulatory infertility1. Clomiphene citrate (CC) and letrozole are commonly used oral agents to induce ovulation. A “stair-step” protocol has been described for CC in which the CC dose is increased without a progesterone withdrawal bleed2. This approach has been demonstrated to reduce time to ovulation without adverse effects 2-5. A recent double-blind, multi-center trial6 supports the use of letrozole as a first line-ovulation agent in PCOS.
Is reproductive potential compromised when embryos are re-biopsied? Genomic analysis of embryos has revolutionized reproductive medicine. Periodically, technical limitations (allele drop-out, DNA amplification failure, etc.) may generate inconclusive or non-diagnostic results. In these instances, embryos can be thawed to undergo a second biopsy to ascertain ploidy status.
Diminished ovarian reserve may explain otherwise unexplained recurrent pregnancy loss The majority of patients undergoing ASRM evaluation for recurrent pregnancy loss (RPL) will remain undiagnosed (1). It is well known the majority of first trimester miscarriages are due to aneuploidy in the embryo (2) and the risk of aneuploidy increases with diminished ovarian reserve (DOR) (3, 4). In this study we investigate the possible link between DOR and unexplained RPL.
Embryonic mosaicism: defining prevalence in terms of clinical relevance Chromosomal mosaicism, the presence of two or more cell lines in human preimplantation embryos, has conceived a new complexity for clinicians in the fields of IVF and PGS alike. The exact prevalence of mosaicism and the reproductive potential of each individually diagnosed mosaic embryo remains unknown. Various outcomes associated with the transfer of mosaic embryos include failed implantation, miscarriage, healthy live birth, or live birth with defects. By defining the prevalence of mosaicism based on clinical significance, we can potentially improve the reporting of mosaic embryos and help clinicians and patients understand what a mosaic result means for the long-term potential of the embryo.
Is a viable fetus in a vanishing twin before demise associated with obstetrical outcomes of the surviving twin? The adverse association of vanishing twin (VT) on birth weight of the surviving twin has been attributed to increasing gestational age (GA) at the time of vanishing (1,2). However, to our knowledge no study has investigated whether this association is related to the presence of a viable fetus in the VT before demise. It is also unknown whether IVF treatment modality or any patient demographic is associated with an increased incidence of VT.
Prediction of a reciprocal translocation by preimplantation genetic screening (PGS) An estimated 1/500 individuals carry a balanced chromosome rearrangement, and this frequency may be as high as 1/100 in the IVF patient population. Balanced translocations typically have no impact on an individual’s health; however, the transmission of unbalanced translocations can cause infertility and miscarriage. Karyotyping is routinely performed for a patient with a history of multiple pregnancy losses, but is not part of the standard workup for the unselected infertility patient. We hypothesize that patterns of segmental aneuploidies found in PGS results can predict a maternal or paternal balanced translocation.
Preliminary study to investigate telomerase reverse transcriptase expression among human cumulus cells Telomerase reverse transcriptase (hTERT) is a subunit of the enzyme telomerase, which is responsible for lengthening telomeres in DNA and a critical contributor to chromosome stability during cell replication. Lack of telomerase activity in somatic cells results in cell senescence once the telomeres shorten below a critical threshold. Cumulus cells surround the developing oocyte during follicle growth and maturation and are responsible for maintaining pH and meeting the metabolic needs of developing oocyte.
Concurrent genome and transcriptome analysis from a single trophectoderm biopsy Trophectoderm biopsy and subsequent DNA-sequencing has been used clinically to study the genome of human embryos, particularly for characterizing embryo ploidy. RNA-sequencing after trophectoderm biopsy has been used in research settings, but traditionally multiple biopsies have been required for concurrent genome and transcriptome analysis. Consequently, concerns regarding the effect of multiple biopsies on clinical embryos have precluded application of RNA analysis in the clinical setting.
CAREs trial: celiac disease and reproductive effects Celiac disease is a systemic autoimmune disease that occurs in genetically susceptible patients and is provoked by the ingestion of gluten. This chronic disease has both intestinal and extra-intestinal manifestations. One extra-intestinal manifestation of celiac disease is infertility or subfertility, though the prevalence if disease in the infertile population in unknown, and the anticipated improvement gained from a gluten free diet has not yet been demonstrated.
Distinct microrna suggest differential gene regulation in granulosa cells in young women with normal ovarian reserve compared to YOUNG WOMEN WITH Diminished ovarian reserve Folliculogenesis, the process through which primordial follicles develop into pre-ovulatory follicles enclosing a mature oocyte, hinges on a complex communication between the oocyte and its neighboring follicular cells. Cumulus cells (CC) envelope the oocyte with the inner layer having direct communication across the zona pellucida, while the mural granulosa cells (GC) are separated from the oocyte by CC and the fluid-filled antral cavity. Recently, microRNA (miRNA), small endogenous noncoding RNAs (∼21nucleotides) have been identified as important post-transcriptional gene regulators present in both GCs and CCs and are packaged into extracellular vesicles with potential to act as a vehicle for cross talk between GCs, CCs, and the oocyte.
Impaired autophagy contributes to obese patients decreased ability to undergo in vitro decidualization Endometrial Stromal Cell (ESC) decidualization is the process in which ESCs undergo morphologic and functional change in order to differentiate into decidual cells and become receptive to embryonic implantation. Defective decidualization can lead to infertility and poor pregnancy outcomes. Autophagy is the catabolic process of intracellular recycling and has been shown to be defective in obese tissue. We have previously shown in our lab that obese women (BMI ≥ 30) have impaired ability to undergo in vitro decidualization compared to lean women.
Cyclophosphamide and its metabolite impact on fertilization through mitochondrial dysfunction Cyclophosphamide (CP) is a chemotherapeutic drug with a wide range of applications ranging from treatment of many gynecological cancers to various autoimmune diseases. As a sequela of CP exposure many women suffer from premature ovarian insufficiency and infertility. CP is metabolized in the liver to give stable toxic compound acrolein. Recently, we have established that CP and acrolein exposure causes deterioration of oocyte quality through changes in microtubule morphology and chromosomal alignment.
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