Fertility

MedicalResearch.com Interview with: [caption id="attachment_29707" align="alignleft" width="144"]David McLernon PhD MPhil BSc Research Fellow in Medical Statistics Medical Statistics Team Institute of Applied Health Sciences University of Aberdeen Foresterhill Aberdeen Dr. David McLernon[/caption] David McLernon PhD MPhil BSc Research Fellow in Medical Statistics Medical Statistics Team Institute of Applied Health Sciences University of Aberdeen Foresterhill Aberdeen MedicalResearch.com: What is the background for this study? Response: Normally when a couple attend a fertility clinic to begin IVF treatment they are only informed about their chances of having a baby for the first attempt of IVF. In actual fact the first treatment is often unsuccessful and many couples will go on to have several complete cycles of the treatment– each involving the transfer of one or two fresh embryos potentially followed by one or more frozen embryo transfers. We felt that a prediction model that could calculate the chances of having a baby over the complete package of treatment would provide better information for couples.

MedicalResearch.com Interview with: [caption id="attachment_29039" align="alignleft" width="120"]Kavita Vedhara FAcSS Professor of Health Psychology Division of Primary Care School of Medicine University Park,N ottingham Prof. Kavita Vedhara[/caption] Kavita Vedhara FAcSS Professor of Health Psychology Division of Primary Care School of Medicine University Park,Nottingham MedicalResearch.com: What is the background for this study? What are the main findings? Response: There has been a longstanding interest in the role of the hormone cortisol in fertility, because of its potential to affect the functioning of the biological systems that influence both conception and pregnancy. This interest has extended to IVF, with researchers exploring the relationship between levels of the hormone and pregnancy since the advent of the treatment in the late 1970s. However, a recent review showed that the relationship between cortisol and pregnancy in IVF was unclear. A number of reasons were highlighted for this, including that all of the studies to date had relied on short-term measures of the hormone measured in blood, saliva, urine and sometimes follicular fluid. Such measures can only capture hormone levels over a matter of minutes and hours. Such ‘snapshots’ are unable to give us an accurate picture of the levels of hormone over longer periods of time. This is important because any clinically relevant effects of cortisol on fertility are only likely to occur in the context of long-term changes in the hormone. In recent years it has become possible to measure long-term levels of cortisol in hair. Cortisol is deposited in the hair shaft and because human hair grows, on average, 1cm per month, a 3cm sample of hair closest to the scalp can tell us about levels of cortisol in the previous 3 months. We used the development of this technique to examine whether long term levels of cortisol (as measured in hair), or short term levels of cortisol (as measured in saliva) could predict whether or not women going through IVF would become pregnant. If you are trying to obtain a perfect cortisol balance, I use this product that helps to do just that.

MedicalResearch.com Interview with: Anders Rehfeld MD, PhD Student Faculty of Health and Medical Sciences Department of Cellular and Molecular Medicine University of Copenhagen Copenhagen Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: Human fertility is declining in many areas of the world and the reason is largely unknown. Our study shows that 44% of the tested chemical UV filters can induce calcium signals in human sperm cells, thereby mimicking the effect of progesterone. Progesterone-induced calcium signals, and the sperm functions it triggers, is absolutely essential for the human sperm cell to normally fertilise the human egg.

MedicalResearch.com Interview with: [caption id="attachment_27272" align="alignleft" width="150"]Peter Sutovsky PhD Professor of Animal Science in the College of Agriculture, Food and Natural Resources University of Missouri Professor of Obstetrics, Gynecology and Women’s Health at the School of Medicine University of Missouri Health System Dr. Peter Sutovsky[/caption] Peter Sutovsky PhD Professor of Animal Science in the College of Agriculture, Food and Natural Resources University of Missouri Professor of Obstetrics, Gynecology and Women’s Health at the School of Medicine University of Missouri Health System MedicalResearch.com: What is the background for this study? What are the main findings? Response: Strictly maternal inheritance of mitochondria, the cellular power stations, and mitochondrial genes that mitochondria harbor, is a major biological paradigm in mammals. Propagation of paternal, sperm-contributed mitochondrial genes, resulting in a condition called heteroplasmy, is seldom observed in mammals, due to post-fertilization elimination sperm mitochondria, referred to as “sperm mitophagy.” Our and others’ recent results suggest that this process is mediated by the synergy of ubiquitin–proteasome system (UPS) pathway that recycles outlived cellular proteins one molecule at a time, and autophagic pathway capable of engulfing and digesting an entire mitochondrion. Here we demonstrate that the co-inhibition of the ubiquitin-binding autophagy receptor proteins SQSTM1, GABARAP, and UPS, and the UPS protein VCP dependent pathways delayed the digestion of sperm mitochondria inside the fertilized pig egg. By manipulating said proteins, we created heteroplasmic pig embryos with both the paternal and maternal mitochondrial genes. Such animal embryos that could be used as a biomedical model to research and alleviate certain forms of mitochondrial disease.

MedicalResearch.com Interview with: [caption id="attachment_26343" align="alignleft" width="174"]Alexandra W. van den Belt-Dusebout, PhD Department of Epidemiology The Netherlands Cancer Institute The Netherlands Dr. Alexandra van den Belt-Dusebout[/caption] Alexandra W. van den Belt-Dusebout, PhD Department of Epidemiology The Netherlands Cancer Institute The Netherlands MedicalResearch.com: What is the background for this study? Response: In vitro fertilization (IVF) is commonly used, but because of the relatively recent use of IVF, long-term breast cancer risk is not yet known. Female sex hormones have been shown to affect breast cancer risk. Because sex hormone levels during hormonal stimulation of the ovaries for IVF are up to 10 times higher than in natural cycles, IVF was expected to increase breast cancer risk.

MedicalResearch.com Interview with: [caption id="attachment_26136" align="alignleft" width="149"]Dejan R. Nonato, MD, PhD Institute of Tropical Pathology and Public Health School of Medicine Federal University of Goiás Goiânia, GO, Brazil Dr. Dejan Nonato[/caption] Dejan R. Nonato, MD, PhD Institute of Tropical Pathology and Public Health School of Medicine Federal University of Goiás Goiânia, GO, Brazil MedicalResearch.com: What is the background for this study? Response: Human papillomavirus (HPV) and Chlamydia trachomatis (CT) share the same route of sexual transmission and possess similar risk factors, indicating that co-infection may act synergistically in the induction of epithelial cell abnormalities.

MedicalResearch.com Interview with: [caption id="attachment_25933" align="alignleft" width="180"]Roberta Rizzo PhD Department of Medical Sciences Section of Microbiology University of Ferrara Ferrara, Italy Dr. Roberto Rizzo[/caption] Roberta Rizzo PhD Department of Medical Sciences Section of Microbiology University of Ferrara Ferrara, Italy MedicalResearch.com: What is the background for this study? Response: Infertility affects approximately 6% of 15-44 year old women or 1.5 million women in the US, according to the CDC. Approximately 25% of female infertility cases are unexplained, leaving women with few options other than expensive fertility treatments. Researchers are trying to identify factors and mechanisms at the basis of this condition.

MedicalResearch.com Interview with: [caption id="attachment_25803" align="alignleft" width="107"]Jessica Datta Department of Social & Environmental Health Research London School of Hygiene & Tropical Medicine London Jessica Datta[/caption] Jessica Datta Department of Social & Environmental Health Research London School of Hygiene & Tropical Medicine London MedicalResearch.com: What is the background for this study? Response: The paper presents an analysis of data from the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3). Natsal-3 is a survey of more than 15,000 women and men aged 16-74 resident in Britain, conducted in 2010-2012, which includes a wide range of questions about sexual relationships and behaviour and reproductive history. In this paper we analysed responses to the questions: ‘Have you ever had a time, lasting 12 months or longer, when you and a partner were trying for a pregnancy but it didn’t happen?’ and ‘Have you (or a partner) ever sought medical or professional help about infertility?’. As well as calculating the prevalence of experience of infertility and help seeking, we looked at associated factors e.g. education, employment, relationship status.

[caption id="attachment_25318" align="alignleft" width="160"]MedicalResearch.com Interview with: Ghenet Besera, MPH National Center for Chronic Disease Prevention and Health Promotion CDC MedicalResearch.com: What is the background for this study? Response: The Title X program, established in 1970, offers confidential family planning and related preventive services to both men and women. While most clients are women, Title X also promotes use of services by men through delivery of male-focused services. Men’s family planning needs include services not only relate to contraception, but also relate to preconception care, infertility, and STD/ HIV services, which affect their reproductive health and overall health. MedicalResearch.com: What are the main findings? Response: More men are visiting Title X Family Planning Program sites. From 2003-2014, a total of nearly 4 million men visited Title X service sites in the 50 states and District of Columbia. The percent of male clients nearly doubled from 4.5 percent in 2003 to 8.8 percent in 2014. The percentage of clients that were male also varied widely from state to state, from 1 percent or less in Tennessee, Mississippi, and Alabama to 27.2 percent in the District of Columbia. MedicalResearch.com: What should readers take away from your report? Response: The finding that more men are seeking these services at Title X sites is encouraging, especially given the opportunity to offer related preventive services at the family planning visit. More men are accessing services related to family planning, achieving pregnancy when desired, and services that can affect their overall health, such as preventing or addressing sexually transmitted infections. MedicalResearch.com: What recommendations do you have for future research as a result of this study? Response: Future research could examine men’s receipt of sexual and reproductive health services in other health care settings. This would be important to assess to see if the increase in males seeking family planning services at Title X clinics, is true for other healthcare settings. MedicalResearch.com: Is there anything else you would like to add? Response: In 2014, CDC and OPA published Providing Quality Family Planning Services: Recommendations of CDC and the U.S. Office of Population Affairs, which describes services that should be offered in a family planning visit, and guidance for providing those services to both men and women. Health care providers can adopt the framework used by Title X clinics to better provide family planning and related preventive health services to men. MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community. Citation: Besera G, Moskosky S, Pazol K, et al. Male Attendance at Title X Family Planning Clinics — United States, 2003–2014. MMWR Morb Mortal Wkly Rep 2016;65:602–605. DOI: http://dx.doi.org/10.15585/mmwr.mm6523a3. Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions. More Medical Research Interviews on MedicalResearch.com Ghenet Besera[/caption] MedicalResearch.com Interview with: Ghenet Besera, MPH National Center for Chronic Disease Prevention and Health Promotion CDC MedicalResearch.com: What is the background for this study? Response: The Title X program, established in 1970, offers confidential family planning and related preventive services to both men and women. While most clients are women, Title X also promotes use of services by men through delivery of male-focused services. Men’s family planning needs include services not only related to contraception, but also related to preconception care, infertility, and STD/ HIV services, which affect their reproductive health and overall health.

MedicalResearch.com Interview with: [caption id="attachment_24730" align="alignleft" width="92"] Dr. Stacey Missmer[/caption] Stacey A. Missmer, ScD Associate Professor of Obstetrics, Gynecology, and Reproductive Biology Director of Epidemiologic Research, Division of Reproductive Medicine Scientific Director, Boston Center for Endometriosis Brigham and Women’s Hospital and Harvard Medical School Associate Professor in Epidemiology Harvard T.H. Chan School of Public Health MedicalResearch.com: What is the...

MedicalResearch.com Interview with: [caption id="attachment_24169" align="alignleft" width="200"]Dr. Scott Sills MD, PhD Medical Director at the Center for Advanced Genetics an IVF program based in Carlsbad, California Dr. E. Scott Sills[/caption] Dr. Scott Sills MD, PhD Medical Director at the Center for Advanced Genetics an IVF program based in Carlsbad, California  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Sills: Often regarded as a miracle procedure by many infertile couples, in vitro fertilization (IVF) can be financially difficult for those without insurance coverage for the treatment. This prohibitive cost leads many would-be parents who pursue IVF to transfer multiple embryos at once, to increase their chances of getting a baby and minimize the need for additional attempts. This new study now reports that the economic impact of IVF deserves a closer look. As corresponding author E. Scott Sills, MD PhD noted, rates of cesarean-section deliveries, premature births, and low birth weight of babies are all greater with two or more embryos transferred to the mother at once, compared to a lower risk, single-embryo pregnancy. The data derived from a comprehensive analysis of all IVF cases in Vermont (UVM) and was recently published in the journal Applied Health Economics & Health Policy. It is believed to be the first effort to calculate the difference in infant hospital costs based on the number of embryos transferred. Sills and his team had access to UVM Medical Center records of patients who conceived through IVF and delivered at least 20 weeks into their pregnancies between 2007 and 2011.

MedicalResearch.com Interview with: [caption id="attachment_23611" align="alignleft" width="180"]Paola Grimaldi, PhD Associate Professor of Anatomy Department of Biomedicine and Prevention, School of Medicine, University of Rome Tor Vergata Rome, Italy Dr. Paola Grimaldi[/caption] Paola Grimaldi, PhD Associate Professor of Anatomy Department of Biomedicine and Prevention, School of Medicine, University of Rome Tor Vergata Rome, Italy MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Grimaldi: Our previous studies reported that mouse mitotic germ cells, spermatogonia, express type 2 cannabinoid receptor (CB2) and its stimulation promoted differentiation and meiotic entry of these cells in vitro. In this study we demonstrate that CB2 plays a role of in regulating the correct progression of spermatogenesis in vivo and we found that the use of exogenous agonist or antagonist of this receptor disrupts the normal differentiation of germ cells. This suggests that a basal and finely regulated level of endocannabinoids in male germ cells activate CB2, thus maintaining the homeostasis of spermatogenesis. Another important novelty of our study is that CB2 activation in developing germ cells determines the appearance of modifications in DNA-bound proteins, which are known to impact on gene expression and inheritance of specific traits in developing germ cells. An exciting idea could be that these modifications might be maintained in the mature spermatozoa and transmitted to the offspring.

MedicalResearch.com Interview with: [caption id="attachment_23481" align="alignleft" width="100"]Dr. Kieron Barclay PhD Department of Social Policy London School of Economics Dr. Barclay[/caption] Dr. Kieron Barclay PhD Department of Social Policy London School of Economics MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Barclay: Mean age at childbearing has been increasing in most countries in the OECD since the early 1970s. A wealth of research has shown that childbearing at advanced ages is associated with greater difficulty in terms of getting pregnant, higher rates of miscarriage, stillbirth, and increased risk of poor peri-natal outcomes such as pre-term birth and low birth weight. Studies also indicate that the offspring of older mothers have a greater risk of Alzheimer’s disease, diabetes, and mortality in adulthood. However, from the perspective of any individual woman, delaying childbearing to an older age necessarily also means that she will give birth in a later birth year. The last 40 to 50 years have seen substantial improvements in educational opportunities, and better public health conditions and medical knowledge. As a result, these positive secular trends may outweigh or counterbalance the negative effects of reproductive aging for the child.

MedicalResearch.com Interview with: [caption id="attachment_23484" align="alignleft" width="200"]Frida Lundberg | PhD Student Dept. of Medical Epidemiology and Biostatistics Karolinska Institutet Frida Lundberg[/caption] Frida Lundberg | PhD Student Dept. of Medical Epidemiology and Biostatistics Karolinska Institutet Medical Research: What is the background for this study? Response: Fertility treatments involve stimulation with potent hormonal drugs that increase the amount of the sex hormones estrogen and progesterone. These hormones have been linked to breast cancer risk. Further, as these treatments are relatively new, most women who have gone through them are still below the age at which breast cancer is usually diagnosed. Therefore we wanted to investigate if infertility and fertility treatments influences mammographic breast density, a strong marker for breast cancer risk that is also hormone-responsive. Medical Research: What are the main findings? Response: We found that women with a history of infertility had higher absolute dense volume than other women. Among the infertile women, those who had gone through controlled ovarian stimulation (COS) had the highest absolute dense volume. The results from our study indicate that infertile women, especially those who undergo COS, might represent a group with an increased risk of breast cancer. However, the observed difference in dense volume was relatively small and has only been linked to a modest increase in breast cancer risk in previous studies.  As the infertility type could influence what treatment the couples undergo, the association might also be due to the underlying infertility rather than the treatment per se.

MedicalResearch.com Interview with: [caption id="attachment_23288" align="alignleft" width="200"]Marcelo L. Urquia PhD, MSc, Mg Public Health, BA Scientist, Li Ka Shing Knowledge Institute St. Michael’s Hospital Assistant Professor, Dalla Lana School of Public Health, University of Toronto Dr. Marcelo Urquia[/caption] Marcelo L. Urquia PhD PhD, MSc, Mg Public Health, BA Scientist, Li Ka Shing Knowledge Institute St. Michael’s Hospital Assistant Professor, Dalla Lana School of Public Health, University of Toronto  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Urquia: In most populations the sex ratio at birth, that is, ratio of male newborns to female newborns, is about 103 to 107 males per 100 females. This is well established and does not substantially vary according to whether a woman had one or two previous children of the same sex, as each pregnancy is an independent event. However, it is known that several parts of Asia characterize for having son-biased sex ratios at birth. As countries from Asia, such as India and China are the top contributors of births to immigrant women in Canada, we wanted to verify whether son-biased sex ratios were present in Canada. Since induced abortion following prenatal sex determination using ultrasonography has been hypothesized to be a major mechanism that may explain the distorted sex ratios observed in Asia, we also studied the connection between the probability of having boys after induced abortions. In our first study entitled “Sex ratios after induced abortion” published in CMAJ (http://www.cmaj.ca/lookup/doi/10.1503/cmaj.151074), which used Ontario health care records, we found that sex ratios among Canadian-born women in Ontario were within the expected, irrespective of birth order. The sex ratio among immigrant women from India with two prior girls was 196 males per 100 females for the third live birth. Among Indian immigrant women with two prior daughters the sex ratio increased to 326 males per 100 females if they have had induced abortions preceding the third birth, to 409 males per 100 females if they have had more than one induced abortion since the last newborn child, and to 663 males per 100 females if they have had at least one preceding abortion after 14 weeks of gestation (when the sex of the fetus can be accurately estimated by ultrasonography). These findings suggest that among Indian immigrants to Ontario induced abortions of female fetuses are much more common than induced abortions of male fetuses, which helps explain the deficit in the expected number of female newborns. In our companion paper entitled “Variations in male-female infant ratios among births toCanadian- and Indian-born mothers, 1990-2011: a population-based register study” and published in CMAJ Open (insert URL), we used national birth certificate data and verified that the patterns observed in Ontario are very likely to apply to all Canadian provinces. Moreover, son-biased sex ratios at birth among Indian immigrants have existed in Canada since the early 1990’s. The deficit in the expected number of girls to Indian immigrants over the last two decades in Canada is in between 3211 to 5921.

MedicalResearch.com Interview with: [caption id="attachment_23050" align="alignleft" width="100"]Sheree L. Boulet, DrPH, MPH Division of Reproductive Health Centers for Disease Control and Prevention Atlanta, Georgia Dr. Sheree Boulet[/caption] Sheree L. Boulet, DrPH, MPH Division of Reproductive Health Centers for Disease Control and Prevention Atlanta, Georgia MedicalResearch.com: What is the background for this study? Dr. Boulet: Findings from some studies have suggested that children conceived with assisted reproductive technology (ART) have increased risks of birth defects compared with spontaneously conceived children. Many of these studies were limited by a small sample size and were unable to assess risks associated with specific ART procedures. MedicalResearch.com: What are the main findings? Dr. Boulet: We found that singleton infants conceived using assisted reproductive technology were 1.4 times more likely to have a non-chromosomal birth defect compared with other infants, and the risks were highest for gastrointestinal and musculoskeletal defects. However, when our study was restricted to only ART-conceived infants, no single procedure substantially increased the risk for birth defects. This suggests that the higher risk of birth defects may be due to underlying issues related to infertility, rather than to ART itself.

MedicalResearch.com Interview with: Anders Rehfeld MD, PhD Student University of Copenhagen Faculty of Health and Medical Sciences Department of Cellular and Molecular Medicine Copenhagen, Denmark MedicalResearch.com: What is the background for this study? What are the main findings? DrRehfeld: Human fertility is declining in many areas of the world and the reason is largely unknown. Our study shows that 44% tested chemical UV filters can induce calcium signals in human sperm cells, thereby mimicking the effect of progesterone and possibly interfering with the fertilizing ability of human sperm cells. Progesterone-induced calcium signaling, and the sperm functions it triggers, is absolutely essential for the human sperm cell to normally fertilize the human egg.

MedicalResearch.com Interview with: [caption id="attachment_22896" align="alignleft" width="175"] Dr. Eric Chow[/caption] Eric J. Chow, MD, MPH Hematology-Oncology Attending physician, Seattle Childrens Hospital Assistant professor of Pediatrics, University of Washington School of Medicine Member of the Clinical Research and Public Health Sciences Divisions Fred Hutchinson Cancer Research Center  MedicalResearch.com: What is the background for this study? Dr. Chow: Adverse effects on...

MedicalResearch.com Interview with: Melissa Miller, PhD Postdoctoral fellow at both UC Berkeley and UC San Francisco  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Miller: This work builds on years of observed, but unexplained, phenomena within sperm cells which respond almost instantaneously to the presence of the steroid hormone progesterone. Typically, steroid signaling occurs through a long, slow process that involves the modification of gene amount within a cell. However, there is an alternative mechanism that is not well understood that works differently and is termed non-genomic progesterone signaling. We found that progesterone in human sperm cells binds to a protein called ABHD2 and activates its activity to clear the cell of the endogenous cannabinoid 2AG.  2AG is an inhibitor of sperm activation and its removal from the cellular membrane allows the sperm cells to change its motility so that it may reach and fertilize the egg. Men who’s sperm is unable to undergo this progesterone activated motility change are infertile.

MedicalResearch.com Interview with: [caption id="attachment_22845" align="alignleft" width="133"]Germaine M. Buck Louis, Ph.D., M.S. Office of the Director, Division of Intramural Population Health Research Eunice Kennedy Shriver National Institute of Child Health and Human Development Rockville, Maryland 20852. Dr-Germaine M. Buck-Louis[/caption] Germaine M. Buck Louis, Ph.D., M.S. Office of the Director Division of Intramural Population Health Research Eunice Kennedy Shriver National Institute of Child Health and Human Development Rockville, Maryland 20852. MedicalResearch.com: What is the background for this study? What are the main findings? Response: To understand the association between couples’ lifestyles and risk of pregnancy loss.  Couples were recruited upon discontinuing contraception to try for pregnancy and followed daily for up to one year of trying or until pregnancy.  Pregnant women were followed daily for 7 weeks following conception then monthly.

[caption id="attachment_19488" align="alignleft" width="145"]Kutluk Oktay, MD, PhD. Professor of Obstetrics & Gynecology, Medicine, and Cell Biology & Anatomy Director, Division of Reproductive Medicine & Institute for Fertility Preservation Innovation Institute for Fertility and In Vitro Fertilization New York Medical College, Valhalla, NY Dr. Oktay[/caption] MedicalResearch.com Interview with: Kutluk Oktay, MD, PhD. Professor of Obstetrics & Gynecology, Medicine, and Cell Biology & Anatomy Director, Division of Reproductive Medicine & Institute for Fertility Preservation Innovation Institute for Fertility and In Vitro Fertilization New York Medical College, Valhalla, NY Medical Research: What is the background for this study? What are the main findings? Dr. Oktay: Cancer treatments cause infertility and early menopause in a growing number of young women around the world and US. One of the strategies to preserve fertility, which was developed by our team, is to cryopreserve ovarian tissue before chemotherapy and later transplant it back to the patient when they are cured of the cancer and ready to have children. However, success of ovarian transplantation has been limited due to limitation in blood flow to grafts. In this study we described a new approach which seems to improve graft function. The utility of an extracellular tissue matrix and robotic surgery seems to enhance graft function. With this approach both patients conceived with frozen embryos to spare and one has already delivered.

[caption id="attachment_19086" align="alignleft" width="150"]Dr. Norbert Gleicher, MD, FACOG, FACS Founder, Center for Human Reproduction Dr. Gleicher[/caption] MedicalResearch.com Interview with Dr. Norbert Gleicher, MD, FACOG, FACS Founder, Center for Human Reproduction Background: What’s My Fertility and the Center for Human Reproduction in New York, have announced the first screening for Premature Ovarian Aging (POA) in young women, based on new research that the FMR1 gene can be predictive of POA. Medical Research:   What is Premature Ovarian Aging (POA)? How does POA differ from Premature Ovarian Failure? Dr. Gleicher: Premature Ovarian Aging (POA) is a condition that causes a young woman’s ovaries to age faster than normal. It affects roughly 10% of all women, regardless of race or ethnic background. POA typically causes no symptoms until the ovarian reserve is already very low. Women are born with all their egg cells (called oocytes). Scientists refer to this as a woman’s original “ovarian reserve.” From birth on, significant numbers of these eggs are constantly lost until menopause. As women age, their ovarian reserve, therefore, depletes and fertility declines. In most women, fertility begins to decline around age 35 – but for women at risk for POA, fertility declines can begin as early as in their teens or 20s. POA in early stages typically has no symptoms. Most women until now, therefore, are usually only diagnosed after troubles conceiving become apparent, which brings them to a fertility specialist. At that point, most require stressful and costly infertility treatment to have children. Premature Ovarian Failure (POF), sometimes also called premature menopause of primary ovarian insufficiency (POI) is the end stage of POA, when women reach menopause under age 40. Fortunately, this happens only to 10% of the 10% of women with Premature Ovarian Aging, - which means to 1% of the total female population. In those unfortunate few, even routine IVF can usually no longer help, and most of these women will only conceive with use of young donor eggs. 

Rajiv McCoy, PhD Dept. of Genome Sciences Univ. of WashingtonMedicalResearch.com Interview with: Rajiv McCoy, PhD Dept. of Genome Sciences Univ. of Washington Medical Research: What is the background for this study? What are the main findings? Dr. McCoy:  Aneuploidy—the inheritance of extra or missing chromosomes compared to the typical 46-chromosome set—is extremely common in human embryos. The vast majority of aneuploidies result in preclinical pregnancy loss, often before the pregnancy is even recognized by the mother. This is thought to be the primary reason why only ~30% of all conceptions result in successful live birth. Many aneuploidies arise during egg formation, with the frequency increasing with maternal age. In addition to meiotic errors, a large proportion of aneuploidies affecting cleavage-stage embryos are mitotic in origin, arising during the initial post-fertilization cell divisions. These initial divisions are controlled by machinery contributed by the mother in the egg (before the embryo's genome has been activated). While these mitotic errors are frequent in cleavage-stage embryos, we found that they are rare in embryos at day-5 of development (the blastocyst stage), suggesting that embryos and/or cells with extensive mitotic errors do not survive to day 5. We discovered that some women have a greater propensity to produce embryos with mitotic errors than others, and our idea was that maybe differences in the mitotic machinery could help explain this. Using data from in vitro fertilized embryos screened by our collaborators at Natera, we found that women who have a particular version of a gene called PLK4 tend to produce more aneuploid embryos, regardless of age. This genetic variant is actually very common—more than half of people carry at least one copy—and is present in nearly all populations. PLK4 has a well-known role in ensuring the proper distribution of chromosomes. We also found that patients referred for embryo screening due to previous IVF failure had higher rates of mitotic error, which underscores the clinical importance of this form of whole-chromosome abnormality.

Audrey J. Gaskins, Sc.D. Postdoctoral Fellow Department of Nutrition Harvard T.H. Chan School of Public Health Boston, MA 02115 MedicalResearch.com Interview with: Audrey J. Gaskins, Sc.D.  Postdoctoral Fellow Department  of Nutrition Harvard T.H. Chan School of Public Health Boston, MA 02115     Medical Research: What is the background for this study? What are the main findings? Dr. Gaskins: Infertility, defined as the inability to conceive after 12 months of unprotected intercourse, is a common reproductive disorder affecting ~15% of couples who attempt to become pregnant. Assisted reproductive technologies (ART), which include in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI), have become the main treatment modalities for couples facing infertility. Pre-conceptional folate and vitamin B12 have been linked to many beneficial early pregnancy outcomes among couples undergoing assisted reproductive technologies treatment in Europe but mixed results have been found in regards to clinical pregnancy and live birth rates. Therefore, we sought to investigate whether higher levels of serum folate and vitamin B12 could increase reproductive success in a cohort of women undergoing assisted reproductive technologies at an academic medial center in the United States. We found that high concentrations of folate and vitamin B12 in serum are associated with increased chance of live birth following assisted reproduction. Moreover, women with higher concentrations of both serum folate and vitamin B12 had the greatest likelihood of reproductive success. Analysis of intermediate endpoints suggests that folate and vitamin B12 may exert their favorable effects on pregnancy maintenance following implantation.

MedicalResearch.com Interview with: Camilla Sandal Sejbaek PhD Department of Public Health University of Copenhagen Medical Research: What is the background for this study? What are the main findings? Response: Previous literature have shown ambiguous results when investigating the association between becoming a mother and depression among women in fertility treatment. Small questionnaire-based studies with self-reported depression have shown that women in unsuccessful fertility treatment had a higher risk of depressive symptoms compared to women in successful fertility treatment. Two larger register-based studies using clinical depression (depression diagnosed at the psychiatric hospitals) have shown that women becoming a mother are at increased risk of clinical depression. Our findings, from a large register-based study with about 41,000 women in assisted reproductive technology (ART) treatment, showed that women WHO became mothers had a higher risk of clinical depression compared to women in ART treatment WHO did not become mothers. The risk of clinical depression were more than five-fold higher within the first 6 weeks after becoming a mother to a live-born child.

Vitaly A Kushnir MD The Center for Human Reproduction New York, NY 10021MedicalResearch.com Interview with: Vitaly A Kushnir MD The Center for Human Reproduction New York, NY 10021 Medical Research: What is the background for this study? What are the main findings? Dr. Kushnir: In January 2013, the American Society for Reproductive Medicine declared the technique of oocyte cryopreservation no longer experimental, although they body did call for further study. Vitaly A. Kushnir, M.D., of the Center for Human Reproduction, and colleagues used 2013 data from 380 U.S fertility centers to compare live birth and cycle cancellation rates using either fresh or cryopreserved donor oocytes. The study found roughly 20 percent of donor cycles used cryopreserved oocytes and 80 percent fresh oocytes. Of those embryos transferred, 56 percent that started as fresh oocytes resulted in live births compared to just 47 percent of those that started as cryopreserved oocytes.

Prof. Dr. med. Christian F. Poets Neonatologie, Univ.-Klinikum Tübingen Tübingen GermanyMedicalResearch.com Interview with: Prof. Dr. med. Christian F. Poets Neonatologie, Univ.-Klinikum Tübingen Tübingen Germany Medical Research: What is the background for this study? Prof. Poets: Episodes of intermittent hypoxemia (lack of oxygen) and bradycardia (slow heart rate) are common in very preterm infants and often a subject of considerable concern. However, up to now there has been a lack of knowledge as to how often or how long such episodes may occur without increasing an infant’s risk for impaired development or even death. In this study, we utilized long-term recordings (lasting 8-12 weeks) of oxygen saturation and heart rate obtained as part of the Canadian Oxygen Trial (COT), a large study performed in extremely immature infants and comparing a higher with a lower oxygen saturation target range (85-89 vs. 91-95% oxygen saturation measured by pulse oximetry). For this secondary analysis, we wanted to test the hypotheses that spending a high proportion of time at an oxygen saturation below 80% or a pulse rate <80 beats per minute increases the risk of the following adverse outcomes:
  1. Death after reaching a post-menstrual age of 36 weeks (i.e. 4 weeks before their due date) or disability, determined at 18-22 months corrected age and defined as motor impairment, cognitive or language delay, severe hearing loss, or bilateral blindness;
  2. Motor impairment (determined at 18-22 months corrected age);
  3. Cognitive or language delay (determined at 18-22 months corrected age);
  4. Severe retinopathy of prematurity.
Medical Research: What are the main findings? Prof. Poets: Analyzable recordings and outcome data were available for 1019 infants, of which the least affected 10% spent 0.4%, and the most affected infants 13.5% of the time at an oxygen saturation <80%. We found that the risk to develop all of the adverse outcomes mentioned above increased with the percentage of time spent at an oxygen saturation below 80%, but this was true only for hypoxemic events lasting for at least 1 minute. Episodes with a low heart rate (in the absence of concomitant hypoxemia) were not associated with an increased risk of an adverse outcome. Interestingly, hypoxemic events occurring in infants originally randomized to the higher oxygen group in the original COT study were associated with a stronger increase in the risk of death or disability than such episodes occurring infants randomized to the lower oxygen saturation target range. 

Dr. Audrey J Gaskins Department of Nutrition Harvard T.H. Chan School of Public Health Boston, MAMedicalResearch.com Interview with: Dr. Audrey J Gaskins Department of Nutrition Harvard T.H. Chan School of Public Health Boston, MA Medical Research: What is the background for this study? What are the main findings? Dr. Gaskins: Previous studies have linked shift work, long working hours, and physical factors to an increased risk of menstrual cycle disturbances, spontaneous abortion, preterm birth, and low birth weight; however the association with fecundity is inconsistent. Several papers have also reviewed the occupational exposures of health care workers and concluded that reproductive health issues are a concern. Therefore we sought to determine the extent to which work schedules and physical factors were associated with fecundity in a large cohort of nurses. Women who work in an industry that requires them to work from a height or even lift heavy objects requires them to undertake training which guides them though the effective stages on how to work safely at heights. Without the right training, this sort of work can become very dangerous. Our main findings were that that working >40 hours per week and moving or lifting a heavy load >15 times per day (including repositioning or transferring patients) were associated with reduced fecundity in our cohort of female nurses planning pregnancy. However, all other factors such as frequency of night work, duration of rotating and non-rotating night shifts, and time spent walking or standing at work were not significantly associated with fecundity in this cohort.

Carmen J. Williams, M.D., Ph.D. Principal Investigator National Institute of Environmental HealthMedicalResearch.com Interview with: Carmen J. Williams, M.D., Ph.D. Principal Investigator National Institute of Environmental Health Medical Research: What is the background for this study? Dr. Williams: G-protein coupled receptors are used by almost all cells to receive signals from the outside of the cell and transduce these signals into actions within the cell. There are hundreds of these receptors, but many of them link to a protein named Gq to transmit their signals to other cellular proteins. Gq is found in most cells, including eggs, and activating Gq protein is one way to artificially activate the egg to begin developing into an embryo, even though it is not the way sperm normally do this. In fact, if the egg is activated before the sperm arrives it prevents the sperm from binding and fusing with the egg, so fertilization cannot take place. As a result, we thought that a mechanism might be in place within eggs to prevent them from being activated prematurely by signals that could activate Gq by triggering G-protein coupled receptors. RGS2 was a good candidate for this function because it binds to Gq in a way that prevents Gq from transmitting signals to other cellular proteins.

Stephen A. Krawetz, Ph.D. Associate Director C.S. Mott Center for Human Growth and Development, Charlotte B. Failing Professor of Fetal Therapy and Diagnosis, Department of Obstetrics and Gynecology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201MedicalResearch.com Interview with: Stephen A. Krawetz, Ph.D. Associate Director C.S. Mott Center for Human Growth and Development, Charlotte B. Failing Professor of Fetal Therapy and Diagnosis, Department of Obstetrics and Gynecology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, 48201 Medical Research: What is the background for this study? What are the main findings? Dr. Krawetz: The current study developed over approximately the past 20 years of work in my laboratory.  In the mid 1990s, along with David Miller, we independently discovered that sperm contain RNA.  This was followed by our joint publication in The Lancet that began to describe the RNAs in normal fertile males along with our paper in Nature that showed that RNA was delivered to the oocyte at fertilization.  Following these studies we assessed the ability of RNAs to be used as markers of morphologically abnormal sperm (teratozoospermia).  My laboratory then had the opportunity to explore the complexity of the population of sperm RNAs using Next Generation Sequencing.   We recently began the translation of this work from the bench to bedside which takes us to the current paper in Science Translational Medicine that was a multi-institutional collaborative effort.  Members of the team include Dr. Meritxell Jodar, Edward Sendler, Robert Goodrich, from my laboratory, along with Dr. Clifford L. Librach, Dr. Sergey I. Moskovtsev, and Sonja Swanson - CReATe Fertility Center, University of Toronto; Dr. Russ Hauser -Harvard University and Dr. Michael P. Diamond, Georgia Regents University. Here we tackled the issue of idiopathic infertility, that is, unknown infertility, since the couple appears normal in all respects.  We specifically framed our study as the contribution of the male and female as a couple towards the birth of a healthy child focusing on male idiopathic infertility within the setting of a Reproductive Clinic.  Representative publications from my laboratory that outline this part of my research program appear below. 1)            Jodar, M., Sendler, E., Moskovtsev, S. Librach, C., Goodrich, R., Swanson, S., Hauser, R., Diamond, M. and Krawetz, S.A. (2015) Absence of sperm RNA elements correlates with idiopathic male infertility. Science Translational Medicine, 7(295):295re6. 2)            Sendler, E., Johnson, G.D., Mao, S., Goodrich, R.J., Diamond, M.P., Hauser, R., and Krawetz, S.A. (2013) Stability, Delivery and Functions of Human Sperm RNAs at Fertilization.  Nucleic Acids Research 41:4104-4117. PMID: 23471003 3)            Platts, A.E., Dix, D. J., Chemes, H.E., Thompson, K.E., Goodrich, R., Rockett, J. C., Rawe, V.Y., Quintana, S., Diamond, M.P., Strader, L.F. and Krawetz, S.A. (2007)  Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs.  Human Molecular Genetics. 16:763-773.  PMID: 17327269 4)            Ostermeier, G.C., Miller, D., Huntriss, J.D., Diamond, M.P. and Krawetz, S.A. (2004) Delivering spermatozoan RNA to the oocyte.  Nature 429:154.  PMID: 15141202 5)            Ostermeier, G.C., Dix, D.J., Miller, D., Khatri, P. and Krawetz, S.A. (2002) Spermatozoal RNA profiles of normal fertile men. The Lancet. 360:773-777.  PMID: 12241836