Center for Human Reproduction

Ribeirão Preto, Brazil

Center for Human Reproduction

Ribeirão Preto, Brazil
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News Article | January 5, 2016

Children conceived by means of fertility treatments do not appear to face any special risk of delays in their early development, a study suggests. Children born as a result of assisted reproductive technology develop during early childhood, up to the age of 3, at the same rate as other children, researchers say. The study should ease long-standing concerns that children conceived through in vitro fertilization or other fertility treatments might face developmental problems. Developmental assessment scores of more than 1,800 children born to women who became pregnant after receiving infertility treatments and those of more than 4,000 children born to women not undergoing such treatment showed no differences, the study appearing in the journal JAMA reported. "When we began our study, there was little research on the potential effects of conception via fertility treatments on U.S. children," says researcher Edwina Yeung at the National Institutes of Health's Eunice Kennedy Shriver National Institute of Child Health and Human Development. "Our results provide reassurance to the thousands of couples who have relied on these treatments to establish their families." While it is becoming more common for some women to undergo infertility treatments of one sort or another, just 1 to 2 percent of U.S. births are conceived with assisted reproductive technology, Yeung points out. Those ART technologies in the study included in vitro fertilization, when fertilization takes place in a lab dish after eggs and sperm are taken from the couple; frozen embryo transfer; assisted hatching, the placement of a microscopic hole in the protein covering of the embryo; gamete intrafallopian transfer, when sperm and egg are mixed before they are placed in the fallopian tube; zygote intrafallopian transfer, when a fertilized egg (zygote) is placed into the fallopian tube; ovulation induction; and intrauterine insemination, when sperm is placed directly in the uterus via a narrow tube. Concerns about possible effects of infertility treatments on child development are common among parents consider such options, experts in the field say. "I hear these questions all the time," says Dr. Norbert Gleicher at the Center for Human Reproduction in New York City. The issue is complicated by other factors that make it difficult for researchers to study, he notes. "Patients with infertility are often older, and may have medical conditions," he says. "You have to be able to differentiate those potential effects from any effects of the fertility treatment, per se." While some developmental issues such as autism usually don't manifest themselves as early as age 3, Yeung and her study co-authors say they will follow the study group of children through age 8. In the meantime, Yeung says, the study's findings should be welcome news for many couples considered treatment options. "This is a feel-good message of really just reassuring couples who are considering infertility treatment," she says.

Prizant H.,University of Rochester | Gleicher N.,Center for Human Reproduction | Sen A.,University of Rochester | Sen A.,Center for Human Reproduction
Journal of Endocrinology | Year: 2014

For many decades, elevated androgens in women have been associated with poor reproductive health. However, recent studies have shown that androgens play a crucial role in women's fertility. The following review provides an overall perspective about how androgens and androgen receptor-mediated actions regulate normal follicular development, as well as discuss emerging concepts, latest perceptions, and controversies regarding androgen actions and signaling in the ovary. © 2014 Society for Endocrinology.

Gleicher N.,Center for Human Reproduction | Gleicher N.,Foundation Medicine
Reproductive BioMedicine Online | Year: 2013

It has been known for decades that nulliparity is associated with an increased risk for certain reproductive malignancies, including breast, ovarian and uterine cancers. A recent commentary in The Lancet summarized the available evidence based on data in nulliparous women and concluded that the risk of nulliparity was related to the increased number of ovulatory cycles, and so might be preventable by utilization of oral contraceptives. That communication described significant differences in age-dependent cancer mortality in nulliparous nuns, as well as in parous controls, between breast, ovarian and uterine cancers. Moreover, the steep inclines in cancer mortality in nuns are only observed decades after the menopause. Taken together, these observations make it appear unlikely that the number of ovulations is associated aetiologically with increased cancer risks in nulliparous nuns. Here are postulated other possible primary mechanisms that could be responsible for the reported age-related increase in cancer risks in nulliparous women, such as nuns, and conclude that a better understanding of such mechanisms may offer important new insights into tumour initiation in general. © 2013, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Gleicher N.,Center for Human Reproduction | Gleicher N.,Foundation Medicine | Elkayam U.,University of Southern California
Autoimmunity Reviews | Year: 2013

Offspring of women with anti-SSA/Ro-SSB/La antibodies are believed to be at risk for congenital heart block (CHB). Whether this risk can be reduced, and what constitutes standard of care treatment is, however, unclear. The objective of this review therefore was to determine whether currently proposed standard of care treatments to avoid CHB in offspring of mothers at risk are evidence-based. To do so, we conducted a review of the literature under appropriate keywords and phrases in Medline/PubMed and Google Scholar for the years 2000-2013. Reference lists were further reviewed, and relevant manuscripts were pulled. We also reviewed for registered studies. In the absence of randomized prospective clinical trials, a meta-analysis was not feasible. We, therefore, reviewed lower evidence level studies individually. Risk of CHB actually appears more closely associated with general autoimmunity than, specifically, with SSA/Ro-SSB/La antibodies. This and other observations raise questions whether CHB is caused by passively transferred maternal autoimmunity, as is currently widely believed. Observational studies suggest the possible effectiveness of intravenous gamma globulin (IV-Ig) and hydroxychloroquine (Plaquenil) in reducing CHB-risk. Evidence for both is, however, inconclusive, and studies are biased in favor of hydroxychloroquine and against IV-Ig. Based on the review of the literature, current evidence of effectiveness for any treatment has to be judged as insufficient. Among the available treatment options, some considerations favor IV-Ig over hydroxychloroquine or, alternatively, suggest treatment with IV-Ig periconceptionally and into early gestation, with hydroxychloroquine added or replacing IV-Ig at approximately 10. weeks gestational age. Benefits for the utilization of steroid drugs are unclear. Since no treatment can be considered as established, prevention of CHB in offspring should be considered experimental, and performed under appropriate study conditions. © 2013 Elsevier B.V.

After appropriate counseling and absent medical contraindications, if a patient desires twins, they should be welcomed. What is surprising to this author is the uncritical acceptance by so many colleagues of the notion that twins are "bad." How far some colleagues are willing to take this concept is best demonstrated by a recent paper from the same Finnish group that initially introduced eSET to the world.21 In this paper the authors, who themselves initially proposed eSET only for favorable patients, now propose eSET for women up to age 44. Can one responsibly suggest to a patient to have an eSET at age 44 because she always can have another child 12 to 18 months later? I don't think so.

Kushnir V.A.,Center for Human Reproduction | Vidali A.,New York Reproductive Services | Barad D.H.,Center for Human Reproduction | Barad D.H.,Foundation Medicine | And 2 more authors.
Fertility and Sterility | Year: 2013

Objective: To assess the transparency of assisted reproductive technology (ART) surveillance reports published by the Centers for Disease Control and Prevention (CDC) and by the Society for Assisted Reproductive Technologies (SART). Design: Retrospective analysis. Setting: Private clinical ART and research center. Patient(s): We analyzed ART data for the years 2005-2010, which were reported under federal mandate to the CDC (818,927 completed cycles) and voluntarily to SART (812,400 initiated cycles). Intervention(s): None. Main Outcome Measure(s): Initiated cycles excluded from final outcome reporting were used to evaluate transparency. Result(s): Only SART, but not CDC, reported initiated cycles, allowing analysis of excluded cycles. Excluded cycles increased significantly from 3.3% to 7.4% between 2005 and 2010. By 2010, 13/341 (3.8%) ART centers accounted for 50% of excluded cycles, representing an average of 37.3% of their cycles. These 13 clinics reported significantly better pregnancy and cancellations rates than national averages and collectively increased by 19.9% their share of U.S. ART cycles. Conclusion(s): Our data indicate decreasing transparency in public ART reporting in the United States, likely due to changes in practice and reporting patterns. A few clinics accounted for the majority of excluded cycles, leading to improved reported clinical outcomes and increasing market share. CDC and SART should ensure that all ART clinics publicly report the outcomes of all initiated cycles including embryo-banking cycles. ART surveillance and quality of care may be improved by prospectively tracking the total reproductive potential of each initiated cycle. © 2013 by American Society for Reproductive Medicine.

Gleicher N.,Center for Human Reproduction | Gleicher N.,Foundation Medicine | Gleicher N.,Yale University
Reproductive BioMedicine Online | Year: 2011

The manuscript in this issue of the journal by Bissonette et al. reports on a new government-sponsored intervention into the practice of IVF within the province of Quebec, Canada, which in the authors' opinion highly successfully reduced twinning rates, while maintaining overall acceptable pregnancy rates. Given the opportunity to comment, their manuscript, in my opinion, only reemphasizes why, despite wide professional support, the concept of single embryo transfer (SET) is: (i) damaging to most infertility patients by reducing pregnancy chances; (ii) does so without compensatory benefits; (iii) impinges on patients' rights to self-determination; (iv) has significant negative impact on IVF-generated birth rates; and (v) thus, demonstrating, once more, that governments should not interfere with the patient-physician relationships. © 2011, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

News Article | December 9, 2016

It's generally thought that women are born with a finite number of egg cells, and cannot grow new ones. But in a new study, researchers got a surprise when they found that women undergoing a particular chemotherapy had a much greater number of eggs in their ovaries than expected. The reason for the finding isn't clear, but it suggests that the chemotherapy may spur the development of new eggs, the researchers say. If confirmed, it would be the first time that scientists have seen new egg cells formed in adult women. And understanding exactly how this happens could aid in the development of fertility treatments that allow women to produce more eggs, the researchers said. However, the researchers caution that the study was small, and the findings do not prove that the chemotherapy treatment caused the production of new eggs. In addition, it's not clear whether the greater number of eggs seen in these women after the chemotherapy treatment would help with their fertility. In fact, another part of the study found that the eggs from these women didn't grow as well in a lab dish, compared to eggs from healthy women. [Conception Misconceptions: 7 Fertility Myths Debunked] "This study involves only a few patients, but its findings were consistent and its outcome may be significant and far-reaching," study researcher Evelyn Telfer, a professor at the University of Edinburgh's School of Biological Sciences, said in a statement. "We need to know more about how this drug combination acts on the ovaries, and the implications of this." Women are born with all of the eggs they will use in their lifetimes, but the eggs need to mature inside structures called follicles. Typically, one follicle matures each month, and releases an egg. As women age, the number of follicles in their ovaries declines, which reduces their chances of pregnancy. Some cancer treatments accelerate the loss of follicles, and thus hurt a women's fertility. But other cancer treatments don't seem to have an effect on fertility. In the new study, the researchers originally set out to examine why a common chemotherapy treatment for Hodgkin’s lymphoma (a cancer of white blood cells) doesn't appear to affect fertility. The treatment is a combination of four chemotherapy drugs — adriamycin, bleomycin, vinblastine and dacarbazine — or ABVD for short. The researchers analyzed samples of ovarian tissue donated by 8 women who had undergone ABVD, 3 women who had undergone a different type of chemotherapy and 12 healthy women around the same age. Women who received the ABVD treatment had a much greater number of immature follicles in their ovaries —up to 10 times higher in some cases — than healthy women and those who'd received the other chemotherapy, the study found. Women who'd received ABVD also had a much greater number of follicles than would be expected based on their age. The follicles in ABVD group also appeared younger — similar to those seen in girls before they go through puberty. When the researchers tried to grow the follicle in a lab dish, those from the ABVD group didn't grow as well as those from the other two groups - only about 20 percent of follicles from the ABVD group showed growth, compared to 42 to 46 percent in the other two groups, the study found. This limited follicle development is also comparable to what's seen in prepubescent girls, the researchers said. The researchers speculate that the ABVD treatment may active stem cells within the ovary to produce new eggs. "It could be that the harshness of the treatment triggers some kind of shock effect or perturbation which stimulates the stem cells into producing new eggs," Telfer told the Telegraph. But there could be other explanations, including that the egg follicles were damaged during treatment and split into two or more parts, David Albertini, laboratory director at the Center for Human Reproduction in New York, told the Guardian. Future studies will examine the effect of each of the four chemotherapy drugs separately, to better understand the mechanism that may be leading to an increased number of follicles, the researchers said. The study was published online Dec. 5 in the journal Human Reproduction.

Hershlag A.,Center for Human Reproduction
Journal of pediatric and adolescent gynecology | Year: 2011

Teenage girls who have survived childhood and adolescent cancer are at risk of losing ovarian function as a result of treatment. This iatrogenic complication may compromise their ability to conceive in the future. In addition, the more immediate consequence is interference in the physical, sexual, and psychosocial development of the female adolescent and her ability to "graduate" into young adulthood. This paper lends strong support to meticulous, graduated hormone replacement, mimicking Tanner's stages of pubertal development, to allow smooth transition of adolescent cancer survivors into adulthood.

Sen A.,Center for Human Reproduction | Kushnir V.A.,Center for Human Reproduction | Barad D.H.,Center for Human Reproduction | Gleicher N.,Center for Human Reproduction
Nature Reviews Endocrinology | Year: 2014

An increasing body of evidence suggests that immune-mediated processes affect female reproductive success at multiple levels. Crosstalk between endocrine and immune systems regulates a large number of biological processes that affect target tissues, and this crosstalk involves gene expression, cytokine and/or lymphokine release and hormone action. In addition, endocrine-immune interactions have a major role in the implantation process of the fetal (paternally derived) semi-allograft, which requires a reprogramming process of the maternal immune system from rejection to temporary tolerance for the length of gestation. Usually, the female immune system is supportive of all of these processes and, therefore, facilitates reproductive success. Abnormalities of the female immune system, including autoimmunity, potentially interfere at multiple levels. The relevance of the immune system to female infertility is increasingly recognized by investigators, but clinically is often not adequately considered and is, therefore, underestimated. This Review summarizes the effect of individual autoimmune endocrine diseases on female fertility, and points towards selected developments expected in the near future. © 2014 Macmillan Publishers Limited. All rights reserved.

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