Fertility Research at CHR

Driving Force behind CHR’s Clinical Success

CHR is a rare private fertility center that combines clinical fertility care with a robust clinical and laboratory research program. In over 30 years since its inception, CHR researchers have published hundreds of research papers, many in prestigious medical journals like Journal of the American Medical Association (JAMA) and New England Journal of Medicine (NEJM). CHR’s medical journal publications are listed below.

Some of CHR’s original research findings brought revolutionary new approaches to the field of reproductive endocrinology and infertility. Involvement of autoimmunity in endometriosis is one; the now-routine transvaginal egg retrieval is another; and the most recent example is the introduction of DHEA supplementation into the treatment of women with diminished ovarian reserve.

CHR Explains

CHR’s focus has been the mechanism and treatment of diminished ovarian reserve for over a decade now, and many of our research publications are in this area. In the past few years, CHR has also expanded its laboratory research division significantly with 3 PhD-level scientists to conduct translational research in molecular biology and genetics. CHR’s Medical Director and Chief Scientist, Dr. Norbert Gleicher, emphasizes rigorous translational research because research is what drives innovation in fertility treatment at CHR, and our patients benefit directly from our research findings, which are “translated” into our clinical care program.

Infertility Clinical Trials

Clinical trials are considered the gold standard of research, and at any given time, CHR is likely to have more than one ongoing clinical trials. Some clinical trials recruit participants, while others may be open by invitation only.

CHR’s Medical Journal Publications

Improvements in IVF in women of advanced age.

IVF success rates for women over 40 can improve with pretreatment targeting the early stages of egg development.

Published in Journal of Endocrinology

Women above age 40 years in the US now represent the most rapidly growing age group having children. Patients undergoing in vitro fertilization (IVF) are rapidly aging in parallel. Especially where egg donations are legal, donation cycles, therefore, multiply more rapidly than autologous IVF cycles. The donor oocytes, however, are hardly ever a preferred patient choice. Since with use of own eggs, live birth rates decline with advancing age but remain stable (and higher) with donor eggs, older patients always face the difficult and very personal choice between poorer chances with own and better chances with donor oocytes. Physician contribution to this decision should in our opinion be restricted to accurate outcome information for both options. Achievable pregnancy and live birth rates in older women are, however, frequently underestimated, thereby mistakenly biasing fertility providers, private insurance companies and even regulatory government agencies. Restriction on access to IVF for older women is then often the consequence. In this review, we summarize the limited published data on best treatments of ‘older‘ ovaries, while also addressing treatment approaches that should be avoided in older women. This focused review, therefore, to a degree is subjective. Research addressing aging ovaries in IVF has been disappointingly sparse, and has in our opinion too heavily concentrated on methods of embryo selection (ES), which, especially in older women, not only fail to improve IVF outcomes, but actually, negatively affect live birth chances. We conclude that, aside from breakthroughs in gamete creation, only pharmacological interventions into early (small growing follicle stages) follicle maturation will offer new potential to positively impact oocyte and embryo quality and, therefore, IVF outcomes. Research, therefore, should be accordingly redirected.

Citation Page #: 230(1):F1-6
Journal: Journal of Endocrinology
Author Publication: Gleicher N, Kushnir VA, Albertini DF, Barad DH.
Link: View Publication
Date: 2016

Categories: Diminished Ovarian Reserve, Egg Quality, IVF, IVF Success Rates, Pregnacy After 40, Research

Definition by FSH, AMH and embryo numbers of good-, intermediate- and poor-prognosis patients suggests previously unknown IVF outcome-determining factor associated with AMH.

In IVF patients, mid-range anti-Müllerian hormone (AMH) levels were associated with the highest IVF pregnancy rates, while the lower and higher AMH levels predicted poorer outcomes.

Published in Journal of Translational Medicine

Background
Though outcome models have been proposed previously, it is unknown whether cutoffs in clinical pregnancy and live birth rates at all ages are able to classify in vitro fertilization (IVF) patients into good-, intermediate- and poor prognosis.

Methods
We here in 3 infertile patient cohorts, involving 1247, 1514 and 632 women, built logistic regression models based on 3 functional ovarian reserve (FOR) parameters, including (1) number of good quality embryos, (2) follicle stimulating hormone (FSH, mIU/mL) and (3) anti-Müllerian hormone (AMH, ng/mL), determining whether clinical pregnancy and live birth rates can discriminate between good, intermediate and poor prognosis patients.

Results
All models, indeed, allowed at all ages for separation by prognosis, though cut offs changed with age. In the embryo model, increasing embryo production resulted in linear improvement of IVF outcomes despite transfer of similar embryo numbers; in the FSH model outcomes and FSH levels related inversely, while the association of AMH followed a bell-shaped polynomial pattern, demonstrating “best” outcomes at mid-ranges. All 3 models demonstrated increasingly poor outcomes with advancing ages, though “best” AMH even above age 43 was still associated with unexpectedly good pregnancy and delivery outcomes. Excessively high AMH, in contrast, was at all ages associated with spiking miscarriage rates.

Conclusions
At varying peripheral serum concentrations, AMH, thus, demonstrates hitherto unknown and contradictory effects on IVF outcomes, deserving at different concentrations investigation as a potential therapeutic agent, with pregnancy-supporting and pregnancy-interrupting properties.

Citation Page #: 10;14(1):172
Journal: Journal of Translational Medicine
Author Publication: Gleicher N, Kushnir VA, Sen A, Darmon SK, Weghofer A, Wu YG, Wang Q, Zhang L, Albertini DF, Barad DH.
Link: View Publication
Date: 2016

Categories: Anti-Müllerian Hormone, Diminished Ovarian Reserve, Egg Quality, High FSH, IVF, IVF Success Rates, Research

How the FMR1 gene became relevant to female fertility and reproductive medicine

A comprehensive overview of the FMR1 gene’s effects on ovarian function and follicle maturation, and its potential role as an important diagnostic tool for functional ovarian reserve.

Citation Page #: 5;284.
Journal: Frontiers Genetics
Author Publication: Gleicher N, Kushnir VA, Weghofer A, Barad DH.
Link: View Publication
Date: 2014

Categories: Diminished Ovarian Reserve, FMR1

Effects of inter-cycle interval on oocyte production in humans in the presence of the weak androgen DHEA and follicle stimulating hormone: a case-control study

Repeat exposures to androgens like DHEA and FSH in short intervals improves functional ovarian reserve and increase pregnancy chances in humans, confirming the results of prior animal studies.

Citation Page #: 12:68.
Journal: Reprod Biol Endocrinol
Author Publication: Barad DH, Kushnir VA, Lee H-J, Lazzaroni-Tealdi E, Gleicher N.
Link: View Publication
Date: 2014

Categories: DHEA

Letter to the Editor: Poor responders and androgen adjuvant treatment: “Still haven’t found what I’m looking for …”

The paper offers a concise summary of rationale for androgen supplementation in women with LFOR to maximize pregnancy chances, in response to uninformed skepticism.

Citation Page #: 29(5):650-2.
Journal: Reprod Biomed Online
Author Publication: Gleicher N, Barad DH, Kushnir VA, Sen A, Weghofer A.
Link: View Publication
Date: 2014

Categories: DHEA, Ovarian Reserve

The "graying" of infertility services: an impending revolution nobody is ready for

Revolutionary change in infertility practice looms large with more older women seeking ART. Medical practice will have to adapt as women in their 50s and 60s start conceiving.

Citation Page #: 12:63.
Journal: Reprod Biol Endocrinol
Author Publication: Gleicher N, Kushnir VA, Weghofer A, Barad DH.
Link: View Publication
Date: 2014

Categories: Ovarian Reserve, Pregnacy After 40

Absence of BRCA/FMR1 correlations in women with ovarian cancers.

Study of BRCA1/2 mutation did not show correlation between low FMR1 alleles and BRCA-positive ovarian cancer patients.

Citation Page #: 9(7): e102370.
Journal: PLoS ONE
Author Publication: Gleicher N, McAlpine JN, Gilks CB, Kushnir VA, Lee H-J, Wu Y-G, Lazzaroni-Tealdi E, Barad DH.
Link: View Publication
Date: 2014

Categories: FMR1, Testing & Diagnostics

Ovarian reserve screening prior to contraception?

Hormonal contraceptives can deter detection of POF. The study proposes risk screenings before women begin taking contraceptives.

Citation Page #: In press.
Journal: Reprod Biomed Online
Author Publication: Kushnir VA, Barad DH, Gleicher N.
Link: View Publication
Date: 2014

Categories: Anti-Müllerian Hormone, Fertility Preservation, Premature Ovarian Failure, Testing & Diagnostics

Utilizing FMR1 gene mutations as predictors of treatment success in human in vitro fertilization.

In this study, low FMR1 alleles lowered IVF pregnancy rates by reducing egg and embryo quality.

Citation Page #: 9(7): e102274.
Journal: PLoS ONE
Author Publication: Kushnir VA, Yu Y, Barad DH, Weghofer A, Himaya E, Lee H-J, Wu Y-G, Shohat-Tal A, Lazzaroni-Tealdi E, Gleicher N.
Link: View Publication
Date: 2014

Categories: Egg Quality, FMR1, Ovarian Reserve, Testing & Diagnostics

Preimplantation genetic screening (PGS) still in search of a clinical application: a systematic review.

Newly updated “PGS#2” faces a multitude of issues, chief among them appropriate patient selection. With its efficacy still unproven, the technique should be offered only on an experimental basis.

Citation Page #: 12:22.
Journal: Reprod Biol Endocrinol
Author Publication: Gleicher N, Kushnir VA, Barad DH.
Link: View Publication
Date: 2014

Categories: PGD

PGD

Fertility treatments and multiple births in the United States.

Focus for multiple birth prevention should be on IUI, not IVF, given IUI’s much higher risk of high-order multiples and complications.

Citation Page #: 370:1069-1071.
Journal: NEJM
Author Publication: Gleicher N, Kushnir VA, Barad DH.
Link: View Publication
Date: 2014

Categories: IVF, IVF & Twins

Maternal autoimmunity and adverse pregnancy outcomes.

This study explores the poorly understood mechanisms of autoimmune diseases like preeclampsia negatively affecting pregnancy outcomes.

Citation Page #: 50:83-89.
Journal: Journal of Autoimmunity
Author Publication: Gleicher N.
Link: View Publication
Date: 2014

Categories: Autoimmune Disease

A randomized clinical trial of endometrial perfusion with granulocyte colony-stimulating factor in in vitro fertilization cycles: impact on endometrial thickness and clinical pregnancy rates

In normal, older IVF patients, G-CSF does not affect endometrial thickness, implantation rates, or clinical pregnancy rates.

Citation Page #: 101(3):710-715.
Journal: Fertility & Sterility
Author Publication: Barad DH, Yu Y, Kushnir VA, Shohat-Tal A, Lazzaroni E, Lee HJ, Gleicher N.
Link: View Publication
Date: 2014

Categories: Failed IVF, IVF, Pregnacy After 40

What misguided campaign against SET?

CHR physicians argue against the supposed efficacy of single embryo transfer, based on cost-benefit analysis and statistical comparison of risks between twins and singletons.

Citation Page #: In press.
Journal: Human Reproduction
Author Publication: Gleicher N, Kushnir VA, Barad DH.
Date: 2014

Categories: IVF Success Rates

Preimplantation genetic screening is alive and very well: Really?

Though preimplantation genetic screening (PGS) was proven ineffective and costly for patients in a previous iteration, it is still marketed aggressively.

Citation Page #: e36.
Journal: Fertility & Sterility
Author Publication: Gleicher N, Kushnir VA, Barad DH.
Link: View Publication
Date: 2013

Categories: PGD

PGD

Do BRCA1/2 mutations and low FMR1 alleles interact or not?

Current evidence does not support the possibility of interplay between the BRCA mutation and the FMR1 gene; further exploration of this connection is necessary.

Citation Page #: Epub ahead of print

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