Publications by authors named "Sherman J Silber"

36 Publications

Generation of three human induced pluripotent stem cell sublines (UCLAi004-A, UCLAi004-B, and UCLAi004-C) for reproductive science research.

Stem Cell Res 2021 Jul 24;54:102446. Epub 2021 Jun 24.

Department of Molecular, Cell and Developmental Biology, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, CA, USA. Electronic address:

Three induced pluripotent stem cell sublines (hiPSCs) were generated from human dermal human dermal fibroblasts (HDFs) derived from a human skin punch biopsy. The biopsy was donated from a woman with known infertility due to ovarian failure. The hiPSC sublines were created using Sendai virus vectors and were positive for markers of self-renewal including OCT4, NANOG, TRA-1-81 and SSEA-4. Pluripotency was verified using PluriTest analysis and in vitro differentiation using Taqman Real-Time PCR assays for somatic lineage markers. This participant's monozygotic twin sister also donated a skin-punch biopsy, whose resulting hiPSC lines were published previously as a resource.
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http://dx.doi.org/10.1016/j.scr.2021.102446DOI Listing
July 2021

Generation of three human induced pluripotent stem cell sublines (UCLAi005-A, UCLAi005-B and UCLAi005-C) for reproductive science research.

Stem Cell Res 2021 Jul 8;54:102409. Epub 2021 Jun 8.

Department of Molecular, Cell and Developmental Biology, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA USA; Molecular Biology Institute, University of California, Los Angeles, CA, USA. Electronic address:

We generated three human induced pluripotent stem cell (hiPSC) sublines from human dermal fibroblasts (HDF) (MZT05) generated from a skin biopsy donated from a previously fertile woman. The skin biopsy was broadly consented for generating hiPSC lines for biomedical research, including unique consent specifically for studying human fertility, infertility and germ cell differentiation. hiPSCs were reprogrammed using Sendai virus vectors and were subsequently positive for markers of self-renewal. Pluripotency was further verified using PluriTest analysis and in vitro differentiation was tested using Taqman Real-Time PCR assays. These sublines serve as controls for hiPSC research projects aimed at understanding the cell and molecular regulation of female fertility.
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http://dx.doi.org/10.1016/j.scr.2021.102409DOI Listing
July 2021

Generation of six human induced pluripotent stem cell sublines (MZT01E, MZT01F, MZT01N and MZT02D, MZT02G and MZT02H) for reproductive science research.

Stem Cell Res 2021 03 27;51:102204. Epub 2021 Jan 27.

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, CA, USA.

Six human induced pluripotent stem cell sublines (hiPSCs) were generated from human dermal fibroblasts (HDFs) derived from skin biopsies donated from monozygotic twin women wherein one woman had proven fertility and her sister was infertile due to ovarian failure. Three hiPSC sublines were created from each twin's HDFs. hiPSCs were reprogrammed using Sendai virus vectors and were subsequently positive for markers of self-renewal including OCT4, NANOG, TRA-1-81 and SSEA-4. Pluripotency was further verified using PluriTest. We show here that the hiPSC lines created from the twins are equivalent in measures of pluripotency and self-renewal, despite their differential diagnosis.
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http://dx.doi.org/10.1016/j.scr.2021.102204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043044PMC
March 2021

When "facts" are not facts: what does p value really mean, and how does it deceive us?

J Assist Reprod Genet 2020 Jun 7;37(6):1303-1310. Epub 2020 Apr 7.

Infertility Center of St. Louis, St. Louis, MO, USA.

The recent paper in JAMA alleging that frozen embryo transfer causes twice the risk of childhood cancer in the offspring is an excellent example of the erroneous use of statistical tests (and the misinterpretation of p value) that is common in much of the medical literature, even in very high impact journals. These myths backed by misleading statements of "statistical significance" can cause far-reaching harm to patients and doctors who might not understand the pitfalls of specious statistical testing.
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http://dx.doi.org/10.1007/s10815-020-01751-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311604PMC
June 2020

Generation of three human induced pluripotent stem cell sublines (MZT04D, MZT04J, MZT04C) for reproductive science research.

Stem Cell Res 2019 10 16;40:101576. Epub 2019 Sep 16.

Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles, CA, USA. Electronic address:

We generated three human induced pluripotent stem cell (hiPSC) sublines from human dermal fibroblasts (HDFs) (MZT04) generated from a skin biopsy donated from a previously fertile woman. The skin biopsy was broadly consented for generating hiPSC lines for biomedical research, including unique consent specifically for studying human fertility, infertility and germ cells. hiPSCs were reprogrammed using Sendai virus vectors and were subsequently positive for markers of self-renewal including OCT4, NANOG, TRA-1-81 and SSEA-4. Pluripotency was further verified using teratomas and PluriTest. These sublines serve as controls for hiPSC research projects aimed at understanding the cell and molecular regulation of female fertility and infertility.
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http://dx.doi.org/10.1016/j.scr.2019.101576DOI Listing
October 2019

Cryopreservation and transplantation of ovarian tissue: results from one center in the USA.

J Assist Reprod Genet 2018 Dec 25;35(12):2205-2213. Epub 2018 Sep 25.

St. Luke's Hospital Pathology, 232 South Woods Mill Road, St. Louis, MO, 63017, USA.

Purpose: To report the results of cryopreserved ovary tissue transplantation for leukemia and other cancers, in a single US center.

Methods: One hundred eight females between age 6 and (median age 24) 35 were referred for possible ovary tissue cryopreservation over a 20-year period, with either slow freeze or vitrification. Thus far 13 patients returned up to 18 years later to have their tissue transplanted back.

Results: All 13 patients had return of ovarian function 5 months post transplant with regular menstrual cycling. AMH rose to very high levels as the FSH declined to normal. Four months later, the AMH again declined to very low levels. Nonetheless, the grafts remained functional for up to 5 years or longer. Ten of the 13 (77%) became spontaneously pregnant at least once, resulting in 13 healthy babies. A total of 24 healthy babies have been born 11 from fresh transplanted ovarian tissue and 13 from cryopreserved transplanted ovarian tissue.

Conclusions: (1) Ovary tissue cryopreservation is a robust method for preserving a woman's fertility. (2) Cortical tissue pressure may be a key regulator of primordial follicle arrest, recruitment, and ovarian longevity. (3) This is the only such series yet reported in the USA.
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http://dx.doi.org/10.1007/s10815-018-1315-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289920PMC
December 2018

Corrigendum to 'Live birth derived from oocyte spindle transfer to prevent mitochondrial disease': [Reproductive BioMedicine Online 34 (2017) 361-368].

Reprod Biomed Online 2017 12 20;35(6):750. Epub 2017 Jul 20.

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. Electronic address:

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http://dx.doi.org/10.1016/j.rbmo.2017.07.008DOI Listing
December 2017

Unraveling transcriptome dynamics in human spermatogenesis.

Development 2017 10 21;144(20):3659-3673. Epub 2017 Sep 21.

Center for Reproductive Medicine, Amsterdam Research Institute Reproduction and Development, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

Spermatogenesis is a dynamic developmental process that includes stem cell proliferation and differentiation, meiotic cell divisions and extreme chromatin condensation. Although studied in mice, the molecular control of human spermatogenesis is largely unknown. Here, we developed a protocol that enables next-generation sequencing of RNA obtained from pools of 500 individually laser-capture microdissected cells of specific germ cell subtypes from fixed human testis samples. Transcriptomic analyses of these successive germ cell subtypes reveals dynamic transcription of over 4000 genes during human spermatogenesis. At the same time, many of the genes encoding for well-established meiotic and post-meiotic proteins are already present in the pre-meiotic phase. Furthermore, we found significant cell type-specific expression of post-transcriptional regulators, including expression of 110 RNA-binding proteins and 137 long non-coding RNAs, most of them previously not linked to spermatogenesis. Together, these data suggest that the transcriptome of precursor cells already contains the genes necessary for cellular differentiation and that timely translation controlled by post-transcriptional regulators is crucial for normal development. These established transcriptomes provide a reference catalog for further detailed studies on human spermatogenesis and spermatogenic failure.
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http://dx.doi.org/10.1242/dev.152413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5675447PMC
October 2017

Corrigendum to 'Live birth derived from oocyte spindle transfer to prevent mitochondrial disease' [Reproductive BioMedicine Online 34 (2017) 361-368].

Reprod Biomed Online 2017 07 8;35(1):49. Epub 2017 May 8.

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. Electronic address:

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http://dx.doi.org/10.1016/j.rbmo.2017.04.002DOI Listing
July 2017

Intrinsic fertility of human oocytes.

Fertil Steril 2017 05 19;107(5):1232-1237. Epub 2017 Apr 19.

Kato Ladies Clinic, Tokyo, Japan.

Objective: To study the intrinsic fertility of the human oocyte.

Design: A large retrospective study of natural cycle single embryo transfer (ET) IVF cycles.

Setting: Private IVF clinic, university, and private hospital.

Patient(s): Patients were enrolled consecutively over an 8-year period in a single ET natural cycle protocol.

Intervention(s): A total of 13,949 oocyte retrievals with natural IVF single ET. Software package R (version 3.2.5) was used for statistical calculations.

Main Outcome Measure(s): Live baby rate per oocyte according to age.

Result(s): A total of 14,185 natural cycle oocytes resulted in 1,913 live babies from single ET. The number of oocytes required to make one live baby in this large series varied with the age of the female partner. For those under 35, the live baby born per oocyte was 26%. For over age 42 it decreased to 1%. These results fit very robustly with a logistic function curve, which is at first steady (horizontal), followed by a linear decline after age 35 with a 10% loss every year until age 43, and then a flattening out (horizontal) by age 44.

Conclusion(s): The intrinsic fertility per oocyte in natural cycle is far greater than reported in hyperstimulated cycles, varying robustly from 26% to 4% with age from <35 to 42 years. The curve is relatively flat until age 34, and then declines rapidly 10% per year thereafter.
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http://dx.doi.org/10.1016/j.fertnstert.2017.03.014DOI Listing
May 2017

Live birth derived from oocyte spindle transfer to prevent mitochondrial disease.

Reprod Biomed Online 2017 04;34(4):361-368

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. Electronic address:

Mutations in mitochondrial DNA (mtDNA) are maternally inherited and can cause fatal or debilitating mitochondrial disorders. The severity of clinical symptoms is often associated with the level of mtDNA mutation load or degree of heteroplasmy. Current clinical options to prevent transmission of mtDNA mutations to offspring are limited. Experimental spindle transfer in metaphase II oocytes, also called mitochondrial replacement therapy, is a novel technology for preventing mtDNA transmission from oocytes to pre-implantation embryos. Here, we report a female carrier of Leigh syndrome (mtDNA mutation 8993T > G), with a long history of multiple undiagnosed pregnancy losses and deaths of offspring as a result of this disease, who underwent IVF after reconstitution of her oocytes by spindle transfer into the cytoplasm of enucleated donor oocytes. A male euploid blastocyst wasobtained from the reconstituted oocytes, which had only a 5.7% mtDNA mutation load. Transfer of the embryo resulted in a pregnancy with delivery of a boy with neonatal mtDNA mutation load of 2.36-9.23% in his tested tissues. The boy is currently healthy at 7 months of age, although long-term follow-up of the child's longitudinal development remains crucial.
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http://dx.doi.org/10.1016/j.rbmo.2017.01.013DOI Listing
April 2017

Clean, Intermittent Self-Catheterization in the Treatment of Urinary Tract Disease.

J Urol 2017 02 21;197(2S):S122-S124. Epub 2016 Dec 21.

Section of Urology, Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan.

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http://dx.doi.org/10.1016/j.juro.2016.10.097DOI Listing
February 2017

Parallel evolution of male germline epigenetic poising and somatic development in animals.

Nat Genet 2016 08 13;48(8):888-94. Epub 2016 Jun 13.

Whitehead Institute, Cambridge, Massachusetts, USA.

Changes in gene regulation frequently underlie changes in morphology during evolution, and differences in chromatin state have been linked with changes in anatomical structure and gene expression across evolutionary time. Here we assess the relationship between evolution of chromatin state in germ cells and evolution of gene regulatory programs governing somatic development. We examined the poised (H3K4me3/H3K27me3 bivalent) epigenetic state in male germ cells from five mammalian and one avian species. We find that core genes poised in germ cells from multiple amniote species are ancient regulators of morphogenesis that sit at the top of transcriptional hierarchies controlling somatic tissue development, whereas genes that gain poising in germ cells from individual species act downstream of core poised genes during development in a species-specific fashion. We propose that critical regulators of animal development gained an epigenetically privileged state in germ cells, manifested in amniotes by H3K4me3/H3K27me3 poising, early in metazoan evolution.
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http://dx.doi.org/10.1038/ng.3591DOI Listing
August 2016

Live birth rates after MESA or TESE in men with obstructive azoospermia: is there a difference?

Hum Reprod 2015 Apr 3;30(4):761-6. Epub 2015 Mar 3.

Center for Reproductive Medicine, Women's and Children's Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Infertility Center of St. Louis, St. Luke's Hospital, St. Louis, MO 63017, USA

Study Question: How do live birth rates compare after intracytoplasmic sperm injection (ICSI) for men with obstructive azoospermia when using sperm derived from testicular sperm extraction (TESE) versus microsurgical epididymal sperm aspiration (MESA)?

Summary Answer: Our study suggests that proximal epididymal sperm (from MESA) result in higher live birth rates as compared with testicular sperm (from TESE) in couples where the man has obstructive azoospermia due to congenital bilateral absence of the vas deferens (CBAVD) or vasectomy.

What Is Known Already: For couples with obstructive azoospermia, MESA (epididymal sperm) and TESE (testicular sperm) have generally been assumed to be equivalent for use in ICSI. But this assumption has never been confirmed, and this view has important clinical and basic scientific consequences.

Study Design, Size, Duration: This was a retrospective study of a consecutive cohort of 374 men with obstructive azoospermia and normal spermatogenesis, who underwent IVF and ICSI using either epididymal sperm or testicular sperm in the period 2000-2009.

Participants/materials, Setting, Methods: The study included men undergoing MESA or TESE at St. Luke's Hospital for obstructive azoospermia due to CBAVD or vasectomy.

Main Results And The Role Of Chance: A total of 280 couples underwent MESA and 94 underwent TESE with ICSI. The live birth rate was 39% after MESA-ICSI and 24% after TESE-ICSI. The MESA-ICSI cycles also resulted in a significantly higher implantation rate and significantly higher clinical and ongoing pregnancy rates than the TESE-ICSI cycles. There was no significant difference in results between fresh or frozen sperm for both MESA and TESE. When adjusted for the available confounders, the odds ratio for live birth was significantly in favour of MESA-ICSI versus TESE-ICSI (OR 1.82; 95% CI 1.05-3.67). The only significant confounders were female age and ovarian reserve.

Limitations, Reasons For Caution: This is a retrospective cohort study and not a randomized clinical trial.

Wider Implications Of The Findings: Our study suggests that some aspect of sperm maturation after the sperm leaves the testicle to enter the epididymis is required for the most optimal results, even when ICSI is used for fertilization.

Study Funding/competing Interests: No funding was used and there are no competing interests.
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http://dx.doi.org/10.1093/humrep/dev032DOI Listing
April 2015

Applying clinically proven human techniques for contraception and fertility to endangered species and zoo animals: a review.

J Zoo Wildl Med 2013 Dec;44(4 Suppl):S111-22

Infertility Center of St. Louis, St. Luke's Hospital, Missouri 63017, USA.

Reversible contraception that does not alter natural behavior is a critical need for managing zoo populations. In addition to reversible contraception, other fertility techniques perfected in humans may be useful, such as in vitro fertilization (IVF) or oocyte and embryo banking for endangered species like amphibians and Mexican wolves (Canis lupus baileyi). Furthermore, the genetics of human fertility can give a better understanding of fertility in more exotic species. Collaborations were established to apply human fertility techniques to the captive population. Reversible vasectomy might be one solution for reversible contraception that does not alter behavior. Reversible approaches to vasectomy, avoiding secondary epididymal disruption, were attempted in South American bush dogs (Speothos venaticus), chimpanzees (Pan troglodytes), gorillas (Gorilla gorilla), Przewalski's horse (Equus przewalski poliakov), and Sika deer (Cervus nippon) in a variety of zoos around the world. These techniques were first perfected in > 4,000 humans before attempting them in zoo animals. In vitro fertilization with gestational surrogacy was used to attempt to break the vicious cycle of hand rearing of purebred orangutans, and egg and ovary vitrification in humans have led to successful gamete banking for Mexican wolves and disappearing amphibians. The study of the human Y chromosome has even explained a mechanism of extinction related to global climate change. The best results with vasectomy reversal (normal sperm counts, pregnancy, and live offspring) were obtained when the original vasectomy was performed "open-ended," so as to avoid pressure-induced epididymal disruption. The attempt at gestational surrogacy for orangutans failed because of severe male infertility and the lack of success with human ovarian hyperstimulation protocols. Vitrification of oocytes is already being employed for the Amphibian Ark Project and for Mexican wolves. Vasectomy can be a reversible contraception option in zoo animals, even in endangered species. Ongoing use of gamete and embryo freezing may salvage vanishing species.
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http://dx.doi.org/10.1638/1042-7260-44.4S.S111DOI Listing
December 2013

AZFc deletions and spermatogenic failure: a population-based survey of 20,000 Y chromosomes.

Am J Hum Genet 2012 Nov 25;91(5):890-6. Epub 2012 Oct 25.

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

Deletions involving the Y chromosome's AZFc region are the most common known genetic cause of severe spermatogenic failure (SSF). Six recurrent interstitial deletions affecting the region have been reported, but their population genetics are largely unexplored. We assessed the deletions' prevalence in 20,884 men in five populations and found four of the six deletions (presented here in descending order of prevalence): gr/gr, b2/b3, b1/b3, and b2/b4. One of every 27 men carried one of these four deletions. The 1.6 Mb gr/gr deletion, found in one of every 41 men, almost doubles the risk of SSF and accounts for ∼2% of SSF, although <2% of men with the deletion are affected. The 1.8 Mb b2/b3 deletion, found in one of every 90 men, does not appear to be a risk factor for SSF. The 1.6 Mb b1/b3 deletion, found in one of every 994 men, appears to increase the risk of SSF by a factor of 2.5, although <2% of men with the deletion are affected, and it accounts for only 0.15% of SSF. The 3.5 Mb b2/b4 deletion, found in one of every 2,320 men, increases the risk of SSF 145 times and accounts for ∼6% of SSF; the observed prevalence should approximate the rate at which the deletion arises anew in each generation. We conclude that a single rare variant of major effect (the b2/b4 deletion) and a single common variant of modest effect (the gr/gr deletion) are largely responsible for the AZFc region's contribution to SSF in the population.
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http://dx.doi.org/10.1016/j.ajhg.2012.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3487143PMC
November 2012

Long-term duration of function of ovarian tissue transplants: case reports.

Reprod Biomed Online 2012 Aug 5;25(2):128-32. Epub 2012 Apr 5.

Laboratory of Reproductive Biology, The Juliane Marie Centre for Women, Children and Reproduction, University Hospital of Copenhagen, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark.

These three case reports describe the long-term duration of function of ovarian cortical tissue grafts among patients in a university fertility preservation programme in Europe and in a private practice programme in the USA. One woman underwent sterilizing cancer treatment and had frozen ovarian tissue transplanted, and two women underwent fresh ovarian tissue transplants. The function of ovarian cortical strips has continued for more than 7 years in these three women, with the birth of eight healthy babies following a single graft per patient. In addition to these three cases, transplantation (repeatedly in some cases) of cryopreserved ovarian tissue has restored reproductive function to all other women in the study centres' programmes for some years. The sustained longevity of function of the transplanted tissue suggests that it may also be possible to postpone the normal time of menopause or to alleviate its symptoms.
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http://dx.doi.org/10.1016/j.rbmo.2012.03.014DOI Listing
August 2012

The Y chromosome in the era of intracytoplasmic sperm injection: a personal review.

Authors:
Sherman J Silber

Fertil Steril 2011 Jun;95(8):2439-48.e1-5

Infertility Center of St. Louis, St. Luke's Hospital, St. Louis, Missouri 63017, USA.

The Y chromosome contains 60 multicopy genes composed of nine different gene families concentrated in regions of multiple repeat sequences called amplicons arranged in mirror images called palindromes. This pattern is susceptible to deletions caused by homologous recombination with itself, and can explain the presence of small numbers of sperm in otherwise azoospermic men.
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http://dx.doi.org/10.1016/j.fertnstert.2011.05.070DOI Listing
June 2011

Sperm retrieval for azoospermia and intracytoplasmic sperm injection success rates--a personal overview.

Authors:
Sherman J Silber

Hum Fertil (Camb) 2010 Dec;13(4):247-56

Infertility Center of St Louis, St Luke's Hospital, St Louis, USA.

It is often questioned whether sperm parameters, including whether retrieved or ejaculated, have any effect on intracytoplasmic sperm injection (ICSI) results. Do severe spermatogenic defects affect embryo quality or pregnancy rate? Further, does it matter in azoospermic patients whether the sperm source is testicular or epididymal? Our studies show there is no significant difference in results with ICSI related to any sperm count parameters either with patient's sperm or even with donor sperm. No matter how poor the sperm count, there was no difference from patients with high sperm counts nor even patients using donor sperm. There is no significant difference between results with epididymal sperm, either fresh or frozen, in comparison to results with ejaculated or donor sperm. However, both pregnancy rate and delivery rate were considerably lower with testicular sperm (testis sperm extraction) than with epididymal sperm (microsurgical epididymal sperm aspiration). This was true for overall results as well as in each category of the female partner's age. It is obvious that in all these cycles the female partner's age was the most important determinant of delivery rate, but testicular sperm always yielded lower results than epididymal sperm. These results show that it is the origin of the sperm rather than the spermatogenic defect that determines success rate with ICSI.
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http://dx.doi.org/10.3109/14647273.2010.534529DOI Listing
December 2010

Judaism and reproductive technology.

Authors:
Sherman J Silber

Cancer Treat Res 2010 ;156:471-80

Infertility Center of St. Louis, St. Luke's Hospital, St. Louis, MO, USA.

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http://dx.doi.org/10.1007/978-1-4419-6518-9_38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071555PMC
February 2011

To transplant or not to transplant - that is the question.

Cancer Treat Res 2010 ;156:41-54

Infertility Center of St. Louis, St. Louis, MO, USA.

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http://dx.doi.org/10.1007/978-1-4419-6518-9_4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086495PMC
February 2011

Role of semen analysis in subfertile couples.

Fertil Steril 2011 Mar 24;95(3):1013-9. Epub 2010 Mar 24.

Center for Reproductive Medicine, Academic Medical Center, Amsterdam, the Netherlands.

Objective: To evaluate the associations between the results of the male partner's semen analysis (classified according to the World Health Organization [WHO] criteria) and fathering a child without any treatment.

Design: Prospective multicenter cohort study.

Setting: Twenty subfertility centers in The Netherlands.

Patient(s): A total of 3,345 consecutive couples presenting for subfertility.

Intervention(s): None.

Main Outcome Measure(s): Associations between the results of the male partner's semen analysis, classified according to the WHO criteria, and fathering a child without any treatment within a time horizon of 1 year. Subsequently, we redefined semen quality criteria and reevaluated the associations.

Result(s): Follow-up data of 3,129 couples (94%) were available, of which 517 (17%) had a healthy pregnancy without treatment. The 1-year pregnancy rate in men with WHO normozoospermia did not differ significantly from that in men with WHO impaired semen (24% vs. 23%). In contrast, we observed lower chances of fathering a child for sperm concentrations <40 × 10(6)/mL, total sperm count <200 × 10(6), and sperm morphology <20% normal forms. With a multivariable regression model based on the redefined male semen subfertility criteria we were able to make a finer differentiation between subfertile men, with probabilities of fathering a child ranging from 7% to 41%.

Conclusion(s): The current WHO criteria for semen quality do not discriminate between fertile and subfertile men. Our redefined and graded semen criteria have strong predictive value. If interpreted correctly, the fast and inexpensive semen analysis remains the gold standard for defining a man's role in subfertility.
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http://dx.doi.org/10.1016/j.fertnstert.2010.02.024DOI Listing
March 2011

What's on the mind of IVF consumers?

Reprod Biomed Online 2009 Dec;19(6):767-9

During economic downturns demographers note that birth rates often decline as couples are more concerned with job security than providing for an additional child. The effects of economic conditions are likely to be amplified in infertile couples because there is often the need to pay for treatment. To try and understand changes in public interest in IVF over time, this study explored publicly available data (Google Insights) that reports changes in internet search activity relative to baseline volumes for search queries entered into Google search engines. Using the USA and the UK as case studies, it was observed that interest in internet searches using the term 'IVF' relative to searches within the infertility category remained relatively unchanged in the USA, with a small decrease observed in the UK. Internet searches using the combined terms 'IVF cost' and 'cost of IVF' have increased over the past 2 years relative to the infertility category. Additionally, inclusion of the term 'cost' appears concentrated in US states without insurance mandates compared with states with mandated insurance coverage. The extent to which Google internet search queries reflect public interest, and more importantly interest from infertile couples, is difficult to know for certain; however, there appears to be increased interest in the cost of treatment.
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http://dx.doi.org/10.1016/j.rbmo.2009.09.032DOI Listing
December 2009

Fresh ovarian tissue and whole ovary transplantation.

Authors:
Sherman J Silber

Semin Reprod Med 2009 Nov 5;27(6):479-85. Epub 2009 Oct 5.

Infertility Center of St. Louis, St. Luke's Hospital, St. Louis, Missouri 63017, USA.

A series of monozygotic (MZ) twin pairs discordant for premature ovarian failure presented an unusual opportunity to study ovarian transplantation. Ten MZ twin pairs requested ovarian transplantation and nine have undergone transplantation with cryopreservation of spare tissue. Eight had a fresh cortical tissue transplant, one of whom received a second frozen-thawed transplant after the first ceased functioning at 3 years. One had a fresh microvascular transplant. All recipients reinitiated ovulatory menstrual cycles and normal day 3 serum follicle-stimulating hormone levels by 77 to 142 days. Seven have already conceived naturally (three twice). Currently, seven healthy infants have been delivered out of 10 pregnancies. The oldest transplant ceased functioning by 3 years, but then she conceived again after a frozen-thawed secondary transplant. There was no apparent difference in return of ovarian function between the nine fresh ovarian grafts and the one frozen graft. Ovarian transplantation appears to restore ovulatory function robustly. Ten pregnancies, leading to seven healthy infants, including one after cryopreservation, bode well for application to fertility preservation.
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http://dx.doi.org/10.1055/s-0029-1241058DOI Listing
November 2009

Long-term economic benefits attributed to IVF-conceived children: a lifetime tax calculation.

Am J Manag Care 2008 Sep;14(9):598-604

Ferring International Center, St Prex, Switzerland.

Objective: To evaluate whether lifetime future net tax revenues from an in vitro fertilization (IVF)-conceived child are substantial enough to warrant public subsidy relative to the mean IVF treatment costs required to obtain 1 live birth.

Study Design: Mathematical generational accounting model.

Methods: The model estimates direct financial interactions between the IVF-conceived child and the government during the child's projected lifetime. In the model, we accrue IVF costs required to conceive the child to the government, and then we estimate future net tax revenue to the federal and state governments from this individual, offset by direct financial transfers from the government (eg, child allowances, education, Medicare, and Social Security). We discount lifetime costs and gross tax payments at Treasury Department rates to establish the present value of investing in IVF. We applied US Congressional Budget Office projected changes in tax rates over the course of the model.

Results: An IVF-conceived child, average in every respect (eg, future earnings, healthcare consumption, and life expectancy), represents a net positive return to the government. Based on an average employed individual born in 2005, the projected net lifetime tax contribution is US $606,200. Taking into consideration IVF costs and all direct financial interactions, the net present value is US $155,870.

Conclusions: Lifetime net taxes paid from a child relative to the child's initial IVF investment represent a 700% net return to the government in discounted US dollars from fully employed individuals. This suggests that removing barriers to IVF would have positive tax benefits for the government, notwithstanding its beneficial effect on overall economic growth.
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September 2008

Oocyte vitrification--women's emancipation set in stone.

Fertil Steril 2009 Apr 14;91(4 Suppl):1319-20. Epub 2008 Apr 14.

Reproductive Medicine Division, VU University Medical Center, Amsterdam, The Netherlands.

The techniques of vitrification of oocytes and the subsequent warming process being used today are now producing results far superior to the results that are obtained with slow-freezing techniques, and it would seem that this is the method of female fertility preservation that will be widely used in the near future. The reported success of the use of this method should stimulate a renewed debate on oocyte storage for fertility preservation without a medical indication.
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http://dx.doi.org/10.1016/j.fertnstert.2008.02.127DOI Listing
April 2009

Live birth following day surgery reversal of female sterilisation in women older than 40 years: a realistic option in Australia?

Med J Aust 2007 Sep;187(5):271-3

Discipline of Obstetrics and Gynaecology, University of Adelaide, Adelaide, SA, Australia, and Infertility Center of St Luke's Hospital, St Louis, MO, USA.

Objective: To determine the live birth rate following surgical reversal of sterilisation in women aged 40 years and older.

Design: Retrospective cohort study of pregnancy outcome following day surgery microsurgical reversal of sterilisation performed by two reproductive microsurgeons in the private sector.

Setting And Patients: 47 patients (aged 40 years or older) who had reversal of sterilisation performed between 1997 and 2005 in Adelaide, South Australia (n=35), or the Infertility Centre of St Louis, Missouri, USA (n=12).

Main Outcome Measures: Independently audited live birth surviving the neonatal period.

Results: Of the 47 patients on whom follow-up was obtainable from the two centres, 19 (40%) had a live birth, 7 had had only a first trimester miscarriage at the time of follow-up, and 21 (44%) had failed to conceive. Age at conception ranged between 40 and 47 years. Two women had two live births following surgery. The total direct costs (Australian dollars, adjusted to 2005) in Australia were $4850 per treatment, and $11,317 per live birth. The corresponding direct cost of a single cycle of in-vitro fertilisation (IVF) in Australia has been estimated at $6940, with a cost per live birth of $97 884 for women aged 40-42 years and $182,794 for older women.

Conclusion: Previously sterilised women wanting further pregnancy should be offered tubal surgery as an alternative to IVF, as it offers them the opportunity to have an entirely natural pregnancy. In settings where IVF is financially supported by government agencies or insurance, tubal reversal is a highly cost-effective strategy for the previously fertile woman.
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http://dx.doi.org/10.5694/j.1326-5377.2007.tb01240.xDOI Listing
September 2007
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