Joseph D. Schulman, MD
Dr. Schulman currently serves as the Chairman of the Institute’s Board of Directors and was Chief Executive Officer and Medical Director of GIVF from 1984 until 1998. He is internationally recognized in the fields of human reproduction and genetics and is the only American physician to have trained with Drs. Robert G. Edwards and Patrick Steptoe of Britain, the inventors of in vitro fertilization (IVF). Dr. Schulman was also the first director of the Medical Genetics Program at the National Institutes of Health (NIH), where he was a research scientist and served on the faculty for 10 years. He served as a consultant to numerous academic and research institutions, has produced over 500 original contributions to the medical literature, and has held an affiliate professorship at the College of Medicine of Virginia Commonwealth University, with an additional teaching appointment at the University of California San Diego.
Dr. Schulman is well known as one of the pioneers in creating the specialties of assisted reproduction and prenatal genetics in the United States, and was the impetus behind the development of many important concepts and techniques that have become standard in these fields.
After graduating from Harvard Medical School in 1966, Dr. Schulman initially trained in Pediatrics at Massachusetts General Hospital (1966-1968) and then did a Genetics fellowship at the NIH (1968-1970). While at NIH, he decided to specialize in the fields of human genetics and reproduction, and subsequently was fully trained in Obstetrics and Gynecology at the New York Hospital-Cornell Medical Center. He felt that the combination of all these disciplines would provide a unique foundation of formal qualifications for pursuing his medical and research interests.
Before commencing a research career at the National Institute of Child Health and Human Development (NICHD) at the NIH, Dr. Schulman became aware of the revolutionary research of Drs. Robert G. Edwards and Patrick Steptoe, who were working in England to develop the original methods for IVF. With the support of fellowships from the March of Dimes (obtained with the help of its eminent president, Dr. Virginia Apgar) and Harvard Medical School (Gilbert Fellowship) from 1973 through 1974, he worked directly with Drs. Edwards and Steptoe in Cambridge and Manchester, England. While there, he helped develop some of the first methods for obtaining and successfully fertilizing human eggs and cultivating human embryos in vitro (outside the body).
Returning from England in 1974, Dr. Schulman became the head of the Section on Human Biochemical Genetics at NICHD, where he remained until 1983. During his tenure at the NIH, he conducted extensive research and published numerous scientific papers on human genetic diseases and also founded and directed the NIH Inter-Institute Program in Medical Genetics.
After the birth of the first IVF babies in England, Dr. Schulman left NIH and started one of the first American IVF programs while becoming a Professor at George Washington University (GW). While at GW he hired Andrew Dorfmann as senior IVF embryologist. Their successful collaboration endured over two decades from their subsequent creation of GIVF with many significant accomplishments during that time as noted in our History of Excellence.
Before retiring from full-time active medical duty with the Institute, Dr. Schulman recognized yet another significant avenue for marrying the Institute’s broad medical and scientific capabilities with a market opportunity. In the late 1990s, GIVF established the first two modern IVF centers in China, first in Shanghai and then in Guangzhou. GIVF, which has always attracted international patients in search of treatment, was now able to take its capabilities beyond the United States.
As an obstetrician, pediatrician, geneticist, luminary in the field of human reproduction, and former research scientist, Dr. Schulman embodies what GIVF has come to represent and continues to catalyze innovations by studying the latest scientific developments.
Dr. Schulman published Robert G. Edwards: A Personal Viewpoint in 2010, a personal account of Dr. Schulman’s work with Nobel Laureate Robert Edwards on the development of the original methods of IVF. If you’d like to receive a free copy of Robert G. Edwards: A Personal Viewpoint, please send your name and mailing address to email@example.com.
Publications by Joseph D. Schulman, MD
by Joseph D. Schulman, MD
Robert G. Edwards was awarded the Nobel Prize in Physiology or Medicine, on October 4, 2010. Dr. Schulman reflects on firsthand involvement in certain aspects of the history of the very early development of human in-vitro fertilization pioneered by Robert G. Edwards, Patrick Steptoe, and Jean Purdy.
Bob Edwards was the world’s pre-eminent reproductive scientist. At last, after long delay, he has received the Nobel Prize in Physiology or Medicine which he so fully deserves. Louise Brown, the very first IVF baby, was conceived through Bob’s scientific achievements in 1977. Since then, several million healthy IVF babies have been born around the world.
Bob was a friend to me, and a consistent source of enlightenment and encouragement. The Institute which I founded in 1984, one the first IVF centers in the United States, was directly inspired by his example. Bob on three separate occasions crossed the Atlantic specifically to participate as keynote speaker in the Institute’s conferences for medical and research professionals. He was enthusiastic about MicroSort, a method of human preconceptual gender selection which we developed and told me he considered it one of the most important breakthroughs ever achieved in the field of human reproduction. Bob encouraged articles about MicroSort in his journals, and strongly advocated its utilization in Great Britain. In 2008, Bob, I, and other scientists were organizing a major international conference on reproductive bioethics in Washington, DC, but this effort was halted after he tragically became incapacitated by a rapidly progressive dementia.
Given the hugely important benefits that IVF has made possible for so many patients, benefits that were apparent to many in the field of medical science by the mid-1980s, why was the award of the Nobel Prize so long withheld that Bob Edwards’ principal IVF collaborator, surgeon Patrick Steptoe, was dead and Bob so ill that his wife, Ruth, had to take the call from Stockholm because he was unable to do so?
The fundamental reason the Nobel Prize award was delayed for decades was because Bob was a consistent fighter for reproductive innovation of many types. Indeed, it is not an exaggeration to call him the world’s most important leader in this effort. In the course of these activities, which ended only with his current illness, he faced much opposition and made powerful enemies. Bob led the fight against those who would restrict medical progress and inhibit personal reproductive freedoms. The original IVF research with human embryos which Bob pioneered in the 1970s was bitterly attacked by numerous scientists, religious leaders, politicians, bureaucrats, and members of the press. Cambridge Professor Martin Johnson, one of the first graduate students of Bob’s in the 1970s, described in 2009 how he was intimidated from any participation in IVF research: “We didn’t want to get too involved in it. The reasons for that were sheer level of hostility to the work…People were saying he really shouldn’t be doing this kind of thing…We were in this sort of little ghetto at the top of [the] Physiology [laboratory], which was ringed with prejudice and hostility and antagonism.” Opponents of Bob’s IVF work were influential enough to block support for his research from Britain’s Medical Research Council. Scientific opposition was widespread and included at least one Nobel Laureate. Foundation funding for Bob’s IVF research dried up. The antagonism and dearth of financial support nearly stopped the IVF work before it became successful. After the birth of Louise Brown, the nationalized British health care system refused to make IVF available to patients, and Bob was forced to find investors and open Bourn Hall with private funding. Only those who lived through these early years of IVF research can fully appreciate the immense determination – the sheer toughness – of Bob and Patrick, helped by their few allies including Bob’s department head at Cambridge, Professor C.R. (“Bunny”) Austin, and the dedicated nurse and laboratory technician, Jean Purdy. It all very nearly failed. As the Duke of Wellington was reported to have said after winning the Battle of Waterloo, “It was the nearest-run thing you ever saw in your life.” Without exaggeration, that statement could be accurately applied to the attainment of success with IVF.
The label of “controversial” has continued to surround Bob Edwards for the rest of his life. In his later years he passionately advocated the value of stem cell research, including research using embryonic cells. He strongly supported MicroSort in England, organized a conference at the Royal Society which included it, and was delighted that a Parliamentary committee reported favorably on it. His tragically delayed Nobel award is one of the prices he paid for such determined and publicly visible efforts.
The struggle to bring reproductive innovation to patients, and to advance reproductive science, still continues. To this day – over 30 years after the birth of Louise Brown – our own government still prohibits the National Institutes of Health from funding any research on human IVF, and all advances in the IVF field in the United States have been accomplished entirely without government support. The Vatican is still an opponent of IVF, and officially expressed its dismay at the awarding of the Nobel Prize to Dr. Edwards. Despite millions of IVF births, laboratories performing IVF have in the last few years been shut down in Italy. Despite Bob’s strong support of MicroSort and the many normal births already achieved by this method of preconceptual gender selection, MicroSort is not today available to patients in England. And whether or not it will become widely available for patients in the United States will be influenced by the pending decisions of federal regulators.
Continued progress in the science and medicine of human reproduction is, in the long run, absolutely certain. And history has shown, as with IVF, that initially controversial medical advances ultimately become both widely adopted and wisely utilized. However, delaying such advances through restriction of research funding or denial of clinical access harms some patients irreversibly. Individuals, particularly females, have a time-limited window in which to exercise their reproductive choices. Time matters to all patients who seek reproductive assistance. That Robert G. Edwards was denied the Nobel Prize for several decades is a vivid proof of the legal truism, attributed first to William Gladstone, that “justice delayed is justice denied.” With equal justice it may be said that “medical innovation delayed is medical innovation denied.” As someone who has participated actively in medical progress for over forty years, I hope that the future will bring more innovation and less denial than in the past. The combined efforts of physicians, scientists, and men and women of goodwill both inside and outside of government are required for this to happen.
by Joseph D. Schulman, MD
Joseph D. Schulman, MD, a former medical school professor and head of the Inter-Institute Medical Genetics Program at the National Institutes of Health and is the Founder and Chairman of the Board of Directors of the Genetics & IVF Institute. Dr. Schulman offers a candid interpretation of the efforts and complexity behind medical progress. This book highlights challenges to innovation in the reproductive sciences and the difficulties in moving laboratory breakthroughs into widespread medical use. Dr. Schulman worked with Professor Edwards and Mr. Steptoe in England for an entire year in the 1970s on the development of the first successful human IVF methods. He is the only American scientist or physician to have had the privilege of such participation.
The following article was published in Clinical Genetics, February, 1996.
JOSEPH D. SCHULMAN (1,3), SUSAN H. BLACK (1,3) ALAN HANDYSIDE (2) AND WALTER E. NANCE (3)
Genetics & IVF Institute, Fairfax, Virginia (1), Human Embryology Group, Institute of Obstetrics and Gynecology, Hammersmith Hospital, London (2), and Department of Human Genetics, Medical College of Virginia, Richmond, Virginia (3).
Keywords: antenatal diagnosis, dominant traits, Huntington disease, in vitro fertilization (IVF), Preimplantation Genetic Testing (PGT), genetic disease prevention
Genetic testing for serious dominantly inherited traits for which there is no effective treatment is an excellent example of the difficult and sometimes unexpected dilemmas that the application of genetic technology can raise. In this situation, the natural desire of patients to avoid the transmission of a genetic disease to their children may conflict with and be completely extinguished by the adverse effects of presymptomatic diagnosis in the at-risk parent. In the case of Huntington disease, this dilemma has led to the development of elaborate protocols to ensure that at-risk individuals understand and are emotionally competent to accept all of the implications of presymptomatic diagnosis. In practice, only a minority of adults who are at risk elect to have presymptomatic testing (Quaid & Morris, 1993; Craufurd et al., 1989). As a consequence, the enormous potential of antenatal diagnosis to reduce the burden of genetic disease in the population, as well as the tragedy of recurrent cases within a family, is seldom realized. Fortunately, preimplantation genetic testing (PGT) now provides an approach in which antenatal diagnosis can be offered without incurring the adverse effects of the presymptomatic diagnosis. We believe this approach should be reviewed along with other relevant reproductive options when counseling patients at risk for Huntington disease and possibly other dominantly inherited traits as well.
PGT refers to a group of related technologies in which in vitro fertilization (IVF) is used to produce early embryos which are then biopsied, often as early as the 4 cell stage, to permit genetic testing of the embryos by PCR-based methods. Although the reliable amplification of target regions of the genome in single cells is still a technical challenge, prenatal diagnoses have been accurately made by this method without recognized adverse effects on the fetus (Harper & Handyside, 1994). For patients who are at high risk (typically 50%) of carrying a gene for Huntington disease, PGT offers a way in which they can participate in antenatal genetic testing without incurring the emotional, social and financial burdens that might result from the presymptomatic disclosure of their own carrier status. Such patients could be offered the option of having IVF with preimplantation biopsy and testing of their embryos without ever being informed of the specific test results. The couples would be told only that embryos were formed and tested, and that only apparently disease-free embryos were replaced in the uterus (and, if sufficient numbers were available, frozen for subsequent pregnancy attempts). The parents would specifically not be given any information about the number of eggs obtained, the number of embryos formed, the number surviving biopsy, the number in which diagnosis was successful, etc. In other words, no information would be given which might provide a basis for inferring whether or not any embryos with the Huntington gene were ever identified. Hence, parents would derive no direct or indirect information about their own genetic risk, while PGT, if performed accurately, could reduce the fetal risk to zero.
While we believe that this approach to the management of Huntington disease offers enormous potential benefits, it raises several important issues. First, it is apparent that IVF and PGT would be offered to some couples in whom the at-risk parent was actually unaffected and this could be construed as an inefficient or “wasteful” use of an expensive technology. However, since presymptomatic diagnosis is not the goal of the testing, redundant testing must be regarded as part of the cost of disease prevention by this approach. Second, accurate diagnosis on single cells removed from embryo biopsies is a technically challenging procedure, especially for other triplet repeat disorders such as fragile X (Black, 1994; Levinson et al., 1994; Ray and Handyside, 1995), and for dominant disorders where allele dropout is a particular risk. These concerns may be addressed through rigorous methodology such as the replacement of embryos only when the independent amplification of two blastomeres gives concordant normal results, or the possible use of blastocyst (multicell) biopsy. Third, scrupulous attention to confidentiality and careful genetic counseling with fully informed consent would obviously be required. None of these issues, however, would appear to be insurmountable.
In principle, the same conceptual approach may be applicable to other late onset dominant disorders such as Charcot-Marie-Tooth disease, certain familial cancers, and possibly even Alzheimer’s disease. IVF and PGT would emerge as important approaches for the management of such diseases.
This proposal also has important public health implications. In Huntington disease, nearly all cases arise in pre-existing Huntington families rather than as new mutations. These procedures therefore constitute a potentially effective strategy for greatly reducing or even eliminating Huntington disease from the population. IVF is now a widely accepted reproductive option. On the average, 2-3 IVF cycles are required to achieve a live birth in the best programs. In the U.S., IVF with PGT is available for about $10,000 per treatment cycle, and less in some other countries. Hence, for an average cost of about $50,000, a couple containing one member at risk for having the Huntington gene could be on average assured of having two unaffected children and the risk of the disease in all future generations would be eliminated.
If this opportunity were to be provided on a voluntary basis to all at-risk couples, the gene frequency in the population could over several generations be dramatically reduced. The costs in any given generation as well as the cumulative benefits and cost savings to all future generations would be gradually realized.
In one of its crowning scientific achievements, mankind has succeeded in eradicating certain infectious diseases such as smallpox, which is now considered officially to be absent worldwide. Perhaps it is not too early to consider the elimination of Huntington disease and other extremely deleterious dominant traits as a goal for the 21st century. This proposal is based on our assumption that many patients at risk for Huntington disease would seize the opportunity to prevent transmission of the trait to their children if this could be done without disclosure of their own disease status. We do not know that our assumption is correct. but it is clearly a researchable issue that could lead to the initiation of voluntary programs to confirm the effectiveness and acceptability of PGT for this disease.
Black, S.H. Preimplantation genetic diagnosis. Current Opinions in Pediatrics 1994: 6, 712-716.
Craufurd D., Dodge A., Kerzin-Stovvar L., Harris, R. Uptake of presymptomatic predictive testing for Huntington’s disease. Lancet 1989: 2, 603-605.
Harper, J.C., Handyside A.H. The current status of preimplantation genetic diagnosis. Curr Obstet Gynecol 1994: 4, 143-149.
Levinson, G., Sisson, M.E., Harton, G.L., Palmer, F.T., Fields, R.A., Black, S.H., Fugger, E.F., Maddalena, A., Schulman, J.D. Preimplantation genetic testing for X-linked disorders and cystic fibrosis. 7th Int. Conf. on Early Prenatal Diagnosis, Jerusalem, May, 1994.
Quaid K.S., Morris M. Reluctance to undergo predictive testing: the case of Huntington disease. Am J Med Gen 1993: 45, 41-45.
Ray, P.F., Handyside, A.H. Increasing the denaturation temperature during the first cycles of nested amplification reduces allele dropout from single cells for preimplantation genetic diagnosis. Molecular Human Reproduction, submitted, 1995.
Learn more about Preimplantation Genetic Testing (PGT)
The following article was published in Neurology, September, 1999.
L. Fallon, G.L. Harton, M.E. Sisson, E. Rodriguez, L.K. Field, E.F. Fugger, M. Geltinger, Y. Sun, A. Dorfmann, C. Schoener, D. Bick, J. Schulman, G. Levinson, S.H. Black
First published September 1, 1999, DOI: https://doi.org/10.1212/WNL.53.5.1087
Preimplantation Genetic Diagnosis for Spinal Muscular Atrophy Type 1
Reprinted from The Cancer Journal from Scientific American. Copyright (c) 1997 Scientific American. All rights reserved.
Editorial: “A New Perspective”
Michael S. Opsahl, M.D., Edward F. Fugger, Ph.D., Richard J. Sherins, M.D., and Joseph D Schulman, M.D.
In the past 3 years, the introduction of two new technologies has revolutionized the opportunities to preserve reproductive options for both men and women who are diagnosed with cancer. These involve the use of in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) after semen cryopreservation for men, and autotransplantation of gonadal tissue after ovarian tissue cryopreservation in women. Improved survival rates in cancer victims bring new awareness of and interest in quality-of-life issues such as reproduction. Broadening awareness of these options in the oncology community is the primary purpose of this editorial.
ICSI AFTER SPERM CRYOPRESERVATION
Semen freezing with appropriate cryoprotectants prior to initiating cancer therapies likely to destroy future sperm production has been utilized for some years. As conventionally provided, however, this strategy has several limitations. Semen of some men does not cryopreserve well (Genetics & IVF Institute, unpublished data), and the reduction or near absence of sperm survival in thawed specimens can be a significant limitation on subsequent pregnancy attainment by intrauterine insemination (IUI) or conventional IVF. This may be a particular problem for men newly diagnosed with lymphoma or testicular cancer whose semen frequently has poor quality prior to the institution of chemotherapy, radiation, or genital surgery (1). To provide an adequate reserve of samples for future use, semen is usually collected over a period of 1 to 2 weeks. Delays of this magnitude before initiation of cancer therapy are often considered undesirable, so it is common to have very few semen specimens stored before treatment begins. The reduced number of inseminations that can be undertaken with limited stored semen, and the frequently marginal quality of the specimens, contribute to enormous stress and, in many cases, later reproductive failure for affected couples.
The advent of ICSI has markedly enhanced the ability to preserve reproductive options for many men with newly diagnosed cancer. ICSI is a variation of IVF in which a single sperm is microinjected into each egg obtained from the woman after stimulation of her ovaries with godadotropins and transvaginal, nonsurgical, ultrasound-guided egg retrieval. ICSI was developed in Brussels in 1992 by Van Steirteghem, Palermo, and coworkers (2). It has proven to be an extraordinarily useful technology for treatment of severe male infertility (3), and thousands of pregnancies worldwide have now been achieved (4). So powerful is this option that couples have actually been able to attain pregnancies when the husband’s sperm production was so abnormal that fewer than 10 living sperm could be identified for use in microinjection! With a woman in her early to mid thirties, pregnancy rates achieved by leading ICSI teams approximate 30% per treatment cycle but can be higher in younger women producing larger numbers of embryos. There have also been many ICSI pregnancies in women in their early forties (3,4). However, if the cancer patient’s female partner is in her mid forties or beyond, oocyte factors usually will require the use of oocyte donation (Donor Egg IVF) for pregnancy attainment with ICSI (5). Remarkably, pregnancy rates with ICSI therapy are virtually independent of the degree of semen abnormalities, freeze/thaw quality of the semen, and number of available sperm (3,6).
The implications of ICSI for men with newly diagnosed cancer are dramatic. There is almost always enough time to obtain at least one semen sample before starting treatment for malignancy. A single ejaculate, even if of poor quality, will usually contain at least a few million living sperm. A cryobank experienced at working with sperm for ICSI can take a single ejaculate, add cryoprotectant, and freeze the specimen in a large number of very small aliquots containing a few thousand sperm each. Usually, only one of these many aliquots is needed to provide enough living sperm for one ICSI cycle. Thus, a single ejaculate will usually provide sufficient sperm for any number of future attempts at ICSI. Of course, if time before therapy permits it, additional semen samples can be frozen so that pregnancy can be attempted initially with intrauterine inseminations, with ICSI as a backup option if this simpler strategy fails.
In a subset of male patients, ejaculatory or erectile dysfunction may occur as a result of extensive pelvic and/or retroperitoneal surgery (from testicular, bladder, and prostate cancer), which interrupts neurological control of genital function. Sperm production is preserved in many such men, but they cannot mechanically deliver sperm from the epididymal reservoir to an ejaculate. With ICSI, it is now possible to achieve high fertilization and pregnancy rates using sperm obtained directly from the epididymis or testis via surgical extraction (6) and recently by non-surgical needle aspiration (7) under sedation in an outpatient setting.
ICSI now provides an important reason to encourage semen cryopreservation of at least one ejaculate before initiating cancer treatment in nearly every male whose future reproductive function is likely to deteriorate afterward. This has great and obvious value for men who indicate a clear desire to have children in the future.
Cryopreservation of semen for possible future ICSI is so simple and inexpensive that it may also be worth considering by males with less clear-cut future reproductive goals, including men who have apparently completed their families and are planning vasectomy; their desires may change, and factors such as future remarriage or even the death of a child cannot be excluded.
AUTOTRANSPLANTATION OF CRYOPRESERVED OVARIAN SLICES
Women of reproductive age with newly diagnosed cancer may suffer irremediable oocyte destruction from many therapeutic regimens. In the past, the only option to have a biological child with a woman’s own eggs was to rapidly perform an IVF cycle and then cryopreserve the resulting embryos for future transfer. That strategy has substantial disadvantages. It is not applicable to women who are not currently married or with a long-term partner, and it is inappropriate for women with an estrogen-sensitive cancer. Additionally, an IVF cycle usually takes 2 to 3 weeks to initiate and complete (8), causing unacceptable delays for many types of cancer treatment. Furthermore, cost is high at a time when financial stress on the family is maximal. Clinical experience also suggests that women with cancer frequently have unusually poor IVF cycles. Perhaps most important, even if the IVF cycle is of typical quality, the number of embryos obtained is limited (seven to eight on average), and the probability that these embryos, when thawed and transferred to the uterus several years later, will produce a pregnancy is not likely to exceed 40% to 50% (8). The limitations of this method of preserving female reproduction after cancer diagnosis are so substantial that the IVF strategy, though available for over a decade, has only been utilized by a small number of women.
Research on ovarian tissue cryopreservation by Professor Roger Gosden and colleagues in Great Britain now offers the possibility for a much more desirable approach to preserving future reproductive potential. Gosden has shown in experimental animals that ovaries can be removed and thin slices of the ovarian cortex preserved by freezing (9). These cortical slices each contain many thousands of eggs (10). The slices can subsequently be thawed and replaced into the region of the residual ovarian site near the normal fimbriated end of the fallopian tube. Since these are autografts, there is no immunological graft rejection. Sheep so treated have subsequently gone on to have normal ovulatory cycles for at least 2 years, and most important have conceived and borne normal offspring after spontaneous intercourse (9,11). Eggs in slices of human ovarian tissue survive cryopreservation and thawing like animal ovaries (12; Genetics & IVF Institute, unpublished data). It is likely, but not certain, that ovarian tissue from female children can also be cryopreserved like adult ovarian tissue, since all oocytes are fully formed in human beings before birth and remain arrested in meiosis until recruited for ovulation in a given menstrual cycle. The oocytes from children might, in fact, have a higher survival since a greater proportion are primordial follicles, which survive cryopreservation better than more advanced follicles.
Because of this highly important set of observations in experimental animals and the corresponding substantial likelihood that ovarian tissue cryopreservation and autotransplantation will be successful in human beings, Institutional Review Board-approved clinical trials by Gosden’s team and our own group are now in progress in women with newly diagnosed cancer. With written informed consent, the specific protocol involves removal of one or both ovaries by minilaparotomy or laparoscopy, and cryopreservation of as many separated cortical slices as can be obtained. Several patients in Great Britain and in the United States have now had ovarian cryopreservation performed, but replacement of ovarian tissue has not yet been undertaken. Replacement of grafts is expected within the next 1 to 2 years, as soon as the primary cancers have been successfully treated and the physicians tell their patients that they can attempt pregnancy.
Given the limited alternatives for women of reproductive age with cancer who may lose their future fertility potential, and the extraordinary results summarized above, ovarian cryopreservation will likely prove clinically useful; this will be a revolutionary improvement in the care of women with cancer. While we recognize as scientists that there can be unanticipated barriers to success with any new reproductive technology, the potential benefit outweighs the limited risks. From initial experience, ovarian cryopreservation appears to be an option of great interest to many women with newly diagnosed cancer, and these women often consider their risk of participation in this protocol to be minimal with the possibility of retaining both normal fertility and hormonal function.
In summary, sperm cryopreservation for future ICSI and ovarian tissue cryopreservation for future autotransplantation are new opportunities to preserve reproductive options of great importance to patients with newly diagnosed cancer. Since patients must utilize these strategies before cancer therapy is initiated, and these patients will not have a future chance to benefit once therapy has damaged gonadal function, awareness of these technologies among oncologists, radiation therapists, and other colleagues who interface with the victims of cancer is a high priority.
- Sanger WG, Olson MS, Sherman, JK. Semen cryobanking for men with cancer. Fertil Steril 1992;58:1024-1027.
- Palermo G, Joris H, Devroey P et al. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 1992;340:17-18.
- Sherins RJ, Thorsell LP, Dorfmann A. et al. Intracytoplasmic sperm injection facilitates fertilization even in the most severe forms of male infertility: pregnancy outcome correlates with maternal age and number of eggs available. Fertil Steril 1995;64:369-375.
- Bonduelle M, Legein J, Buysse A et al. Prospective follow-up of 423 children born after intracytoplasmic sperm injection. Hum Reprod 1996;11:1558-1564.
- Sauer MV, Paulson RJ, Ary BA et al. Three hundred cycles of oocyte donation at the University of Southern California: assessing the effect of age and infertility diagnosis on pregnancy and implantation rates. J Assist Reprod Genet 1994;11:92-96.
- Nagy Z, Cecile J et al. Using ejaculated, fresh, and frozen-thawed epididymal and testicular spermatozoa gives rise to comparable results after intracytoplasmic sperm injection. Fertil Steril 1995;63:808-815.
- Sherins RJ, Belker AM, Coulam CB et al. Percutaneous nonsurgical sperm aspiration (NSA) from the testis: a highly effective diagnostic and treatment method to achieve pregnancy in azoospermic men. Presented at the Fifty-Second Annual Meeting of the American Society of Reproductive Medicine; November 4, 1996: Boston, MA.
- Tan SL, Royston P, Campbell S et al. Cumulative conception and livebirth rates after in-vitro fertilization. Lancet 1992;339:1390-1394.
- Gosden RG, Baird DT, Wade JC et al. Restoration of fertility to oophorectomized sheep by ovarian autografts stored at -196 degrees C. Hum Reprod. 1994;9:597-603.
- Faddy MJ, Gosden RG. A model confirming the decline in follicle numbers to the age of menopause in women. Hum Reprod 1996;
- 11:1484-1486. 11. Baird DT, Webb R, Campbell B et al. Autotransplantation of frozen ovarian strips in sheep results in normal oestrous cycles for at least 22 months. Presented at the Twelfth Annual Meeting of ESHRE;July 2, 1996:Maastricht, Denmark.
- Newton H, Aubard Y, Rutherford A. et al. Low temperature storage and grafting of human ovarian tissue. Hum Reprod 1996;11:1487-1491.
Copyright (c) 1997 Scientific American, Inc.
From the Genetics & IVF Institute, Fairfax Cryobank, Fairfax, VA and the Medical College of Virginia, Richmond, Virginia.
Advances in Assisted Reproductive Technology (ART) have revolutionized the management and care of couples facing infertility or increased risks for genetic conditions. Most recently, an application of ART has included the option of family balancing, or increasing the chance of a having a child of a particular gender due to a family history of a sex-linked genetic disease or the under-representation of a gender within one family.
At the Genetics & IVF Institute (GIVF), headquartered in Fairfax, Virginia, USA, ART treatment options for infertility, genetic diagnosis and family balancing are available. In fact, world-renowned for its pioneering work in infertility and genetics, GIVF developed or perfected many of the treatments and techniques used today in other centers and is responsible for over 14,000 pregnancies worldwide.
MicroSort®, an exclusive preconception technology developed by GIVF, uses flow cytometry to separate semen into specimens enriched in male or female-producing sperm. These samples are then used in conjunction with intrauterine insemination or in-vitro fertilization (IVF). GIVF reported the first human births in the world following Microsort® for X (female) and for Y (male). The MicroSort® process is currently in a US government approved clinical trial and its use by couples requires meeting specific criteria and informed consent. MicroSort® has been performed successfully for families such as those at risk for Duchenne Muscular Dystrophy and Alport syndrome, and is increasingly popular among couples who already have a child of a particular gender.
Another highly technical reproductive technology offered at GIVF is Preimplantation Genetic Diagnosis (PGD). Couples wishing greater accuracy in the prevention of sex-linked disease or for family balancing can use PGD. PGD is a form of genetic diagnosis performed on early embryos prior to implantation in the uterus and initiation of pregnancy. When using PGD, only embryos determined to be genetically unaffected for a condition or of a particular gender are returned to the uterus, and the accuracy of the testing is as high as 99%. As one of the first laboratories to pioneer PGD technologies, the PGD lab at GIVF has extensive experience and success with early diagnosis.
The application of PGD is also widely used for couples wishing to avoid initiation of a pregnancy with abnormal chromosomes or a specific disease such as Spinal Muscular Atrophy and Cystic Fibrosis. Each IVF cycle in which PGD has been performed has a better potential outcome, since embryos screened have been shown to have a lower spontaneous loss rate and a reduced risk of abnormal offspring (i.e. Down syndrome). MicroSort® can be combined with PGD to increase the number of embryos of a desired gender available for transfer.
With greater demand for treatment due to technological advances, the needs of patients presenting for evaluation, treatment and counseling are becoming increasingly diverse and complex. MicroSort® and PGD are cutting edge reproductive technologies that many couples are rapidly electing. Expansion of ART applications are expected to continue as patient demands increase with greater global awareness of their potential benefits.
Learn more about Preimplantation Genetic Testing (PGT)
The following article a collaboration between GIVF and Harvard Stem Cell Institute
John Dimos and Kevin Eggan
07 March 07
Derivation of Embryonic Stem Cells From SMA Affected Embryos