The International Council on Infertility Information Dissemination, Inc

Ovarian Cryopreservation by Michael Opsahl, MD

Ovarian Cryopreservation 
by Michael S. Opsahl, MD 

 
Cryopreservation of ovarian tissue is a technique to bank oocytes (eggs) in situations where the woman may lose all her eggs from a medical treatment, disease process or even the natural loss from natural aging. Potential uses for this technique include restoring fertility and normal ovarian hormone production without the use of medications. The technique of ovarian tissue cryopreservation and transplantation of the thawed tissue is experimental. Since the first significant publication on ovarian tissue cryopreservation and transplantation in 1994(1), over 100 publications attest to the scientific interest in this technique or treatment strategy.(2-36)

Background

Several diseases and their treatments threaten to destroy all the eggs in a woman's ovaries. Diseases rarely have a direct effect on the eggs in the ovary. Exceptions include genetic disorders such as women with a single X chromosome (Turner Syndrome) or women missing a specific piece(s) of an X chromosome, in which case the eggs die quickly and the women have premature menopause. Chemotherapy or radiation used to treat cancer or some non-cancerous disorders have the unfortunate side effect of destroying the eggs in the ovary as well as the diseased cells.

Unlike sperm production in men which is continuous, women are born with all their eggs and they do not produce any more. The natural process of each menstrual cycle consumes approximately 500-1000 eggs until the supply is exhausted (about age 51, menopause). Any treatment that accelerates the loss of eggs threatens to decrease fertility and will cause menopause at an earlier age than expected. Surgery to remove all or a portion of one or both ovaries, some chemotherapy (cyclophosphamide, doxorubicin, vinblastine, etc.), and radiation therapy all have known toxic effects on eggs. The number of eggs that die from these treatments depends primarily on the agent(s), the dose, and the age of the woman when treated. The higher the dose and the older the woman, the more likely that most eggs will be lost and that menopause will occur.

Men have been able to cryopreserve (freeze) their sperm for decades. However, women have not been able to freeze their eggs reliably because the eggs are hard to retrieve and unfertilized eggs have generally not survived freezing. With the advent of IVF, egg or embryo freezing became possible. IVF has several significant limitations. IVF takes time to complete since the hormones used to stimulate the ovary are administered at specific times of the menstrual cycle and then are administered for 2-4 weeks. Many cancer patients must begin their cancer treatment before IVF can be completed. Many cancer patients are young and unmarried; therefore, they do not have a partner to provide sperm to fertilize the eggs. Cryopreservation of unfertilized eggs is an alternative that has gained interest with newer freezing techniques and there are successful pregnancies. Further, IVF is medically inappropriate for many women with hormonally responsive tumors such as breast cancer. The ovaries can be surgically moved from the field of radiation in selected cases but this technique does not help women with chemotherapy.

Ovarian hormone suppression (gonadotropin releasing hormone agonist) during chemotherapy significantly protected human eggs in one research study. Follow-up studies by other centers and with larger numbers of women will clarify the value of this approach. Gonadotropin releasing hormone agonist administration is inexpensive, relatively safe and unlikely to compromise other treatments; therefore, it deserves serious consideration despite limited data on its effectiveness. Donor eggs, for those women who have irreversible ovarian failure, provide very high rates of successful pregnancies, if other options fail.

Perhaps the largest group of women who may benefit from egg banking, are those women who delay child-bearing, for whatever reason, until the late thirties or forties. It is widely recognized that female reproduction becomes progressively more inefficient with advancing age and pregnancies are quite rare by the mid-forties. Whether, egg banking at an early age will be practical or effective remains speculative.

For all these reasons, a technique to bank eggs would allow women to have the same reproductive options as men when faced with a serious disease that threatens to destroy their eggs.

 

Dr. Roger Gosden's published paper in Human Reproduction in 1994 demonstrated the ability to cryopreserve ovarian tissue, transplant it after thawing and obtain functioning ovarian tissue that led to successful births of healthy animals.(1) His team also demonstrated long-term functioning of transplanted cryopreserved ovarian tissue for about two years in sheep.(21) The fertility rate after ovarian cryopreservation in mice was approximately 50 - 75% after ovarian tissue autotransplantation.(27;33) Human tissue was viable after transplantation into a mouse model.(9;15;29) Whether human results will be as successful as animal results will require time and experience. Consequently, until clinical trials demonstrate the viability of this technique, ovarian tissue cryopreservation and transplantation must be considered highly experimental.

Based on preliminary animal data, human trials of ovarian tissue cryopreservation began in 1995.(30) These ongoing trials have produced limited human data since humans often require many years to be free of cancer, or they may not have partners and may not be ready for pregnancy.

 

Techniques

Ovarian tissue cryopreservation begins with laparoscopy or mini-laparotomy. Ordinarily, the surgeon removes only one ovary to allow normal ovarian hormone production from the other ovary during treatment and because the woman may have ovarian function after treatment of her disease. The laboratory staff portion sections the ovarian cortex (which contains the eggs) into thin tissue slices. The tissue slices are cryopreserved at -196°C using specialized cryoprotectants and controlled-rate freezing equipment.

When the woman and her physicians feel fertility is appropriate, transplantation of the ovarian tissue strips can be attempted. 

In animals and humans, frozen ovarian slices have a high survival rate after thawing. The location for tissue transplantation could be in the abdomen near the fallopian tube to allow natural ovulation and conception. Natural conception occurred in all animal studies. The ovarian tissue began to function within several months after transplantation. The disadvantage of transplantation into the abdominal cavity is limited access, potentially lower viable tissue since ingrowth of blood vessels occurs primarily from only one side of the tissue, and adhesion formation (scar tissue) during the recovery period after surgery.

Recently, transplantation of human ovarian tissue into the forearm resulted in follicle formation and egg retrieval with a needle. Parathyroid tissue transplanted into the forearm routinely functions normally in patients with other medical disorders. The forearm is well-vascularized, easy to access, and is a site with little surgical risk. Consequently, because the ovarian tissue is surrounded with vascularized tissues, it may have a greater probability of short and long-term function. Transplantation of tissue into the forearm precludes natural conception. Assisted reproduction with IVF using eggs retrieved from the arm would necessarily be applied. Risks Surgery is necessary to remove the ovary. Despite routine surgical and anesthetic techniques, complications invariably occur but they are uncommon. The risks are no greater for this procedure than are the risks for any other patient who undergoes ovary removal. If the patient has cancer, the oncologist should address any pre-operative medical needs.

Most cancers do not spread (metastasize) to the ovary. However, if cancer cells are in the ovarian tissue at the time of cryopreservation, they may survive freezing and thawing and they will be transplanted with the normal ovarian tissue. Transplantation of tumor containing ovaries resulted in cancer in the recipient animals. (36) You should ask your doctor for his/her opinion about the likelihood of metastatic cancer cells in the ovary.

Usually, pathology evaluates a sample of the excised ovary. However, the sample is insufficient to confirm a cancer-free ovary. In selected cases, researchers may be able to stain a small portion of the ovarian tissue for cancer markers that to detect tumor cells before transplanting the tissue strips. Other researchers explored the possibility of growing a sample of the ovarian tissue in an immune-deficient mouse to detect occult cancer in the tissue.

Most oncologists believe transmission of cancer cells should be very remote; however, the possibility is real and collaboration between the oncologist and the reproductive surgeon is essential to minimize this risk.

Currently, the process requires removal of all or a part of an ovary and less often both ovaries. The oophorectomy, by definition, will remove 50% of the woman's eggs. It follows that this should increase the probability of menopause from the chemotherapy or radiation to follow if one believes that menopause occurs earlier in women with fewer eggs. Available research suggests that complete removal of an ovary before age 30 accelerates the age of onset for menopause to 44 years, on average. Removing an ovary after age 30 has less effect, incrementally, on menopause.(37-39)

 

Future Directions

Any number of questions remain unanswered, but of critical importance, to bring this technique into mainstream use. For example: How long can the tissue remain frozen and still function after thawing?, Where is the best location to transplant the tissue strips?, How much ovarian tissue is required to provide enough eggs for successful pregnancy?, How long will the tissue function after transplantation?, and many more.

A very interesting avenue of research involves the growth of ovarian tissue from one species in another species (xenograft).(5;6;9;11;15;26) If this technique works and proves safe, several problems become less of an issue.

First, tissue grown in another animal prevents cancer in the human recipient. Even patients with ovarian cancers may be able to use this technique to recover normal eggs without any associated cancer cells. Second, the ovarian tissue contains a limited number of eggs. A xenograft may allow more efficient maturation and retrieval of eggs for IVF. Third, the limited tissue strips might be used more gradually over time for additional children.

Fourth, if only small amounts of tissue prove adequate for IVF, then a small biopsy of tissue in a young woman may be a means of banking eggs if she later finds herself infertile.

Another line of research is egg freezing. Ovarian stimulation similar to IVF allows egg retrieval. The eggs are frozen before they are inseminated and fertilized. Subsequently, when the time is right, the eggs are thawed and inseminated. Embryos derived from cryopreserved unfertilized eggs have yield embryos that developed into normal children. The number of children is limited but growing and the number of successful births clearly exceeds that with ovarian tissue cryopreservation. Only a few centers offer this technique.

 

Questions to ask your doctor and yourself before consulting a reproductive specialist.

Q: What is the likelihood that sterility will occur after treatment? Most patients view their participation in experimental therapies differently when the risk of sterility is 10% versus 90%.

Q: What is the risk of cancer cells in the ovary at the time of ovarian cryopreservation? Clearly, if the risk of metastatic cancer in the ovary is high, this technique is probably not a good idea until methods of extracting the eggs from the tissue without transplantation are available.

Q: How much time do you have before cancer therapy begins? With limited time (less than one month), IVF is impractical but surgery can be performed very quickly - within a few days if necessary. With more time, IVF for production of eggs or embryos is a realistic option.

Q: Are you single or married? Single women have less reason to pursue IVF and embryo cryopreservation unless they have a partner. Embryos formed with donor sperm may be less desirable for producing a family when later a woman finds a partner. Egg freezing may be a better option for single women. Women with a partner should consider IVF and freezing embryos. The woman may want to retain sole control of the embryos once they are frozen. Occasionally, marriages or relationships fail and the former partner could prevent the embryos from being used if the couple agrees to joint control of the embryos.

Q: Do you have a tumor sensitive to reproductive hormones? Women with breast cancer, for example, probably do not want to risk stimulation of their cancer from the high estrogen levels generated during IVF. Nevertheless, many breast cancer survivors can become pregnant safely, so some method of conserving their eggs seems reasonable.

Q: Are you willing to be part of a highly experimental research protocol? Until more experience is available, your participation in ovarian tissue cryopreservation places you on the cutting edge of science. Participation involves risks, known and unknown, and likely expenses that are not covered by insurance. If you are a healthy woman who wants to delay conception and pregnancy for any reason, the experimental and uncertain success of ovarian tissue cryopreservation makes this a very controversial technique for you. In addition to the experimental aspects of participation, the act of removing all or a portion of an ovary may actually increase the probability of an earlier menopause, which is counter-productive to the reason for participating.

Michael Opsahl, M.D. retired from a prestigious career in the United States Navy in 1994 and joined the Genetics & IVF Institute. Dr. Opsahl is board certified in Obstetrics and Gynecology and Reproductive Endocrinology.

 

Selected scientific articles:

1. Gosden RG, Baird DT, Wade JC, Webb R. Restoration of fertility to oophorectomized sheep by ovarian autografts stored at -196 degrees C. Hum Reprod 9[4], 597-603. 1994. 
2. Wang H, Mooney S, Wen Y, Behr B, Polan ML. Follicle development in grafted mouse ovaries after cryopreservation and subcutaneous transplantation. Am J Obstet Gynecol 187[2], 370-374. 2002. 
3. Salle B, Demirci B, Franck M, Rudigoz RC, Guerin JF, Lornage J. Normal pregnancies and live births after autograft of frozen-thawed hemi-ovaries into ewes. Fertil Steril 77[2], 403-408. 2002.
4. Schnorr J, Oehninger S, Toner J, Hsiu J, Lanzendorf S, Williams R, Hodgen G. Functional studies of subcutaneous ovarian transplants in non-human primates: steroidogenesis, endometrial development, ovulation, menstrual patterns and gamete morphology. Hum Reprod 17[3], 612-619. 2002.
5. Snow M, Cox SL, Jenkin G, Trounson A, Shaw J. Generation of live young from xenografted mouse ovaries [In Process Citation]. Science 2002 Sep 27;297[5590], 2227. 2002. 
6. Wolvekamp MC, Cleary ML, Cox SL, Shaw JM, Jenkin G, Trounson AO. Follicular development in cryopreserved Common Wombat ovarian tissue xenografted to Nude rats. Anim Reprod Sci 65[1-2], 135-147. 2001. 
7. Liu J, Van der EJ, Van den BR, Dhont M. Live offspring by in vitro fertilization of oocytes from cryopreserved primordial mouse follicles after sequential in vivo transplantation and in vitro maturation. Biol Reprod 64[1], 171-178. 2001. 
8. Kim SS, Battaglia DE, Soules MR. The future of human ovarian cryopreservation and transplantation: fertility and beyond. Fertil Steril 75[6], 1049-1056. 2001. 
9. Gook DA, McCully BA, Edgar DH, McBain JC. Development of antral follicles in human cryopreserved ovarian tissue following xenografting. Hum Reprod 2001 Mar;16[3], 417-422. 2001.
10. Callejo J, Salvador C, Miralles A, Vilaseca S, Lailla JM, Balasch J. Long-term ovarian function evaluation after autografting by implantation with fresh and frozen-thawed human ovarian tissue. J Clin Endocrinol Metab 86[9], 4489-4494. 2001. 
11. Metcalfe SS, Shaw JM, Gunn IM. Xenografting of canine ovarian tissue to ovariectomized severe combined immunodeficient (SCID) mice. J Reprod Fertil Suppl 2001;57, 323-329. 2001. 
12. Radford JA, Lieberman BA, Brison DR, Smith AR, Critchlow JD, Russell SA, Watson AJ, Clayton JA, Harris M, Gosden RG, Shalet SM. Orthotopic reimplantation of cryopreserved ovarian cortical strips after high-dose chemotherapy for Hodgkin's lymphoma. Lancet 357[9263], 1172-1175. 2001. 
13. Kagabu S, Umezu M. Transplantation of cryopreserved mouse, Chinese hamster, rabbit, Japanese monkey and rat ovaries into rat recipients. Exp Anim 49[1], 17-21. 2000. 
14. Cox S, Shaw J, Jenkin G. Follicular development in transplanted fetal and neonatal mouse ovaries is influenced by the gonadal status of the adult recipient. Fertil Steril 74[2], 366-371. 2000. 
15. Nisolle M, Casanas-Roux F, Qu J, Motta P, Donnez J. Histologic and ultrastructural evaluation of fresh and frozen-thawed human ovarian xenografts in nude mice. Fertil Steril 2000 Jul;74[1], 122-129. 2000. 
16. Oktay K, Newton H, Gosden RG. Transplantation of cryopreserved human ovarian tissue results in follicle growth initiation in SCID mice. Fertil Steril 73[3], 599-603. 2000.
17. Candy CJ, Wood MJ, Whittingham DG. Restoration of a normal reproductive lifespan after grafting of cryopreserved mouse ovaries. Hum Reprod 15[6], 1300-1304. 2000.
18. Imthurn B, Cox SL, Jenkin G, Trounson AO, Shaw JM. Gonadotrophin administration can benefit ovarian tissue grafted to the body wall: implications for human ovarian grafting. Mol Cell Endocrinol 163[1-2], 141-146. 2000. 
19. Shaw JM, Cox SL, Trounson AO, Jenkin G. Evaluation of the long-term function of cryopreserved ovarian grafts in the mouse, implications for human applications. Mol Cell Endocrinol 161[1-2], 103-110. 2000. 
20. Weissman A, Gotlieb L, Colgan T, Jurisicova A, Greenblatt EM, Casper RF. Preliminary experience with subcutaneous human ovarian cortex transplantation in the NOD-SCID mouse. Biol Reprod 60[6], 1462-1467. 1999. 
21. Baird DT, Webb R, Campbell BK, Harkness LM, Gosden RG. Long-term ovarian function in sheep after ovariectomy and transplantation of autografts stored at -196 C. Endocrinology 140[1], 462-471. 1999. 
22. Callejo J, Jauregui MT, Valls C, Fernandez ME, Cabre S, Lailla JM. Heterotopic ovarian transplantation without vascular pedicle in syngeneic Lewis rats: six-month control of estradiol and follicle-stimulating hormone concentrations after intraperitoneal and subcutaneous implants. Fertil Steril 72[3], 513-517. 1999. 
23. Meirow D, Fasouliotis SJ, Nugent D, Schenker JG, Gosden RG, Rutherford AJ. A laparoscopic technique for obtaining ovarian cortical biopsy specimens for fertility conservation in patients with cancer. Fertil Steril 71[5], 948-951. 1999. 
24. Salle B, Lornage J, Demirci B, Vaudoyer F, Poirel MT, Franck M, Rudigoz RC, Guerin JF. Restoration of ovarian steroid secretion and histologic assessment after freezing, thawing, and autograft of a hemi-ovary in sheep. Fertil Steril 72[2], 366-370. 1999. 
25. Aubard Y, Piver P, Cogni Y, Fermeaux V, Poulin N, Driancourt MA. Orthotopic and heterotopic autografts of frozen-thawed ovarian cortex in sheep. Hum Reprod 1999 Aug;14[8], 2149-2154. 1999. 
26. Gunasena KT, Lakey JR, Villines PM, Bush M, Raath C, Critser ES, McGann LE, Critser JK. Antral follicles develop in xenografted cryopreserved African elephant (Loxodonta africana) ovarian tissue. Anim Reprod Sci 53[1-4], 265-275. 1998. 
27. Sztein J, Sweet H, Farley J, Mobraaten L. Cryopreservation and orthotopic transplantation of mouse ovaries: new approach in gamete banking. Biol Reprod 58[4], 1071-1074. 1998.
28. Oktay K, Newton H, Mullan J, Gosden RG. Development of human primordial follicles to antral stages in SCID/hpg mice stimulated with follicle stimulating hormone. Hum Reprod 13[5], 1133-1138. 1998. 
29. Gunasena KT, Lakey JR, Villines PM, Critser ES, Critser JK. Allogeneic and xenogeneic transplantation of cryopreserved ovarian tissue to athymic mice. Biol Reprod 57[2], 226-231. 1997. 
30. Opsahl MS, Fugger EF, Sherins RJ, Schulman JD. Preservation of reproductive function before therapy for cancer: new options involving sperm and ovary cryopreservation. Cancer J Sci Am 3[4], 189-191. 1997. 
31. Marconi G, Quintana R, Rueda-Leverone NG, Vighi S. Accidental ovarian autograft after a laparoscopic surgery: case report. Fertil Steril 68[2], 364-366. 1997. 
32. Oktay K, Nugent D, Newton H, Salha O, Chatterjee P, Gosden RG. Isolation and characterization of primordial follicles from fresh and cryopreserved human ovarian tissue. Fertil Steril 67[3], 481-486. 1997. 
33. Gunasena KT, Villines PM, Critser ES, Critser JK. Live births after autologous transplant of cryopreserved mouse ovaries. Hum Reprod 1997 Jan;12[1], 101-106. 1997. 
34. Nugent D, Meirow D, Brook PF, Aubard Y, Gosden RG. Transplantation in reproductive medicine: previous experience, present knowledge and future prospects. Hum Reprod Update 3[3], 267-280. 1997. 
35. Newton H, Aubard Y, Rutherford A, Sharma V, Gosden R. Low temperature storage and grafting of human ovarian tissue. Hum Reprod 11[7], 1487-1491. 1996. 
36. Shaw JM, Bowles J, Koopman P, Wood EC, Trounson AO. Fresh and cryopreserved ovarian tissue samples from donors with lymphoma transmit the cancer to graft recipients. Hum Reprod 11[8], 1668-1673. 1996. 
37. Melica F, Chiodi S, Cristoforoni PM, Ravera GB. Reductive surgery and ovarian function in the human--can reductive ovarian surgery in reproductive age negatively influence fertility and age at onset of menopause? Int J Fertil Menopausal Stud 40[2], 79-85. 1995. 
38. Gosden RG, Faddy MJ. Ovarian aging, follicular depletion, and steroidogenesis. Exp Gerontol 29[3-4], 265-274. 1994. 
39. Faddy MJ, Gosden RG, Gougeon A, Richardson SJ, Nelson JF. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod 7[10], 1342-1346. 1992. 

 

 

 

Egg Freezing 2010 A Practical Update on the State of the Art by Carlene Elsner, M.D.

Egg Freezing 2010 A Practical Update on the State of the Art

by Carlene Elsner, MD

 

 

Background                         

Interest in freezing and storing gametes (sperm and eggs) for later use is nothing new. By the 1960’s the technology to freeze sperm was reliable enough, in terms of freeze thaw survival rates, to make the development of sperm banks reasonable for long term storage of donor sperm to be used by couples who needed donor sperm to conceive, and also for sperm storage for men before treatment for certain cancers, where treatment would render them infertile. Banking of sperm makes it possible to quarantine sperm for months before use, allowing for retesting of donors for sexually transmitted disease prior to thawing and use of the specimen. Initially, the per cycle pregnancy rates for the use of fresh sperm in insemination cycles were better than in cycles when frozen sperm was used. By the 1980’s sperm freezing techniques had improved such that pregnancy rates using fresh or frozen sperm were very much the same. At that time the use of frozen banked sperm began to replace the use of fresh sperm for insemination because of the increased margin of safety with its use. At the present we take the use of frozen banked sperm for granted as the state of the art when donor sperm is needed.

Until 1978 with the birth of the first IVF baby, Louise Brown, human eggs were not available to researchers in the laboratory at all for study. The first possibility to consider egg freezing did not come until controlled ovarian hyperstimulation for IVF became commonplace and there were extra eggs available that could either be inseminated to create extra embryos that could then be frozen for later use or could be frozen as eggs. It soon became apparent that with techniques available at the time, freezing embryos worked much better than freezing eggs.

Freezing sperm and freezing eggs are totally different in terms of degree of difficulty so the technology for freezing eggs did not develop as rapidly as it did for freezing sperm. The human egg is physically much larger than a sperm. The sperm is small and compact consisting largely of DNA. The larger egg contains DNA in its nucleus, but also in its cytoplasm it contains a large number and variety of intracellular organelles that are necessary for cell viability and protein synthesis. Very importantly, as opposed to the sperm, the cytoplasm of the egg largely consists of water. During early attempts at egg freezing, the slow freeze techniques in use at that time resulted in the formation of ice crystals in the cytoplasm of the egg. These ice crystals damaged the intracellular organelles resulting in frequent cell death, so freeze thaw survival rates for frozen eggs were poor. Even if the egg did not die, the spindle in the egg is particularly sensitive to damage from intracellular ice crystal formation. Damage to the spindle of the egg causes uneven sorting of chromosomes during cell division resulting in aneuploidy (abnormal embryos). The embryos derived from frozen eggs at that time were poorer in quality than embryos derived from fresh eggs. With continued work, freezing techniques improved so that by the late 1990’s pregnancy could be achieved in the human using previously frozen eggs. We, at RBA reported in 1997 two of the first successful births in the world of children derived from the use of frozen thawed eggs. At that time egg freezing was an inefficient process. It took about 100 eggs to achieve a successful pregnancy, so the technology was not practical for common usage.

More recently, with expanded use of IVF throughout the world for treatment of infertility, many governments have enacted laws limiting or prohibiting the use of certain techniques in their respective countries. These laws vary from country to country. For instance, many countries limit the number of embryos that can be transferred, Germany forbids PGD (the chromosomal testing of embryos prior to transfer), and in Italy, freezing embryos is forbidden, only three eggs may be inseminated because all embryos produced must be transferred and cannot be frozen. In Italy if a woman produces a large number of eggs still only three can be inseminated, therefore the excess eggs must be discarded, donated to another woman, or used for research. Many of these eggs in Italy have been used to improve egg freezing using the slow freeze method. In the late 1990’s almost simultaneously, a few reports of successful egg freezing from vitrification in Asia began to appear in the literature. 

 

 

Egg Freezing Technology

As of 2009, when eggs are frozen one of these two techniques are used; either the slow freeze rapid thaw method popularized in Europe or the vitrification method first used in Asia. Only mature eggs (MII oocytes) may be frozen. The slow freeze rapid thaw method is more time consuming but less difficult technically and requires less equipment in the laboratory than does the vitrification method. What this means from a practical standpoint is that centers with relatively little experience with egg freezing can have success using the slow freeze rapid thaw method. Vitrification is much less forgiving, meaning that even minor deviations from protocol can have disastrous results. Not surprisingly, most of the centers in the world that currently offer egg freezing are using the slow freeze rapid thaw technique.

In the slow freeze method, the eggs to be frozen are placed in a media containing a cryoprotectant. The concentration of the cryoprotectant is gradually increased in a stepwise fashion to draw water out of the cell to prevent ice crystal formation in the cytoplasm of the egg as the temperature is gradually lowered to freeze the eggs. Vitrification involves flash freezing of eggs where the temperature is lowered so rapidly that a glass is formed because there is no time for ice crystals to form in the freezing process. This formation of a glass does not damage the intracellular organelles in the cytoplasm of the egg like ice crystal formation does if it occurs in the slow freeze method. In labs experienced in the use of vitrification, freeze thaw survival rates of eggs as well as post thaw egg and embryo quality, per embryo implantation rates, and ongoing pregnancy rates are better with vitrified eggs than with slow frozen eggs. At the moment only a few labs in the United States routinely use vitrification for eggs freezing.

 

Results

When the ongoing pregnancy rates from the use of previously frozen eggs began to approach the success rates from the use of frozen embryos, we at RBA felt that egg freezing deserved further evaluation. We did a study to compare outcomes with vitrification and slow freezing in 2006. Briefly, we froze eggs obtained from 10 young donors. Twenty couples needing donor egg received free cycles in which some eggs were thawed for each couple and inseminated using ICSI. The average fertilization rate was 87%. Early embryo development was observed in the laboratory and 2 to 3 embryos were transferred on day 5. Fifteen of the 20 women were pregnant from the initial transfer. Of the 5 not pregnant, some had extra embryos frozen that had been derived from frozen eggs. Two women returned for thaw and replacement of these extra embryos. Both conceived, so a total of 17 of the 20 women became pregnant from egg freezing. These women delivered 28 children, all of which were healthy. These data were reported at the ASRM in Washington, DC in October 2007 (full article F&S Aug 2009).

These results were so encouraging to us that we began routinely freezing and banking eggs from donors. We opened an egg bank in December 2007. Results from the use of previously frozen eggs continue to exceed expectations. As of December 2009, we have had more that 100 babies born and there are many ongoing pregnancies. Ongoing pregnancy rates continue to be 65% or higher. Most of the women who come to us for donor egg are now preferring to use the egg bank for several reasons; 1) it reduces the price of egg donation by approximately 50%, 2) there is no wait time (over 1000 eggs from more than 70 donors are available at this writing, with constant turnover, meaning more become availably every week), 3) the intended parents can choose their own donor from the website with complete profiles and baby pictures of the donors, and 4) the results are as good as if fresh donor eggs were used.

 

Other uses of egg freezing

After the initial successes from the egg bank, we began to evaluate egg freezing in women older than those in our donor pool (21-30 years of age). Although the numbers are still small, it appears that ongoing pregnancy rates using frozen eggs are age appropriate; that is that pregnancy rates are similar for women using their own frozen eggs to the rates they could expect if they used their own fresh eggs. With vitrification, the freeze thaw process does not seem to damage the egg. This fact allows us to extend the use of egg freezing to other groups including 1) women who desire fertility preservation if ovarian reserve is good, 2) prior to treatment for women who require sterilizing surgery, radiation or chemotherapy for cancer, 3) women who require IVF for infertility treatment but do not wish to create a large number of embryos to freeze that may be potentially unused.

 

The future

The recent improvements in egg freezing hold great promise for the future. It has the potential to revolutionize family planning in much the same way as the birth control pill did in the last century. Imagine being able to plan the perfect time to have a child without having to worry about the reproductive time bomb of advancing age.

Dr. Elsner also wrote an earlier article on egg freezing in 2003.

 

 

Carlene W. Elsner, M.D. has worked in the field of infertility for over 20 years. She was the first board certified reproductive endocrinologist in Atlanta and joined Drs. Kort and Massey at RBA in 1984. Before coming to Atlanta Dr. Elsner was on faculty at Bowman Gray School of Medicine at Wake Forest University. She completed fellowships in reproductive biology at the University of Pennsylvania and in reproductive endocrinology at the Harbor UCLA Medical Center. A Georgia native, Dr. Elsner received her MD from the Medical College of Georgia. She completed a four year residency in obstetrics and gynecology at the University of Florida. 

Dr. Elsner is an INCIID Professional Member. Read her biography here.

 

Reproductive Biology Associates
1150 Lake Hearn Dr. Suite 400
Atlanta, GA 30342
Phone: 404-250-6848
Fax: 404-256-6999

 

Hormones and Endocrine Disrupting Chemicals: Low-­-Dose Effects and Nonmonotonic Dose Responses: A review by Pete Myers

Hormones and Endocrine Disrupting Chemicals: 

Low-­-Dose Effects and Nonmonotonic Dose Responses

This FAQ by Pete Myers

 

1.   What are the main findings of this paper? 
For years, scientists have looked at single chemicals and asked whether they have effects at low doses, in the range of what humans typically experience. That single-­-chemical 
approach has produced a huge amount of data, but little analysis has been done to make conclusions on a wider scale. We approached this huge body of literature and asked whether there was sufficient evidence to conclude that many or most hormone-­-mimicking chemicals have effects at low doses. We compiled examples of 30 endocrine-­-disrupting chemicals  (EDCs) that have been shown to cause low dose effects—effects very different than those at high doses.   
 

We wanted use take this broad perspective to address whether current regulatory practices for determining chemical safety were sufficient to protect human health. We found overwhelming evidence that low doses of chemicals are not safe for humans or wildlife. The failure of traditional testing methods to detect low dose responses has large implications for chemical regulation. It means that many chemical safety standards will have to be strengthened substantially to protect public health.

 

2.   What are “low dose effects?

Usually, “low dose” refers to doses that are similar to what humans experience in their regular lives, meaning a dose that is environmentally relevant. When scientists look at whether exposure to a chemical is “safe” or not, what we are really asking is whether exposure to that chemical has an effect in the environmentally relevant range. “Low dose” can also refer to the amount of a hormonally active or endocrine disrupting chemical (EDC) that has to be given to an animal to produce the same amount of chemical in blood levels that 
is similar to human blood levels of that chemical. 
 
But sometimes we have no idea how much of a chemical humans are exposed to, or how much EDC must be given to produce human blood levels. In this case, we consider “low doses” to be any dose below the doses that regulatory agencies have tested. 
 
Low dose “effects” – or the impact/consequence of exposure to an EDC at a “low dose” -­--­- include a huge range of biological changes including increased cancer incidence, altered development of the reproductive tract, abnormal brain development and behaviors, impaired metabolic responses related to diabetes and obesity, and many others.

 

3.   The study concludes that high dose tests can’t be relied upon to reveal low dose effects. Why?

Hormones, and chemicals that behave like hormones, can cause very different effects at low doses compared to high doses. We show many examples of this in the review. One clear example involves the cancer-­-fighting synthetic hormone tamoxifen, commonly used to treat breast cancer. At high doses it stops the growth of breast tumors. But at low doses it actually causes breast tumors to grow. Traditional testing methods used to test for chemical safety would completely miss this low dose effect.

The paper presents many examples where low dose effects cannot be predicted from high dose testing, and it reviews extensive information now available about the biological mechanisms that can cause this pattern. The paper concludes that this should be expected for any chemical that behaves like a hormone. The failure of traditional testing methods to detect low dose responses has large implications for chemical regulation. It means that many chemical safety standards will have to be strengthened substantially to protect public health.

 

4.   Why are these effects not predicted in the toxicology studies performed to determine the safety of chemicals on the market?

Under current FDA testing procedures, when toxicology studies are performed, very high doses of a chemical are given to animals. The animals are then examined to see if they die or have other, very obvious and serious health effects. These tests do not focus on the kinds of developmental effects that you would see if, for example, you gave an animal birth control pills or another chemical that disrupts hormones. Hormones don’t kill animals, unless they are given at extremely high doses. But they do a lot of other things to animals, and those are the endpoints that are often ignored in toxicology testing.

The traditional way of thinking about chemicals is that ‘the dose makes the poison’, or that more of a chemical produces more damage. Toxicology tests use very high doses, and then predict that a much lower dose of the chemical would be safe. But the lower dose – the “safe” dose – is never actually tested for safety. So when humans are exposed to low doses of a chemical, regulatory agencies almost never have any data to predict what types of biological effects can be expected. They don’t know, because no tests have been performed that would tell them. But we do see the effects of low dose exposures in prevalent human health problems like learning disabilities, infertility, and a variety of cancers.

 

5.   What evidence do we have that low dose exposure to EDCs adversely affects human health?

The first line of evidence we have comes from animal testing, which is the standard for determining the safety of any chemical exposure. Critics often say: “But animals aren’t people!” While this is true, the endocrine systems of animals and humans are remarkably similar. This means that the effects of EDCs, especially chemicals that act like hormone mimics, are expected to be very similar in animals and humans. And in fact, there are several examples in which animal studies predicted exactly the kinds of effects from EDCs that were later seen in exposed humans. A study of DES, the drug infamously given to pregnant women to prevent complications prior to 1970, predicted the harmful effects of this drug on the mammary gland 25 years before the daughters of those who took it were old enough to develop breast cancer.

We compiled examples of 30 EDCs that have been shown to cause low dose effects in animals. That means that low doses of these chemicals affect a range of endpoints including development of sex differences in the brain, behavioral changes, development of the male and female reproductive tracts, hormone levels in the body, bone health, obesity, and fertility, among other impacts. The second line of evidence comes from human epidemiology studies. In these studies, people that are exposed to a chemical can be compared to people that are not exposed to a chemical, and these studies indicate that EDC exposures affect human health. Additional epidemiology studies compare the amount that people are exposed to an EDC, and find that the level of exposure matters, too. In human studies, the kinds of effects associated with EDC exposures include fertility, cardiovascular disease, obesity, arthritis, bone health, endometriosis, high blood pressure, and metabolic syndrome, including type 2 diabetes.

 

6.   What kind of changes do we need to make in chemical testing to ensure the protection of human health?

Toxicology testing needs to be done so that rather than only testing high doses and guessing about which doses are safe, actual doses in the range of real life human exposures are tested for safety.

                                                        
1 Soto AM, Vandenberg LN, Maffini MV, Sonnenschein C.2008. Does breast cancer start in the womb? 
Basic Clin Pharmacol Toxicol 102 (2): 125-­-33.

Furthermore, toxicology testing needs to change its focus from asking only whether chemicals kill people or cause birth defects, to also addressing whether sensitive endpoints relevant to endocrine health, like development of the brain and sex-­-specific behaviors, or control of insulin and blood sugar levels, are affected. There are many, many academic labs doing these kinds of tests; however, regulatory agencies often ignore these data.

 

7.   If these chemicals are so pervasive, is it feasible to try to eliminate all human exposures?

EDCs are routinely used on crops (and therefore found on/in our foods), to package foods, on our lawns, in our houses, and on our bodies (soap) and clothes (detergents). They are everywhere. We are not suggesting that every single one of these chemicals needs to disappear today, but we are suggesting that they should not be considered ‘safe’. Can they be phased out and replaced with chemicals that do not have hormonal activity? Can we change the way new chemicals are tested to avoid this problem in the future? These are all questions that need to be answered.

 

8.   What are the cumulative effects of these exposures?

“Cumulative” can be interpreted in two ways. If by cumulative you mean the effects over time of exposures, the answer is complex. At different times in life, we are differently sensitive to 
chemicals including hormones. Early developmental periods (fetal, neonatal and infant periods) are incredibly sensitive to EDCs and hormones. Exposures to hormone mimics (or hormone blockers) in the womb will have permanent effects because hormone-­-induced changes during this sensitive period will alter development of organs in ways that can never be reversed. Puberty is also a sensitive period. We often think of adult EDC exposures as less harmful, but that might not be true. More and more human studies show links between adult exposures and diseases or dysfunctions such as infertility, cardiovascular disease, type 2 diabetes and obesity. There may also be sensitive periods late in life, i.e. elderly adults may have a heightened sensitivity to hormones. And EDCs may interfere with treatment for some cancers. If by cumulative you mean the effects of multiple chemicals, this is a very important issue that needs a lot more attention. Some studies show that when low doses of chemicals are mixed together, they have effects that could not be predicted from the effects of single chemicals alone. Humans are exposed to mixtures of chemicals – dozens if not hundreds every day. Knowing how these chemicals interact with each other, as well as their interactions with natural hormones, is an important research need. We do not yet have the answer to this question, but it’s one we should not ignore.

 

9.   In those cases where low doses are associated with worse effects than high doses, doesn’t a greater amount of exposure effectively eliminate the threat?

This is a common misunderstanding. It is not that these chemicals do not cause harm at high doses – they cause very different effects at high doses. High dose toxicology studies show that these chemicals can be deadly, or block pregnancies, or induce birth defects at high doses. These incredibly visible effects are not seen at low doses, which is why some think they are safe at low doses. But at low doses, they affect a wide range of other endpoints. The other important thing to keep in mind is that our bodies are not a single cell type or a single organ. Let’s say that you could identify a dose of an EDC that does not induce mammary cancer. That doesn’t tell you anything about whether that dose is ‘safe’ – because a dose that doesn’t affect the mammary gland could affect the brain, or fertility, or metabolism. 

 

10. If we are being harmed by low-­-dose exposure to EDCs, what can we do to protect ourselves?

Because this isn’t a single chemical issue, it is not easy to make suggestions to consumers. If this were a question of how to avoid a chemical applied to your lawn to control grubs, the answer would be “don’t use it.” But so many of these chemicals are contaminants in our foods, are in the air and water, and are in consumer products that aren’t labeled. Instead, this study suggests that we need to change how we think about chemical safety, and start to deal with the hundreds (or thousands) of chemicals on the market that are EDCs.
The real point of this paper is to show that this isn’t a single chemical issue. Low dose effects are observed for dozens of widely-­-used chemicals. We propose that scientists and regulators should expect EDCs to have effects at low doses and to test for them explicitly. That is not done today and it means many safety standards for chemical exposure are too weak.

 

Just published is a  huge review of low dose and non-monotonic effects in Endocrine Reviews, with Laura Vandenberg as first author. Nothing like it has ever been done.

Review: http://bit.ly/A25AWs

Birnbaum's editorial: http://bit.ly/y2RAl0

Cone's story: http://bit.ly/x4bGYO

Vandenberg's op-ed: http://bit.ly/yzjnqK

Don't miss, in the review, an evaluation of how 'weight of the evidence' risk assessments must be done for EDCs using endocrinological principles, and what that means for bisphenol A.
Bottom line of the review: Non-monotonicity is common and should be the default expectation for endocrine disrupting chemicals. This means a large number of current safety standards are too weak.

TURNING BACK THE REPRODUCTIVE CLOCK: New Science, Old Wisdom By Randine Lewis MSOM, L.Ac., Ph.D.

Regarding the human egg: How old is too old? Perhaps we are asking the wrong question. Remember the psychological argument about nature vs. nurture? Let’s rephrase the topic altogether.  How can we help women in their mature reproductive years produce healthy children? I propose that the answer is found in the nature vs. nurture discussion. Nurturing the follicle in the 120 days before ovulation  will produce a healthy egg, free of transmutation, free of the need for medical intervention.
 
Scientists have told us that in about 45 years all the eggs that we’re born with will have deteriorated. Yet, the latest evidence is challenging our previous doctrine. Now, they pronounce, mammalian ovaries may have specialized stem cells that make new eggs throughout the female’s life. And this could, they say, lead to powerful new treatments for infertility. Women who heretofore have been told that their eggs are “too old” to become babies, are renewed with hope, just as they were when cytoplasmic transfer was a promising solution a few years ago. Yet, as scientists and politicians snatched that possibility away from us, we were left once again with the hopeless pronouncement that old eggs have a dismal possibility of propagating. Letting a youthful woman donate her fresh, perfect eggs to replace our shriveled, dieing ones has been the only answer for women with “poor quality” eggs.  Poor quality eggs mean the ones that won’t act in response to Western medicine’s attempt to force a pregnancy in a reproductive system that seems resistance to artificial hormonal stimulation. They call us “poor responders”, “clomid failures”, or “IVF failures”.
 
I have been treating poor responders, older women with high FSH, those with premature ovarian failure, poor quality eggs, and yes, even those dismal “IVF failures” for years. Yet because of their successful response, I no longer believe the dogma that our eggs deteriorate, that they go bad, or that we are failures. I believe Western reproductive medicine sometimes fails us. Why? Because when I have been able to embrace a woman whose only desire in life is to become a mother, using the ancient wisdom of Chinese medicine, within a few months of gentle ovarian balancing therapy, her body responds. Her ovaries seem to wake up in reply, somehow liberating “healthy” eggs.
 
In an effort to understand what this process really was, I had to shift my own paradigm. After completing my medical school academics, I too was told I was infertile. Barren was the word that came to mind, and panic set in. I could tell that this terror was worsening my already bleak diagnosis. But, fortunately, I held a kernel of disbelief within that wouldn’t accept my doctor’s pronouncement. By this time I had enough medical knowledge to realize that since the endocrine system worked via feedback, that taking external hormones may force ovulation, but wouldn’t resolve the underlying disorder. After all, if my ovaries weren’t producing the right hormones, how could they be producing healthy eggs?! That’s what I had to find out on my own. And somehow I knew deep inside that the answer was natural and healthy, if I could just find it.
 
Let me explain what I have come to know about the amazing female reproductive system. First of all, it is perfectly created. The biology of the ovary itself is remarkably intelligent and interactive with the rest of the body. It is, after all, the source of all human life on this planet. Our body knows how to protect it, too. If a little boy gets mumps or a high fever, he may become permanently sterile. Not so a little girl. Her ovaries, although deep within her body, are protected from their surroundings before the process of meiosis is initiated.
 
This may make her ovaries temporarily unresponsive, but as her eggs are protected, so are they innately fruitful and responsive when the conditions are right. We have just been viewing them through scientific lenses which have no vision for what our role can be, not through the lenses of our deep, internal sense of knowing we have more potential than we are ever given credit.

 
“If we remain obsessed with seeds and eggs,
we are married to the fertile reproductive valley of the Mysterious Mother,
but not to her immeasurable heart
and all-knowing mind.”
 
Hua Hu Ching

 
Let’s look at the immeasurable heart and all-knowing mind of the Mysterious Mother, that which is capable of bringing life into being. Take off the glasses of the scientific “truths” you have been commanded to believe, and put on your glasses which allow you to see from that internal place where our intuitive wisdom resides.
 
Whether we have a million egg cells or continually regenerating germ cells really isn’t the issue. What happens to the follicle, the egg’s miniature dwelling, as it’s cycling through its many phases of receptivity is extremely important to the health and future quality of its residing egg. Look at the following diagrammatic representation of the process within the human ovary at every reproductive stage. Puberty initiates this process, which continues until about age 52, the average age of menopause in the U.S.
  
Each follicle remains mere potential until it reaches its growth phase. Only NOW will its outcome be determined. Our multitudes of elemental follicles, in their initial dormant state, have not yet begun the phase of division. Then, by some mysterious ongoing signal, which even reproductive science doesn’t understand, hundreds of follicles are awakened from their primordial state of rest, about five months before one will be selected for ovulation. At this stage, they remain in a state of biologic perfection, until they begin to interact with their environment. Let’s follow one active follicle and its residing egg through this miraculous process of folliculogenesis.
 
About four months before this particular egg’s domain is selected to be the lucky ovulatory one, a chamber of fluid appears within the follicle. The follicle quadruples in size, and undergoes many stages of proliferation as the fluid filled chamber expands. Now hormone regulating factors within the ovary itself (which is responding to our own internal environment) start to influence the contents of the follicular fluid.  The ovary’s messages to the follicle, which are affected by blood flow, nourishment, and hormonal cues within the body, influence the state of the follicular fluid. Regulatory proteins, hormones and growth factors begin to appear about the time the egg starts to undergo division. In a perfect, non-stressed milieu, the messages will be clear, and the egg will be healthy. However, if any of three factors are substandard, the health of the egg will reflect the state of the rest of the body:

1)       If nourishment is poor,
2)       if the hormonal cues have been interrupted, or
3)       if the blood flow has been compromised.

The egg’s health is determined during the growth phase, when protein synthesis occurs - after the egg has starts to communicate and become responsive to hormonal and environmental factors:  3 months before it is released. This is what determines egg quality!
 
If blood flow to the ovary has been compromised through stress or age (as we approach menopause the ovarian blood flow is around five times less than when we were in our reproductive prime), the follicular fluid will contain rising levels of vascular endothelial growth factor, the same chemical found in a damaged heart muscle, which signals the body that the organ is asphyxiating and needs more blood flow.

Further, poor diet begins to show its effects the older a woman becomes. This is the time her system can become revved up with nutritional supplements.
And, as a woman ages, her hormone levels start to fluctuate. The lack of communication between the brain, the pituitary gland, and the ovaries makes the follicles resistant, and they quit paying attention to follicle stimulating hormone.
All of these changes are reflected in the follicular fluid, which will determine the health of the egg.
 

Western reproductive medicine can only manipulate the follicles during the selection phase, after the quality and health of the residing oocyte has been determined!  I knew my reproductive system was not healthy. When I was faced with my own fertility challenges, I had to find other methods to improve this scenario which had occurred inside my own body.  I found three methods that worked:
 
1) Blood flow - Fortunately, I found that certain acupuncture and acupressure techniques are known to improve blood flow to the ovaries. Better circulation to any organ improves its function, and this is especially true of the ovaries, the follicles, and their residing eggs. The femoral massage, ovarian massage, and electroacupuncture to the low back dramatically reduce the stress and age induced constriction of the uterine and ovarian blood vessels.
 
2) Nourishment - Certain dietary supplements like wheat grass, blue-green algae, and royal jelly are known to affect the nutritional state of follicular health, and therefore the state of the egg. Avoiding coffee (tea is O.K., it doesn’t release stress hormones), refined carbohydrates, and for most people – avoiding dairy and hormonally treated animal products will clear out the toxic effects of poor diet.
 
3) Hormonal balance – our delicate endocrine systems operate via feedback, meaning that the hormones won’t work appropriately unless the brain senses the right cues from our tissues. Properly prescribed herbal formulas, which address the underlying pattern of imbalance, can restore our own hormonal functioning. By stimulating the body’s own reproductive tissues at different parts of the reproductive cycle, herbal medicine is a gentler, healthier, more organic response to fertility problems. Herbal formulas are combined in sophisticated preparations which actually create greater effects than the same herbs would if taken alone. Most of the ingredients in our herbal formulas prescribed for fertility challenges have little or no direct hormonal effects, but the effect of the whole formula will substantially increase hormone levels. This synergy of different herbal combinations is at the base of many of the Chinese patented herbal formulas. These are either unaided or are employed in preparation for assisted reproductive techniques.

 
When hormone levels are balanced, and when adequate blood flow, oxygenation and nourishment are provided during the follicular growth phase, women become pregnant naturally, with their own healthy eggs, as I did with mine (it took three months). If they opt for Western reproductive methods, the likelihood of success is substantially increased. When we encourage a woman’s body to return to more youthful reproductive condition, then the ovaries produce and release eggs in the same way they did when we were younger. This assumption was confirmed in a recent scientific study where the ovaries of menopausal rats were transplanted into hormonally youthful rats’ bodies. Guess what? The ovaries resumed ovulation!
 
This isn’t a process of struggle, of swimming upstream against all odds, of “forcing” a pregnancy. You can’t force a pregnancy, I can’t force a pregnancy, and your RE can’t create a life without the cooperation of the same universal forces that our bodies respond to. Life is allowed to manifest, which is a process of acceptance. We hear examples of this universal truth all the time. When we let go of our tight hold, and loosen up our grip on the outcome, (through giving up, through adoption, through being told we’re hopeless, too old, or whatever else ends the struggle), we can finally unclench; we can lift up our hands and let go. Only then does the space open up for our reproductive energies to become receptive. Only then can Life say, “O.K., now you’re ready!”
           
Hailey was one such woman. This 44 year old desperately wanted a child, and thus went through multiple cycles of hormonal stimulation and inseminations, always to fail. Despite her doctors telling her there was no hope; she was just too old, she kept going, kept searching, not accepting “no” for an answer. She came to see me and began a regimen of dietary adjustment, acupuncture stimulation and herbal therapy. She enrolled in a mind-body wellness program for stress reduction. The last doctor she consulted told her at her age, he would only help her if she considered a donor egg in-vitro procedure, using another woman’s younger eggs. Hailey gave up her quest. Yet she continued on her regime of healthful living, as the combined methods seemed to be allowing her to accept her state of heartache better. Hailey became pregnant naturally. She gave birth to her son during her 45th year.
 
As in Hailey’s case, it is important for women of all ages to be able to empower themselves and trust their own inner wisdom. There is much that can be done to preserve, enhance, and increase our fertility at almost every stage of life. Yes, we can extend our childbearing years if needed, but we also must learn to celebrate the stages of our lives as they occur, to accept our full potential and also our limitations, and to maintain our health at its highest level no matter what our age or stage in life.

 
Dr. Lewis Moderates the INCIID Alternative Medicine Forum
 
Randine Lewis, MSOM, L.Ac., Ph.D.

Author of The Infertility Cure,

The Ancient Chinese Wellness Program for Getting Pregnant and Having Healthy Babies

WWW.FERTILITYRETREATS.COM

Webinar - Fertility Enhancement with Complementary Medicine with Randine Lewis, Ph.D.

Webinar: Enhancing your Fertility Through Complementary Medicine
January 10, 2004 11:00 AM ET

 

Featuring Dr. Randine Lewis and produced by INCIID 
Find out how complementary medicine can enhance your fertility.

Dr Lewis has spent her professional career helping other women conceive. She applies her knowledge and training in Western, Eastern, and Alternative medicine to address natural treatments of infertility.

 

She recently authored THE INFERTILITY CURE, THE ANCIENT CHINESE WELLNESS PROGRAM FOR GETTING PREGNANT AND HAVING HEALTHY BABIES - "A wonderfully authoritative answer to the collective prayers of the many thousands of women who want to have a baby but have been told that they're "infertile." Using the considerable wisdom of Traditional Chinese Medicine, Dr. Randine Lewis lays out an ancient but fully updated way to preserve and enhance your fertility." - Christiane Northrup, M.D., author of Women's Bodies, Women's Wisdom

 

Dr. Lewis founded Eastern Harmony Clinic in Houston, Texas, and presently offers fertility enhancing retreats in Asheville, North Carolina and Tucson, Artizona. 
She is the co-moderator for INCIID's Complementary Medicine Forum.
If you have any problems with this audio visual presentation, please contact us here: alert@inciid.org

SEE the Video Web Cast with Geoff Sher, MD: New Breakthrough in IVF. Study Doubles IVF Success

NEW STUDY --- Doubles the IVF Success Rates -- Geoffrey Sher will be coming to INCIID to chat about this breakthrough
You will need Windows Media Player to view this audio/video webcast.
Download the free media player here.

 

(SEE THE VIDEO OF THE WEBCAST  ---- CLICK HERE)

A process that could markedly improve pregnancy rates from In Vitro-Fertilization (IVF) was reported in a
study published in the prestigious medical journal Fertility and Sterility (F&S). 
This was presented on Feb. 15, 2007 - 9:30 PM ET

 

      "This very exciting breakthrough could more than double IVF pregnancy success rates while reducing the risk of multiple births. We are now much closer to the goal of one IVF attempt, one egg, and one embryo, yielding one healthy baby," said Dr. Geoffrey Sher, who along with Levent Keskintepe PhD , both of ReproCure, LLC and the Sher Institutes for Reproductive Medicine(SM) (SIRM) developed the process and conducted the study.

Dr. Geoffrey Sher will come back to INCIID and do a follow up chat with us. TBA  

Start sending your questions ahead of time, please email them "WebCast" using the INCIID Contact Form
Subject of your email should be IVF Breakthrough Question
Check back here for time and date of this chat.