If you take the time to read this website you will see why Cooper Institute for Reproductive Hormonal Disorders is your best choice for an infertility center.  Even if you do not select us after reading our website you will know a lot more about infertility and its therapy and diagnosis.

 INTRODUCTION

             Welcome to the Cooper Institute for Reproductive Hormonal Disorders.  This medical practice is dedicated to helping women who are having difficulty with infertility or miscarriage to have live healthy babies.  In addition the practice treats women having gynecologic problems especially related to hormonal disorders including lack of menstruation, excessive menstruation, excess facial and body hair, hair loss, pelvic pain and severe cramps.  The practice also treats males with subnormal semen specimens using non-surgical approaches.  However, urologic surgeons are available if needed.  Furthermore the practice will treat medical endocrine problems, e.g., disorders of the thyroid, adrenal, and pituitary but does not treat diabetes.

 History of Cooper Institute:

             The founder of Cooper Institute is Jerome H. Check, M.D., Ph.D.  He completed his fellowship in Reproductive Endocrinology and Infertility at Thomas Jefferson University in 1977 and became Board Certified in Endocrinology and Metabolism.  He stayed at Jefferson and maintained a dual appointment in Obstetrics and Gynecology and Internal Medicine and eventually became an associate professor of OB/GYN and an assistant professor of medicine.

             After remaining at Thomas Jefferson University for 17 years he was asked to become a professor of OB/GYN at Robert Wood Johnson Medical School, Camden Division and to become the division head for reproductive endocrinology and infertility, at the hospital for Robert Wood Johnson Medical School at Camden, Cooper University/Hospital to provide the medical education for the residents in OB/GYN and the medical students.

             Dr. Check who has a Ph.D. in reproductive biology (thesis title “The role of progesterone in promoting fertility and preventing miscarriage is through the stimulation of immunomodulatory proteins”) had established the first non-hospital based free-standing IVF center in the Delaware valley area in 1988 in the Philadelphia, PA area while he was still at Thomas Jefferson University.  He was asked to set up another IVF facility at Cooper Hospital and it was decided to pattern it after the PA facility.  Thus another free-standing IVF center was started in the suburban town of Marlton, NJ.  This site was chosen for easy access by turnpike and major highways.  We have been in the same location since 1991.

             To help him set up the IVF center he hired Jung K. Choe, M.D., a board certified specialist in reproductive endocrinology and infertility.  Dr. Check became the laboratory and medical director of the IVF facility and Dr. Choe became the program director.

             Besides the teaching of medical students and OB/GYN residents Dr. Check and Choe had been responsible for post-graduate training of OB/GYN residents in the field of reproductive endocrinology and infertility.  Two of these post-graduate physicians remained as associates and Drs. Deanna Brasile and Rachael Cohen have been associates for 6 years and 2 years, respectively.  Another physician Dr. Samuel Jacobs completed his fellowship in reproductive endocrinology and infertility at the same institution as Dr. Choe at the University of Connecticut School of Medicine and has worked part-time for Cooper since 1997.

             Dr. Check has recently removed himself from laboratory director of the IVF center and passed this responsibility to one of his long-term embryologists, Donna Summers- Chase.  The facility is open seven days a week and consultations can be made with any of the associates during daytime hours and can be made with Dr. Check every weekday and Tuesday, Thursday and Friday evenings.  Besides the Marlton, NJ facility consults and monitoring can be made at the PA facility which is in Melrose Park, PA (a suburb of Philadelphia) at the original site of the first IVF facility.

 What makes Cooper Institute for Reproductive Hormonal Disorders special?

 Personalized service because we really care about you

             From the moment you have your first in depth initial consultation you will see the practice of good old fashion medicine.  After an in depth taking of your history you will be provided a great degree of medical information by the doctor conducting the initial interview that will enable you to actively participate in your type of treatment and type of diagnostic tests.  Expect that first interview to be a minimum of one hour and frequently much longer.

 We understand economics and try to make the treatment affordable

             Achieving a pregnancy does not need to be expensive.  Though ultimately in vitro fertilization-embryo transfer (IVF-ET) is the quickest most effective means of achieving a pregnancy the majority of couples can achieve a pregnancy with other therapies that do not require the expensive IVF-ET procedures.  We are especially suited for finding no-IVF solutions since our head, Dr. Check, is a pioneer in the field of reproductive endocrinology and infertility and has published over 600 articles in peer reviewed journals over the last 35 years.  Many of these articles deal with unique original methods of diagnosis and treatment of infertility that has allowed us to quickly correct infertility problems despite failures in other infertility centers.  Some of these innovative ideas and methods will be discussed further in another section.

             However if IVF-ET is needed we still try to reduce costs for our patients.  When you look at the cost section you will realize that we are one of the least expensive IVF centers especially for a very successful highly experienced one.  But the approximate price of $6000.00 for egg retrieval, embryo development and embryo transfer is not the only way you save money as seen in the next section.

 Besides the initial low price for IVF-ET other ways to save you money

 1.         Our own pregnancy rates following frozen embryo transfer are about the same as when we transfer embryos fresh.  Many other IVF centers do poorly with frozen embryo transfer and make you go through the process of stimulating many eggs and oocyte retrieval if the first IVF-ET does not work.  The cost for frozen ET is about half of a fresh transfer not counting the saving on expensive drugs used for controlled ovarian hyperstimulation, blood work and ultrasound monitoring, and anesthesia.  Our success rates is related to our research since the reason why we are more successful than most other IVF centers with frozen embryo transfers is because we developed this particular freezing technique and it differs from the one used by most other IVF centers (Check JH, Choe JK, Nazari A, Fox F, Swenson K: Fresh embryo transfer is more effective than frozen ET for donor oocyte recipients but not for donors.  Hum Reprod, 16:1403-1408, 2001).

 2.         You can get IVF-ET free!  How?  Participate in our shared oocyte program (Check JH, Fox F, Choe JK, Krotec JW, Nazari A:  Sharing of oocytes from infertile versus paid donors results in similar pregnancy and implantation rates.  Fertil Steril 2004;81:703-704).  If you are willing to share half of the eggs retrieved with another woman who is either deficient in egg supply or has poor quality eggs she pays the entire price for your stimulation medication, your ultrasound and blood monitoring, and your cost of IVF-ET.  Your pay only $250.00 extra if there are extra embryos to freeze (there usually are extra embryos even despite sharing) and storing frozen embryos costs $250.00 every six months.  If you fail to get pregnant your option is to just do the affordable $2800.00 for a frozen embryo transfer or save these frozen embryos for the future and do another shared IVF-ET cycle.

 3.         If you are a donor egg recipient by choosing an infertile donor whose eggs give you the same pregnancy rate as paid donors you immediately save a lot of money because you do not have to pay the $8000.00 fee to paid donors.

             However, even you choose a paid donor you can save a lot of money by sharing these eggs with another recipient.  Not only is the fee to the donor shared but so are the costs of medications, monitoring and anesthesia and the actual oocyte retrieval (Check JH, Fox F, Deperro D, Davies E, Krotec JW:  Efficacy of sharing oocytes from compensated donors between two recipients.  Clin Exp Obst Gyn 2003;30:199-200).

             But even without these cost saving methods you will find our overall charge to the recipient receiving donor egg is half to even a third of the charge by other major experienced IVF centers like we are at Cooper.

 4.         Mild ovarian stimulation:

             Mild ovarian stimulation not only saves money on the expensive FSH injections but we charge only $3100.00 (half of the normal price for IVF-ET).  We have shown that this technique not only can produce excellent live delivered pregnancy rates in women with elevated day 3 serum follicle stimulating hormone (FSH) and decreased egg reserve (Check JH, Summers-Chase D, Yuan W, Horwath D, Wilson C:  Effect of embryo quality on pregnancy outcome following single embryo transfer in women with a diminished egg reserve.  Fertil Steril 2007 Apr;87(4): 749-56; Check JH:  Mild ovarian stimulation.  J Assist Reprod Genet 2007;24:621-627.) but this technique will provide higher pregnancy rates on the fresh transfer in women with normal oocyte reserve.  Using less drugs in women with normal egg reserve not only saves lots of money for medication and the cost of the IVF-ET but we can still create many embryos allowing some left over for future frozen embryo transfer.

 What else makes us special?

 We willingly accept the challenge of difficult cases.  We are world renown as problem solvers

for cases that have baffled other experts.

             A woman came to us for consultation from Israel.  She had six years of treatment for her obvious problem of not ovulating (she did not get menstrual periods on her own) but had everything corrected with fertility drugs, progesterone support after ovulation, and intrauterine insemination for 6 years.  She had four laparoscopies and everything was perfectly normal but she did not conceive.  She never did IVF because she could not afford it.

             Someone in the family died and she inherited a lot of money so that now she could afford IVF.  She made an appointment first with one of the foremost IVF centers in the United States but she failed to conceive after two IVF-ET cycles.  She then tried another famous IVF center in England and failed again to conceive after two more IVF-ET cycles.  She then tried one of the best IVF centers in Israel and they actually transferred back into her 12 embryos at a time!!  But she still failed to conceive after a total of six IVF-ET cycles in Israel.  Thus she had a total of 92 embryos transferred over 10 IVF-ET cycles, the equivalent of 46 failed IVF cycles if one considers transferring two at a time.

             She next came to see us at Cooper because of our reputation of solving difficult cases.  She conceived on our first IVF-ET attempt!!  What did we do different?  Well, we were aware that the fertility drugs, e.g., clomiphene citrate, menopur, bravell, gonal-F and follistim sometimes may create an adverse uterine environment even in women with normal egg reserve (i.e., normal day 3 serum FSH) (Check JH, Nowroozi K, Wu CH, Adelson HG, Lauer C:  Ovulation-inducing drugs versus progesterone therapy for infertility in patients with luteal phase defects.  Int J Fertil 1988;33:252-256).  So we purposely did not transfer fresh any of the 27 embryos but cryopreserved them all.  She conceived the first time we thawed some embryos and transferred five embryos back on day 3.  She delivered a single healthy live baby (Check JH, Choe JK, Nazari A, Summers-Chase D: Ovarian hyperstimulation can reduce uterine receptivity.  A case report.  Clin Exp Obst Gyn 27(2):89-91, 2000).

             To save the woman a trip back to the USA to have another frozen embryo transfer (we had 20 left) we suggested that she try metformin to try to induce ovulation without fertility drugs.  We advised her that some patients with polycystic ovaries (PCO) will spontaneously ovulate after a delivery.  In either case we advised the use of progesterone supplementation after ovulation.  She returned at age 40 for another frozen ET.  She did in fact have nine regular menstrual cycles starting three months after delivery.  However she forgot to take her progesterone.  We calculated that she was three days after ovulation so she would have to wait another month to transfer the frozen-thawed embryos because she was not in synchrony.  So we added progesterone.  She conceived and delivered a healthy baby (Check JH, Check ML: A case report demonstrating that follicle maturing drugs may create an adverse uterine environment even when not used for controlled ovarian hyperstimulation.  Clin Exp Obst Gyn 28:217-218, 2001).  We still have her frozen embryos to transfer some other time.

             Another woman, a physician in Belgrade, Serbia, gave up her job and took a research position in a nearby US medical school so she would be treated at our facility.  Though only in her 30’s she had marked diminished egg reserve approaching menopause.  She went to Spain for two donor egg cycles, but failed to conceive.  However, because she never achieved an endometrial thickness of greater than 4mm despite high dose estrogen replacement they told her in Spain they would not do any more donor egg cycles with her; only if she would use a gestation carrier (i.e., another woman to carry the baby).

             Because of our work in reversing menopause and making women ovulate and techniques we invented for achieving pregnancies despite marked diminished egg reserve and because of our publications on endometrial thickness and our willingness to treat women with diminished thickness (though we agree a thin endometrium does reduce the chance of pregnancy – but not impossible) she requested that we induce ovulation despite the diminished egg reserve using the mild ovarian stimulation protocol needed for achieving good pregnancy rates when women have high day 3 serum FSH.  We then performed IVF-ET with intracytoplasmic sperm injection (ICSI) (one sperm carefully injected into each egg) because of a male factor problem.

             We did not have any great tricks to offer her at that time to increase the endometrial thickness (Check JH, Graziano V, Lee G, Nazari A, Choe JK, Dietterich C:  Neither sildenafil or vaginal estradiol improves endometrial thickness in women with thin endometria after taking oral estradiol in graduating dosages.  Clin Exp Obst Gyn 2004;31:99-102) (we are investigating a new method at this time to improve endometrial thickness).  Nevertheless it is not unprecedented to achieve a pregnancy with a 4mm endometrial thickness since there has been one case report of a successful pregnancy with IVF-ET with a maximum 4mm thickness and we published a success without IVF-ET with a maximum 4mm thickness (Check JH, Dietterich C, Check ML, Katz Y:  Successful delivery despite conception with a maximal endometrial thickness of 4mm.  Clin Exp Obst Gyn 2003;30(2-3):93-4).

             We did explain the odds of success based on thickness not on diminished oocyte reserve would be low.  Nevertheless, of most importance to her was carrying and delivering a baby herself and she wanted to take a chance.  We were willing to give her that chance even though failure could lower our published pregnancy rates with IVF-ET in the Society for Assisted Reproductive Technology, i.e., SART.  We care more about people’s wants and needs than pregnancy rates!!  Actually she did not lower our pregnancy rates.  Though she failed to conceive after the first IVF-ET cycle with a 4mm endometrial thickness she was very successful on her second attempt despite a peak endometrial thickness of only 3.6mm (Check JH, Cohen R:  Live fetus following embryo transfer in a woman with diminished egg reserve whose maximal endometrial thickness was less than 4mm, Clin Exp Obst Gyn, in press).

 Understanding the comparison of SART pregnancy rates amongst different IVF-ET centers as published by the Center for Disease Control

             In vitro fertilization is frequently not paid for by third party insurance carriers and if they do they generally place a limit on the number a person is entitled to have.  Unfortunately though prices vary from IVF center to IVF center from moderately to extremely expensive no where is it actually cheap.  Unfortunately the old adage “you get what you pay for” does not necessarily apply to IVF.  Thus it is nice that a couple needing IVF can compare pregnancy rates amongst different centers and make sure their money is well spent. 

            Just as prices vary amongst IVF centers so do salaries among physicians.  The majority of physicians in various fields have to work very hard and generally make a decent living but in general the majority of physicians are not amongst the richest in society.  However, physicians should not be penalized and should have the right to become rich if they so desire.  Some medical field, e.g., pediatrics does not usually produce wealthy physicians but doctors still go into this field to help relieve suffering while still making a decent living.  Most reproductive endocrinologists will not become very wealthy but this field does have the potential for some physicians to make a lot of money.  This is because of the high prices that are generally charged.  True there is a great degree of overhead but if one can perform a lot of IVF services at very high prices there is the potential for some infertility specialists to become very wealthy.

             To attract couples to their own IVF center and not to others, with published statistics available it is imperative for that given IVF-ET center to develop a successful IVF-ET center.  Similarly, some IVF centers compete to get contracts from large corporations who provide IVF services to their employees and naturally these large companies want more “bang for their buck” and carefully evaluate the pregnancy rates of the IVF centers competing for the contracts.  Thus in an effort to show higher pregnancy rates another trick is to only take easier cases and not ones more likely to fail.  Though there is a caveat stated by SART that statistics may vary according to the type of cases seen by different IVF centers most people probably do not fully understand the statement and assume that a higher pregnancy rate by one center over another means it has a superior staff or equipment.

             One of the ways statistics are misleading involves frozen embryo transfer (Check JH:  A proposal to change the method for determining the outcome according to the SART statistics – pregnancy rate per retrieval.  J Assist Reprod Genet 2004;21:127-128).  If a woman appears to be at an increased risk of the ovarian hyperstimulation syndrome (Check JH, Wu CH, Gocial B, Adelson HG: Severe ovarian hyperstimulation syndrome from treatment with urinary follicle stimulating hormone: Two cases. Fertil Steril 43:317‑319, 1985), we have shown that embryos from women that have purposely all been frozen and fresh embryo transfer deferred (because pregnancy will markedly increase the severity of the ovarian hyperstimulation syndrome (OHSS)) will result in similar pregnancy rates as fresh embryo transfer once thawed and transferred in another cycle.  However, the way SART calculates the statistics if we purposely defer the transfer, we automatically get a zero for the pregnancy rate per retrieval.  Thus if a given IVF center has confidence in their freezing technique they may proceed with egg retrieval but purposely freeze all the embryos to avoid OHSS because pregnancy makes this condition much worse, but yet SART penalizes the cycle by giving that center a zero pregnancy rate per that retrieval (Check JH, Katsoff B, Choe JK:  Embryos from women who hyperrespond to controlled ovarian hyperstimulation do not have lower implantation potential as determined by results of frozen embryo transfer.  In:  International Proceedings of the 13^th World Congress on In Vitro Fertilization and Assisted Reproduction and Genetics, Monduzzi Editore, Pgs. 109-113, 2005).  What would be fair would be to allow the outcome of the first frozen embryo transfer to be included.  Remember those centers canceling the IVF cycle still subjected the women to time and money spent for monitoring and medication.  Some centers proceed with retrieval and embryo transfer but then subject the women to risk of OHSS.

             The body normally goes though a lot of effort to make one egg each month and there is reason to believe that this egg is usually the best one in the lot.  This is why mild ovarian stimulation works so well – it allows Mother Nature to eliminate the worst eggs and select the best one.  Nevertheless there are multiple eggs in a given group selected each month that have potential to produce normal babies.

             The hard part of IVF-ET is the need for expensive FSH drugs to stimulate multiple eggs, the need for careful monitoring by bloods and ultrasounds, and the egg retrieval process which requires anesthesia.  In contrast a frozen embryo transfer hardly requires any monitoring, and the simple embryo transfer is painless.  What many IVF centers do is to produce multiple embryos and then try to find the best one(s) in the group to transfer.  Sometimes this is at the expense of sacrificing some embryos that could have been made into babies. 

            One strategy employed by some IVF centers to increase their pregnancy rates per transfer (a statistic most people review) is to allow the embryo to develop into a ball of cells on the fifth day from fertilization.  This is known as a blastocyst.  What most infertile couples assume is that if an embryo fails to survive from day 3 (a time when we do most of our embryo transfers) to day 5 that the embryos had they been transferred on day 3 would not have resulted in a live pregnancy.  This is not true.

             Thus blastocyst transfer may result in overall a lower pregnancy rate per given egg harvest.  Interestingly, if one wants to “pad” their statistics if a woman undergoes ovarian hyperstimulation, egg retrieval and none of the embryos make it to day 5, i.e., the blastocyst stage that cycle does not have a negative impact on the statistics of that center because the woman did not have a transfer.  Thus not to be misleading there should be an adjustment made if a retrieval is performed but no embryos survive for transfer that should be counted as a failure for embryo transfer even if one was not performed.

             To illustrate this we published an article entitled “A novel method to evaluate pregnancy rates following in vitro fertilization to enable a better understanding of the true efficacy of the procedure” (Katsoff B, Check JH, Choe JK, Wilson C:  Editorial article:  A novel method to evaluate pregnancy rates following in vitro fertilization to enable a better understanding of the true efficacy of the procedure.  Clin Exp Obst Gyn 2005;32:213-216).  We showed that for women 35 and under we had a live delivered pregnancy rate per transfer of 46.9%, for women 36-39 a live delivered pregnancy rate of 36.3%, for women 40-42 23.2% and for women >43 a live delivered pregnancy rate of 20.0%.  These statistics are not bad.  But when comparing SART statistics a couple may decide to choose a center showing a live delivery rate of 62% for women 35 and younger.  The difference could be related however to our center seeing mostly difficult cases and the center with the higher statistics seeing the easy cases.

             However, if the other IVF center does not emphasize embryo freezing and tries to select the best embryo, our IVF center could provide that couple with the chance to have the most pregnancies from a given egg harvest.  For example if we look at the concept we proposed for pregnancy rate per oocyte harvest (i.e., the pregnancy rate per a given embryo retrieval following the fresh or subsequent frozen embryo transfer of embryos derived from that retrieval before having to do another egg retrieval) evaluated this way our live delivered pregnancy rates for these 4 groups were 65.0%, 45.6%, 35.2% and 25.0%.  This study eliminated women with elevated day 3 FSH levels though we will show later that with using the correct stimulation protocol high day 3 serum FSH does not provide a big handicap at all except for the age group 43 or over.

             Emphasis on embryo freezing while increasing not only the chance of achieving a live pregnancy from one oocyte retrieval but for future babies from embryos derived from eggs obtained at a younger age (and thus better chance for successful pregnancy) can actually falsely lower our statistics when reporting pregnancy rates per fresh embryo transfer to SART.  Our own designed embryo freezing protocol provides better survival and pregnancy rates when the embryos are at the 2 pronuclear stage (Baker AF, Check JH, Hourani CL: Survival and pregnancy rates of pronuclear stage human embryos cryopreserved and thawed using a single step addition and removal of cryoprotectants. Hum Reprod Update May 1996;2:271 (CD-ROM), Item 1216).  The state of New Jersey with mandated insurance coverage for IVF allows insurance coverage for four oocyte retrievals and all of the frozen embryo transfers derived from those retrievals.  Thus our policy is to allow generally twice as many embryos to develop to day 3 as the couple intends to transfer and then pick the best ones for transfer and freeze the remaining decent day 3 embryos but the rest were frozen when they were one day old before dividing (the 2 pronuclear stage).

             You may ask how does this falsely lower the statistics on pregnancy rates per transfer?  The reason is that the ones we allowed to divide to day 3 may not have been the best ones.  The best ones can sometimes be detected by their morphology.  We published a study (Check JH, Summers-Chase D, Yuan W, Horwath D, Wilson C:  Effect of embryo quality on pregnancy outcome following single embryo transfer in women with a diminished egg reserve.  Fertil Steril 2007 Apr;87(4): 749-56) where we showed that with the transfer of a single embryo the pregnancy rate was only 3.8% when the embryo had only 4 cells (known as blastomeres) but was 9.5%, 38%, 40%, and 42.4% for 5, 6, 7, and 8 cells.  Thus sometimes by limiting the number of embryos to develop one may only transfer as an example a 5 cell and one 6 cell embryo whereas had all embryos been left to cleave there might have been two 8 cell embryos to transfer.  Nevertheless, the best embryos would be available for subsequent frozen embryo transfer.  So a strategy that a woman with NJ mandated insurance can use is do the egg retrieval using the method described and if no success do another egg retrieval saving many embryos for the future.  Thus if the couple loses their insurance and they no longer have IVF coverage even though they only used 2 of the 4 IVF cycles their remaining transfers with frozen-thawed embryos will still be covered by insurance.

             Nevertheless, for some couples they only want one pregnancy now.  For them we can change our policy and let all the embryos divide to day 3 and pick the best ones for fresh transfer giving them a higher pregnancy rate on that given retrieval.  This is especially important for people coming from long distances.  It should be noted that our freezing technique though best for 2 pronuclear embryos still works very well for day 3 embryos and blastocysts.

             Another way that statistics can be misleading is that some centers place some of the difficult cases that they see into an “experimental category” and these cases are not included in their statistics.  No one is excluded from our statistics.  Fortunately the bad cases do not bring down the statistics that much for Cooper.  For example, one of the IVF centers that reports one of the highest pregnancy rates per transfer in the world published a study showing that they achieved no live pregnancies in women whose FSH was >15 mIU/mL.  They only included in their study women who responded fairly well despite the high serum FSH and who had embryos worthy of transferring.  However despite a mean day 3 FSH of 22 mIU/mL and only a single embryo available for transfer we reported a live delivery rate of 31.0%, 75%, and 36.4% present for the group having a single embryo of 6, 7, or 8 blastomere transfers (Check JH, Summers-Chase D, Yuan W, Horwath D, Wilson C:  Effect of embryo quality on pregnancy outcome following single embryo transfer in women with a diminished egg reserve.  Fertil Steril 2007 Apr;87(4): 749-56).  Overall the live delivered pregnancy rate was 24% per transfer (which is good since some claim live pregnancies are not possible) which would lower our published live delivered pregnancy rate per transfer (we do not exclude these cases from SART data).

             Some of these cases used for the study on single embryo transfer were women who appeared to be in menopause and yet we reversed it (we will be discussing reversing menopause in a subsequent section)”.  But only half of these who have a retrieval go on to embryo transfer (either an egg was not there and possibly already released or they did not fertilize or the embryo arrested its growth before day 3).  Thus the addition of these cases to the category pregnancy rates per retrieval markedly reduces the pregnancy rate per retrieval statistics even more than the category pregnancy rate per transfer.

             Finally some centers will push couples to donor egg if they have failed 2-3 IVF cycles rather than lower their statistics.  Though sometimes we have been lucky with women with high FSH like the one who had three successes out of four IVF tries over eight years (Check JH, Katsoff B:  Three successful pregnancies with in vitro fertilization embryo transfer over an eight year time span despite elevated basal serum follicle stimulating hormone levels – Case report.  Clin Exp Obst Gyn 2005;32:217-221), another woman with diminished egg reserve did not conceive until her eighth try (and had identical twins) (Katsoff B, Check JH:  Monochorionic-diamniotic twins resulting from the transfer of a single embryo in a woman with decreased egg reserve:  A case report.  Clin Exp Obstet Gynecol 2005;32:141-142).

 Working with out-of-town patients

             We prefer to see you in person for the initial visit.  Subsequently you can get all or most testing in your local area including the blood work and ultrasounds needed for follicular maturation.  The information is faxed to us and we call you and tell you your next move.  Sometimes you come back for the procedures, e.g., IVF but we sometimes see patients work with them on the phone but never see them again because we can make all decisions by phone.  For these types of patients there is a $250.00 fee per month for our phone consultations.  Usually you can go to a regular blood lab, e.g., Quest or Lab Corp and an outside ultrasound facility and you do not need to go to another infertility center (though we do not oppose this).  Though not our preference in some cases we will do your initial interview by long distance telephone but only with our less senior associates.

 What clinical areas are we at Cooper Institute most noted for?

             As you will see when you look at the end of this message we provide references to the various publications concerning diagnosis and treatment of various disorders, with the majority of these articles concerning infertility.  We have divided these publications into categories and if you are interested in reading the entire article e-mail Laurie Long at Laurie@ccivf.com and she will e-mail you back that article.  Just indicate which number(s) you desire (see page __).

             The area of infertility that we are most noted for is reversing menopause and making women ovulate and working with women with diminished egg supply as evidenced by a high day 3 FSH level or history of poor response to FSH drugs, or low antral follicle count, or low inhibin B or anti-mullerian hormone levels.

             We established a technique to induce ovulation in women in apparent menopause over 25 years ago (Check JH, Chase J: Ovulation induction in hypergonadotropic amenorrhea with estrogen and human menopausal gonadotropin therapy. Fertil Steril 42: 919‑922, 1984).  By 1990 we published our experience with 100 cases of premature menopause and showed that we could make over 35% of these women ovulate (even though this was considered next to impossible at this time and showed that one could get about 20% of these women pregnant (Check JH, Nowroozi K, Chase JS, Nazari A, Shapse D, Vaze M: Ovulation induction and pregnancies in 100 consecutive women with hypergonadotropic amenorrhea. Fertil Steril 53(5):811‑816, 1990).  Over 20 years ago we showed live pregnancies were possible even in women in menopause whose FSH levels were over 100 and who were found on C-section to have almost no ovaries left (Check JH, Chase JS, Wu CH, Adelson HG: Case Report: Ovulation‑induction and pregnancy using an estrogen‑gonadotropin stimulation technique in a menopausal woman with marked hypoplastic ovaries. Am J Ob‑Gyn 160:405‑406, 1989).  Many subsequent successes were reported including women in apparent menopause needing IVF because of tubal problems (Check ML, Check JH, Choe JK, Berger GS: Successful pregnancy in a 42-year-old woman with imminent ovarian failure following ovulation induction with ethinyl estradiol without gonadotropins and in vitro fertilization.  Clin Exp Obst Gyn 2002;29:11-14).

             Related to our work with diminished egg reserve and ovarian failure (i.e., premature menopause) we have studied the effects of aging in both women and men.  For women we show that age rather than quantity of eggs is the best determinant for egg quality (Check JH, Peymer M, Lurie D: Effect of age on pregnancy outcome without assisted reproductive technology in women with elevated early follicular phase serum follicle-stimulating hormone levels.  Gynecol Obstet Invest 45:217-220, 1998).  However, are willing to try and have succeeded in achieving pregnancies in women 45 and above with their own eggs including one who was in menopause with a day 3 serum FSH of 63 mIU/mL and a husband with a very poor sperm count.  Interestingly they conceived with just an IUI not IVF after two cycles of restoring down-regulated luteal FSH receptors (Check JH, Check ML, Katsoff D: Three pregnancies despite elevated serum FSH and advanced age: Case report.  Hum Reprod 15(8):1709-1712, 2000).

             We were one of the first centers to show that pregnancies were possible after age 50 using donor eggs (Check JH, Nowroozi K, Barnea ER, Shaw KJ, Sauer MV: Successful delivery after age fifty: a report of two cases as a result of oocyte donation. Obstet Gynecol, 81:835‑836, 1993).  We are not reckless but we are open-minded to patients needs and requests.  Though we do nothing to try to entice women in their 50’s to try having children for fear that they may be at a greater physical risk we will sometimes even allow 59 year old women to have a baby (Check JH:  A 59-year-old woman gives birth to twins – when should a fertility specialist refuse treatment?  Clin Exp Obstet Gynecol 2008;35(2):93-97).

 Embryo hatching:

            Besides inventing a very successful slow cool technique for freezing as previously mentioned we published one of the first studies showing the importance of hatching frozen embryos (Check JH, Hoover L, Nazari A, O'Shaughnessy A, Summers D: The effect of assisted hatching on pregnancy rates after frozen embryo transfer. Fertil Steril 65:254‑257, 1996).  Embryo hatching is especially important for women of advanced reproductive age.

 MALE INFERTILITY

 Diagnosing the subferile male:

             Though all of our doctors are in the OB/GYN department we treat male infertility from the medical side.  We do have urologists, e.g., Dr. Joel Marmar or Dr. Mark Fallick available for testicular sperm aspiration or other surgical procedures.  Several studies focus on what is important on the semen analysis to diagnose the subfertile male, e.g., motile density levels (Check JH, Nowroozi K, Bollendorf A: Correlation of motile sperm density and subsequent pregnancy rates in infertile couples. Archives of Andrology. 27:113‑115, 1991) but we are especially known for showing that subnormal sperm morphology using strict criteria is not so accurate in diagnosing the subfertile male (Check JH, Adelson HG, Schubert B, Bollendorf A: The evaluation of sperm morphology using Kruger's strict criteria. Archives of Andrology. 28:15‑17, 1992; Check ML, Bollendorf A, Check JH, Katsoff D: Reevaluation of the clinical importance of evaluating sperm morphology using strict criteria.  Arch Androl 48:1-3, 2002;  Kiefer D, Check JH, Katsoff D: The value of motile density, strict morphology, and the hypoosmotic swelling test in in vitro fertilization‑embryo transfer. Arch Androl 37:57‑60, 1996.29-31).

 Antisperm antibodies:

             We have also conducted a lot of research studies with antisperm antibodies (Check JH, Adelson HG, Bollendorf A: Effect of antisperm antibodies on the computerized semen analysis. Archives of Andrology 27:61‑63, 1991).  We were one of the first IVF centers to show that IVF with ICSI was an effective therapy for sperm coated with antisperm antibodies (Check ML, Check JH, Katsoff D, Summers-Chase D: ICSI as an effective therapy for male factor with antisperm antibodies (ASA).  Arch Androl, 45:125-130, 2000).  However just as importantly we invented a technique to treat the sperm and neutralize the antibodies thus markedly improving the success and achieving pregnancies by IUI and saving the expense of IVF with ICSI (Bollendorf A, Check JH, Katsoff D, Fedele A: The use of chymotrypsin‑galactose to treat spermatozoa bound with antisperm antibodies prior to intrauterine insemination. Hum Reprod 9:484‑488, 1994).  Most other centers merely do IUI without first neutralizing the antibodies and thus rarely achieve a pregnancy with IUI when there is a significant antibody problem on the sperm.

 Medical treatment of sperm:

             We were pioneers in showing that clomiphene citrate could help improve semen quality in some males and also that it was helpful in males with varicoceles (varicose veins in their scrotum) thus saving men from surgery (which is frequently ineffective) (Check JH, Rakoff AE: Improved fertility in oligospermic males treated with clomiphene citrate. Fertil Steril 28:746‑748, 1977; Check JH: Improved semen quality in subfertile males with varicocele‑associated oligospermia following treatment with clomiphene citrate. Fertil Steril 33:423‑426, 1980).

 Discovering that sperm problems can lead to embryo implantation problems:

             One of our most important contributions to the knowledge of how the sperm may contribute to infertility was the discovery that sperm could fertilize an egg which may develop into a normal appearing embryo which does not implant (Check JH:  Sperm may be associated with subfertility independent of oocyte fertilization. Clin Exp Obstet Gynecol 2005;32:5-8).  One of the main tests to determine if the sperm may cause embryo implantation defects is to perform a single inexpensive test (known as the hypo-osmotic swelling (HOS) test (Check JH, Epstein R, Nowroozi K, Shanis BS, Wu CH, Bollendorf A: The hypo‑osmotic swelling test as a useful adjunct to the semen analysis to predict fertility potential. Fertil Steril 52(1):159‑161, 1989;  Check JH, Stumpo L, Lurie D, Benfer K, Callan C: A comparative prospective study using matched samples to determine the influence of subnormal hypo‑osmotic test scores of spermatozoa on subsequent fertilization and pregnancy rates following in vitro fertilization. Hum Reprod 10:1197‑1200, 1995).

             Thus conventional IVF-ET where 50,000 sperm are placed on top of each egg does not achieve pregnancies when the HOS test score is <50%.  But what is most frustrating is that it produces embryos that appear normal but these will not implant (Katsoff D, Check ML, Check JH: Evidence that sperm with low hypoosmotic swelling scores cause embryo implantation defects.  Arch Androl 44:227-230, 2000).  We have discovered that sperm may have attached to their membrane a toxic protein.  This protein impairs the function of the sperm membrane.  This impairment of the functional integrity of the sperm membrane is the basis for the HOS test.  When fertilization occurs one sperm gets into the egg but about 400 sperm attach to the zona pellucida.  Thus the sperm having this toxic protein attached to the sperm membrane is now attached to the egg membrane.  The egg membrane becomes incorporated into the embryo this membrane which transfers the toxic protein to the embryo membrane.  This toxic protein now impairs the function of the embryo membrane which prevents the embryo from attaching to the lining of the uterus known as the endometrium.  Thus these normal appearing embryos fail to result in a pregnancy because they will not stick to the uterine wall.  Nevertheless, the best way to achieve a pregnancy is by completely bypassing the attachment of the sperm with the toxic factor to the zona pellucida by simply performing ICSI (which is very effective) (Check JH, Katsoff D, Check ML, Choe JK, Swenson K: In vitro fertilization with intracytoplasmic sperm injection is an effective therapy for male factor related to subnormal hypo-osmotic swelling test scores.  J Androl 22:261-265, 2001).

             Of all the different semen parameters, the HOS test is the only one where even following IVF and the transfer of normal embryos following conventional oocyte insemination results in zero or close to zero pregnancies (Kiefer D, Check JH, Katsoff D: The value of motile density, strict morphology, and the hypoosmotic swelling test in in vitro fertilization‑embryo transfer. Arch Androl 37:57‑60, 1996).  Nevertheless despite this test being inexpensive and simple to perform, the large majority of IVF centers (even the most famous ones) do not perform this test despite the plethora of articles on this subject that we have published (probably because the test is not being pushed by a commercial company and some IVF centers are “so busy” that they are not keeping up on the literature).

             One of the best stories regarding this HOS test is the women who consulted Dr. Check because she had failed to become pregnant despite seven previous IVF-ET cycles and she was in the midst of her eighth.  But if she failed again she wanted to switch to Cooper if we could present a different approach.  Dr. Check found that her husband, who appeared to have superior sperm by standard semen parameters, had a low HOS test.  He advised the couple that they could continue with their present doctor but to advise them to do ICSI.  He even told them not to blame the center for not performing the test because many major IVF centers do not seem to be aware of the problem.  The patient called back and said that the other IVF center refuses to do ICSI because they do not believe in the test.  We advised her that we would be happy to take over the case but give that IVF center one more chance and tell them if they do not perform ICSI you will switch to Cooper.  They did and she became pregnant.  Nevertheless, it is now many years later and that center still does not perform the test.  A similar situation came up with multiple failures following IVF, again another husband had a low HOS test, this time this same center was willing to do ICSI if the couple signed a statement making them aware that their IVF center does not believe in this test (they have never published any negative studies) so she switched and came to us.  She conceived on her first attempt and delivered a baby and is now pregnant again with her first frozen embryo transfer.

 The aging male:

             As mentioned we have performed research as to how to best treat women and men of advancing reproductive age.  It is realized that males can achieve a successful pregnancy even when over 50 in contrast to women.  However, one very well known infertility center published data involving recipients using younger eggs and claimed they found a 25% reduction in pregnancy in males over 50.  Thus they concluded that it was related also to chromosome errors, i.e., meiosis errors.  However, we pointed out that they did not perform the HOS test.  We found that male aging considerably increases the frequency of HOS abnormality to 30% in men 50 and above.  Thus we showed that by measuring the HOS test and using ICSI when it is abnormal that we can completely overcome the effect of male aging and can obtain the same pregnancy rates using a donor egg model as younger males (Check JH:  Leveling the playing field for grandfather’s sperm.  Fertil Steril 2009;92:e29).

             Thus one of the major advantages at Cooper is that we treat both the male and female partner this allows us to know better when the male a contributing factor to the infertility and when is he not.

 The pros and cons of ICSI:

             There is no question that ICSI has been a tremendous additional tool to allow fertilization of eggs that could have never been achieved before.  For example it allows immature sperm from the testes, e.g., when a man has zero sperm in the ejaculate either due to obstruction or very poor sperm production, to now achieve pregnancy.  In fact we even achieved a pregnancy for a newlywed woman whose 38 year old husband of two weeks suddenly died of a heart attack using sperm that was extracted from the man’s testicles even though he was dead for 24 hours and was not on life support but in the refrigerator (Check ML, Check JH, Summers-Chase D, Choe JK Check DJ, Nazari A: Live birth after posthumous testicular sperm aspiration and intracytoplasmic sperm injection with cryopreserved sperm: Case report.  Clin Exp Obst Gyn 2002;29:95-96).  This case also shows to what extent we will go to fulfill a patient’s wishes.

             However, ICSI can be a double edged sword.  We have shown that embryos derived from ICSI have less chance of achieving a pregnancy than with conventional insemination (Check JH, Bollendorf A, Wilson C, Summers-Chase D, Horwath D, Yuan W:  A retrospective comparison of pregnancy outcome following conventional oocyte insemination vs. intracytoplasmic sperm injection for isolated abnormalities in sperm morphology using strict criteria.  J Androl 2007;28:607-612).  To add insult to injury ICSI adds an extra expense to an already expensive procedure (in some cases IVF centers charge over $2000.00 more to add ICSI!!).  Our knowledge from our own research has shown that sperm morphology using strict criteria does not cause infertility in general and thus where most IVF centers will do ICSI for normal morphology using strict criteria of 4% or less we showed that we can achieve a significant higher pregnancy rate at lower cost by just using conventional insemination.

             Even for unexplained infertility we presented data at the 2010 American Society of Andrology meeting that failed fertilization only occurs in 12.5% of cases.  Thus we suggested that the best strategy for unexplained infertility when doing IVF as a treatment is to do ICSI on half the eggs and conventional egg insemination on the other half, and if the embryo quality on the other half is equal, transfer the ones created by conventional insemination first because they have a better chance of implanting.

 Cervical mucus abnormalities:

             Some books on infertility state that the post-coital test is only of importance as a historical test.  We at Cooper disagree.  We believe that the demonstration of sperm properly moving in the cervical mucus at least 8 even 24 hours after intercourse when taken at the proper time is immensely important (Check JH: Letter to the editor. Re: The importance of the post‑coital test. Am J OB/GYN. 164:932‑933, 1991).

             The approach that most other infertility centers take is why bother checking this if one is going to do an IUI on every couple every cycle whether they need it or not.  What is wrong with the approach of IUI for everyone every cycle?  For one thing there is no evidence that performing IUI improves pregnancy outcome if there is nothing wrong with cervical mucus or with the sperm.  Of course many infertility specialists or gynecologists empirically put women on clomiphene citrate (even those with regular menses) and this drug frequently ruins the cervical mucus (Check JH, Adelson HG, Davies E: Effect of clomiphene citrate therapy on post‑coital tests in successive treatment cycles including response to supplemental estrogen therapy. Arch Androl, 32:69‑76, 1994).

             Unfortunately the infertility problems in the majority of women with regular menses are not helped by using clomiphene citrate empirically and chances of pregnancy may even be impaired by using them (Check JH, Nowroozi K, Wu CH, Adelson HG, Lauer C: Ovulation‑inducing drugs versus progesterone therapy for infertility in patients with luteal phase defects. Int J Fertil 33(4):252‑256, 1988; Check JH: Progesterone therapy versus follicle maturing drugs - possible opposite effects on embryo implantation.  Clin Exp Obst Gyn 2002;29:5-10).

             Thus not only to save money on IUI therapy and so save the inconvenience of time taking off from work, but some people for religious reasons, e.g., orthodox Jewish people or strict Catholics require normal intercourse rather than IUI.  Permission to perform IUI by their clergy may be given only under special circumstances.  And then there are some couples who just for personal reasons want to achieve a pregnancy the “old fashioned way”.  Thus we have created a lot of different ways to treat hostile cervical mucus without performing IUI (Check JH:  Diagnosis and treatment of cervical mucus abnormalities.  Clin Exp Obst Gyn 2006;33:140-142).  Probably our most famous study on treating mucus abnormalities involves the use of robitussin cough syrup or mucinex (Check JH, Adelson HG, Wu CH: Improvement of cervical factor with guaifenesin.  Fertil Steril 37:707‑708, 1982).

 Adverse effects of fertility drugs – mild ovarian stimulation:

             One of the reasons why 77% of women with at least one year of infertility who made mature follicles but have luteal phase defects became pregnant with just progesterone supplementation in the luteal phase with only a 4% miscarriage rate vs. only 11% with fertility drugs and a 67% miscarriage rate was certainly at least partially related to the fertility drug not correcting the problem but also to an adverse effect that this drug may have on the endometrium (Check JH, Nowroozi K, Wu CH, Adelson HG, Lauer C: Ovulation‑inducing drugs versus progesterone therapy for infertility in patients with luteal phase defects. Int J Fertil 33(4):252‑256, 1988; Check JH: Progesterone therapy versus follicle maturing drugs - possible opposite effects on embryo implantation.  Clin Exp Obst Gyn 2002;29:5-10).  In that same study 61% conceived with only a 6% miscarriage rate when the fertility drug failures were placed just on progesterone.  And we already mentioned the woman from Israel who failed to get pregnant after six years of fertility drugs and progesterone, 10 IVF cycles with 92 embryos transferred using fertility drugs and progesterone who conceived after one cycle of not taking fertility drugs and exclusively using progesterone in the luteal phase (Check JH, Check ML: A case report demonstrating that follicle maturing drugs may create an adverse uterine environment even when not used for controlled ovarian hyperstimulation.  Clin Exp Obst Gyn 28:217-218, 2001).

             We estimate that about 15% of women taking fertility drugs may create an adverse effect on the uterus.  But about 95% of women taking fertility drugs with elevated serum FSH levels have an adverse effect on the ability of the embryo to implant.  Some very well known IVF centers have found very poor pregnancy rates when performing IVF on these women with decreased egg reserve despite the transferring what appears to be good quality embryos (Scott RT, Toner JP, Muasher SJ, Oehninger S, Robinson S, Rosenwaks Z:  Follicle-stimulating hormone levels on cycle day 3 are predictive of in vitro fertilization outcome.  Fertil Steril 1989;51:651-654).

             One very well known and highly successful IVF center claimed no live deliveries in women of any age even with the transfer of an adequate number of embryos with normal morphology if the serum FSH was > 15 mIU/mL (Roberts JE, Spandorfer S, Fasouliotis SJ, Kashyap S, Rosenwaks Z:  Taking a basal follicle-stimulating hormone history is essential before initiating in vitro fertilization.  Fertil Steril 2005;83:37-41).

             Yet look at the next few tables which shows the Cooper pregnancy rate following IVF using mild ovarian stimulation in women with diminished egg reserve.  Notice no difference in pregnancy rates in those with mild decrease egg reserve (FSH 12-14), moderate decrease (FSH 15-17) and severe decrease (FSH >17).

 Pregnancy rates according to day 3 serum FSH following IVF-ET in women <35

 Pregnancy rates according to day 3 serum FSH following IVF-ET in women 36-39

Pregnancy rates according to day 3 serum FSH following IVF-ET in women 40-42

 Pregnancy rates according to day 3 serum FSH following IVF-ET in women 43-44

Interestingly the group of woman age 43-44 do relatively well when their day 3 FSH was normal.  Thus by using mild stimulation and thus not raising FSH any further and thus down-regulating or shutting down an FSH receptor to make a certain key implantation factor, a woman can achieve a perfectly normal pregnancy rate despite elevated day 3 serum FSH and diminished egg reserve.  The reason we know that this adverse effect of the fertility drug is directly on the embryo and not the endometrium is because frozen embryos from hyperstimulated women with decreased egg reserve do not successfully implant either.

             What is meant by minimal or mild ovarian stimulation?  We describe the technique in detail (Check JH, Summers-Chase D, Yuan W, Horwath D, Wilson C:  Effect of embryo quality on pregnancy outcome following single embryo transfer in women with a diminished egg reserve.  Fertil Steril 2007 Apr;87(4): 749-56; Check JH:  Mild ovarian stimulation.  J Assist Reprod Genet 2007;24:621-627) but it could vary from no fertility drugs at all, i.e., completely natural (55) to 150 IU FSH from day 5.

 Endometriosis:

             We were the first fertility center to show that mild endometriosis can cause infertility and that laparoscopic removal can improve pregnancy rates (Nowroozi K, Chase JS, Check JH, Wu CH: The importance of laparoscopic coagulation of mild endometriosis in infertile women. Int J Fertil 32:442‑444, 1987).  Though we still stand by these data we emphasize that the aforementioned study involved women who had failed to conceive after at least eight perfect treatment cycles.  Though we have many excellent Gyn surgeons in our group and one of them, Dr. Choe, has gained the reputation as one of the foremost reproductive surgeons in the country, we emphasize that the majority of infertile women with endometriosis can achieve successful pregnancies by treatment with progesterone supplementation after ovulation and paying attention to the luteinized unruptured follicle syndrome and treating it medically when necessary (Check JH: The association of minimal and mild endometriosis without adhesions and infertility with therapeutic strategies.  Clin Exp Obst Gyn 2003;30(1)13-8; Check JH, Adelson HG, Dietterich C, Stern J: Pelvic sonography can predict ovum release in gonadotropin‑treated patients as determined by pregnancy rate.  Hum Reprod 5(3):234‑236, 1990).  In fact one of our discoveries was that leuprolide acetate (lupron) or any gonadotropin releasing hormone (GnRH) agonist for that matter can frequently enable eggs to release from the follicles (failure to release is called the luteinized unruptured follicle syndrome or LUF) even when human chorionic gonadotropin (hCG) injections have failed (Check JH, Nazari A, Barnea ER, Weiss W, Vetter BH: The efficacy of short‑term gonadotrophin‑releasing hormone agonists versus human chorionic gonadotrophin to enable oocyte release in gonadotrophin stimulated cycles. Hum Reprod 8:568‑571, 1993).

 Besides infertility what else does the Cooper Institute treat?

 Miscarriage:

             Dr. Check’s Ph.D. thesis was that the role of progesterone in promoting fertility and preventing miscarriage is through the stimulation of immunomodulatory proteins.  Dr. Check was one of the pioneer’s in showing that supplementation of extra progesterone after ovulation can significantly reduce the risk of miscarriage (Check JH, Chase JS, Nowroozi K, Wu CH, Adelson HG: Progesterone therapy to decrease first‑trimester spontaneous abortions in previous aborters. Int J Fertil 32:192‑193, 197-199, 1987; Choe JK, Check JH, Nowroozi K, Benveniste R, Barnea ER: Serum progesterone and 17‑hydroxyprogesterone in the diagnosis of ectopic pregnancies and the value of progesterone replacement in intrauterine pregnancies when serum progesterone levels are low. Gynecologic and Obstetric Investigation. 34:133‑138, 1992).  We have also published one of the first studies showing that the use of progesterone during the first trimester did not lead to an increased risk of birth defects (Check JH, Rankin A, Teichman M: The risk of fetal anomalies as a result of progesterone therapy during pregnancy. Fertil Steril 45:575‑577, 1986).

             Although recently there has been data confirming that the use of progesterone beyond the first trimester could delay preterm labor, the first study on this subject was actually published in 1992 by our Cooper staff (Check JH, Lee G, Epstein R, Vetter B: Increased rate of pre‑term deliveries in untreated women with luteal phase deficiencies ‑ a preliminary report. Gynecol Obstet Invest 33:183‑184, 1992).  We have also found that in some instances low serum estradiol may be associated with miscarriage and we have set up standards for when to add estradiol at various weeks of pregnancies and according to whether fertility drugs were used or not (Check JH, Lurie D, Davies E, Vetter B: Comparison of first trimester serum estradiol levels in aborters versus nonaborters during maintenance of normal progesterone levels. Gynecol Obstet Invest, 34:206‑210, 1992).

             The staff at Cooper has also published data showing how to determine the right dosage of progesterone to use such as making sure that certain architectural changes of the endometrium (lining of the uterus) has been attained by one week after ovulation (Check JH, Dietterich C, Lurie D: Non-homogeneous hyperechogenic pattern 3 days after embryo transfer is associated with lower pregnancy rates.  Hum Reprod 15(5):1069-1074, 2000; Check JH, Gandica R, Dietterich C, Lurie D: Evaluation of a nonhomogeneous endometrial echo pattern in the midluteal phase as a potential factor associated with unexplained infertility.  Fertil Steril 2003 Mar;79(3):590-3).

             Our observation and therapeutic intervention of women during their first trimester does not only apply to those with a history of miscarriage but we, in contrast to many other infertility centers, carefully observe infertile patients conceiving in our practice and we treat when appropriate.  Besides treatment with progesterone and sometimes estradiol our studies on small for date gestational sac size associated with a poor prognosis (Nazari A, Check JH, Epstein R, Dietterich C, Farzanfar S: Relationship of small‑for‑dates sac size to crown‑rump length and spontaneous abortion in patients with a known date of ovulation. Obstet Gynecol 78(3) 369‑373, 19) led to our use of antibiotic therapy to prevent infection and leakage of amniotic fluid when appropriate.

             We have evaluated many proposed immune treatments for miscarriage including lymphocyte immunotherapy (Check JH, Tarquini P, Gandy P, Lauer C: A randomized study comparing the efficacy of reducing the spontaneous abortion rate following lymphocyte immunotherapy and progesterone treatment versus progesterone alone in primary habitual aborters. Gynecol Obstet Invest 39:257‑261, 1995; Check JH, Liss JR, Check ML, DiAntonio A, Duroseau M:  Lymphocyte immunotherapy can improve pregnancy outcome following embryo transfer (ET) in patients failing to conceive after two previous ET.  Clin Exp Obstet Gynecol 2005;32:21-22; Check JH, Liss J, Check ML, Diantonio A, Choe JK, Graziano:  Leukocyte immunotherapy improves live delivery rates following embryo transfer in women with at least two previous failures:  A retrospective review.  Clin Exp Obst Gyn 2005;32:85-88).  Our research has found that the immune system is very important in causing miscarriage but it is predominantly related to not making enough of a protein called the progesterone induced blocking factor (PIBF) which suppresses natural killer cells from attacking the foreign fetus.  But the reason for not making enough PIBF is usually not enough progesterone (Check JH, Ostrzenski A, Klimek R: Expression of an immunomodulatory protein known as progesterone induced blocking factor (PIBF) does not correlate with first trimester spontaneous abortions in progesterone supplemented women.  Am J Reprod Immunol 37:330-334, 1997).  However, in a minority of cases the fetus does not induce enough of the progesterone receptors in the white blood cells that interact with progesterone to make PIBF (they are called gamma/delta T cells).  However, white blood cells injections which are 100-1000 times more powerful to stimulate progesterone receptors and we have found that lymphocyte immunotherapy increases PIBF levels (Check JH, Arwitz M, Gross J, Peymer M, Szekeres-Bartho J:  Lymphocyte immunotherapy (LI) increases serum levels of progesterone induced blocking factor (PIBF).  Am J Reprod Immunol 37:17-20, 1997).  We have also found lymphocyte immunotherapy to be effective for women failing to have a successful IVF cycle mostly by reducing miscarriage (Check JH, Liss JR, Check ML, DiAntonio A, Duroseau M:  Lymphocyte immunotherapy can improve pregnancy outcome following embryo transfer (ET) in patients failing to conceive after two previous ET.  Clin Exp Obstet Gynecol 2005;32:21-22; Check JH, Liss J, Check ML, Diantonio A, Choe JK, Graziano:  Leukocyte immunotherapy improves live delivery rates following embryo transfer in women with at least two previous failures:  A retrospective review.  Clin Exp Obst Gyn 2005;32:85-88).  We have also shown that small uterine fibroid tumors do not negatively impact IVF implantation or miscarriage rates, thus saving women from major surgery that is not needed.

             Nevertheless we are very good at removing submucosal fibroids (especially Dr. Choe) who also excels at correcting uterine abnormalities.  We have also shown that small uterine fibroids do not impact IVF implantation or miscarriage rates thus saving women from having major surgeries (Check JH, Choe JK, Lee G, Dietterich C: The effect on IVF outcome of small intramural fibroids not compressing the uterine cavity as determined by a prospective matched control study.  Hum Reprod 2002;17:1244-1248; Check JH, Krotec JW:  The patient with fibroids.  In IVF in the medically complicated patient:  a guide to management, NS Macklon (ed), United Kingdom, Taylor & Francis, 2005, pp 139-157).

             Dr. Check has written five editorials on the practical treatment of miscarriage:

 1.         A practical approach to the prevention of miscarriage:  part 1 – progesterone therapy (request #______).

2.         A practical approach to the prevention of miscarriage Part 2 – active immunotherapy (request #______).

3.         A practical approach to the prevention of miscarriage Part 3 – passive immunotherapy (request #______).

4.         A practical approach to the prevention of miscarriage Part 4 – role of infection (request #______).

5.         A practical approach to the prevention of miscarriage Part 5 – the antiphospholipid            syndrome as a cause of spontaneous abortion (request #______).

 You are welcome to request these editorials by e-mail from Laurie Long at Laurie@ccivf.com

 Sex selection and family balancing:

             We have published several papers trying to improve the odds of increasing the chance of either a male or female child without spending a lot of money (we do not charge any extra).  We seem to achieve a 75% chance of a male offspring with our male selection technique (Check JH, Katsoff D: A prospective study to evaluate the efficacy of modified swim‑up preparation for male sex selection. Hum Reprod, 8(2):211‑214, 1993).  Though we found a method to increase the percentage of female sperm significantly (Check ML, Bollendorf A, Check JH, Hourani W, Long R, McMonagle K: Separation of sperm through a 12-layer Percoll column decreases the percentage of sperm staining with quinacrine.  Arch Androl 44:47-50, 2000) but for some reason failed to increase the percentage of female babies (Bollendorf A, Duroseau M, Hourani W, Mcmonagle K, Check JH:  The efficacy of sperm separation by a 12 layer Isoprep column on X bearing sperm enrichment and subsequent percentage of female births.  In:  International Proceedings of the 8^th International Congress of Andrology, Medimond Editore, Pgs. 71-73, 2005).

             Though our male sex selection technique is very inexpensive it is far from perfect.  The most accurate method is to do IVF with PGD and only replace the male or the female embryos.  Unfortunately this is the most expensive since PGD adds an extra 3-4 thousand dollar charge.  Though we send out to a laboratory the cell of the embryo that we biopsied and thus the genetic center not Cooper receives the PGD fee, to help couples we cut our IVF price in half for those having PGD for sex selection.

             We also work with Microsort® which provides a high percentage of female sperm but unfortunately is not only expensive (about $4000.00) but the yield of sperm is low thus IVF provides a much better pregnancy rate than IUI.  We also drop our price in half for those having sperm processed by Microsort® for sex selection if they are having IVF with us.

 Cooper Institute is just the perfect size

             Too little sun exposure and you get vitamin D deficient and too much sun you get sunburn and skin cancer.  A single doctor infertility center has the theoretical advantage of getting to know your doctor better and the doctor knowing you better but it has the distinct disadvantage in that the doctor can not be in 2 or 3 places at one time and can not work every day so compromises in patient care have to be made.  An extremely large practice has the benefit of increased experience and usually convenience of appointments but loses the personal touch.  You feel like you are part of an assembly line.

             There are some IVF centers that do 2000-3000 IVF cycles a year and yet only have about 50 employees.  At Cooper we have 105 employees and average about 700 retrievals a year.  We have 7 full-time and one part-time embryologist to take care of an average of 2 IVF-ET cycles per day.  Compare the number of embryolgists in other IVF centers doing a lot more cycles and we do not just have embryologists taking care of the process – we have 4 additional andrologists taking care of the sperm part.

 How do we provide experience and yet personal care?

             First though we are a team of doctors not just a group of individual doctors using one IVF center, we want you to have your own personal physician in our group.  All the doctors are available to do your initial consultation and that doctor remains your personal physician thereafter unless you decide to change to another doctor in the group.  New patient appointments are made according to which doctor you want to see rather than on a rotating basis.  That doctor however has the back-up of the other physicians in case one cannot be at two places at once.

             The exception is when we are doing IVF.  There are just three doctors doing the retrieval – Jung Choe, Deanna Brasile and Rachael Cohen.  They do it on a weekly rotational basis.  All have similar pregnancy rates.  This allows us to provide you with our best skilled physicians doing the mechanical procedures and frees up our head physician who has the most knowledge of reproductive and medical endocrinology and experience and has the most innovative and creative ideas for more consultations.  Dr. Check is thus always available to do more consults and to be available to help nurses with their phone calls, etc.

             During the IVF week we generally have the doctor doing IVF to make the decisions on day to day management but the protocol would have been established by your primary doctor.  If the nurses question a decision or for that matter if you have concerns your primary doctor can be consulted on that decision or all your daily decisions during an IVF cycle.

             The nurses doing call backs for non-IVF patients will generally consult your primary doctor for the decision or another physician if your primary doctor was not available.

             Highly trained ultrasonographers do the ultrasounds.  Many office procedures, e.g., post-coital tests are performed by nurses allowing the doctors more time to spend with patients in consultation.  It should be noted that there is very little turnover at Cooper and many of our staff, e.g., andrologists, nurses, embryologists, ultrasonographers have been here for over 20 years.  Thus you will find our nurses extremely knowledgeable and frequently know as much as the physicians so do not be afraid to ask them questions or get their opinions.

             Our large staff allows us to work all seven days (only IVF and IUI on Sunday’s).  IVF is open all year except for one week closure during Christmas.  You would think that such services would have to be very expensive.  However, we have a heart and we ask you to compare prices – we are one of the least expensive infertility centers in the country despite our extensive experience.

 Peer recognition:

             Dr. Check has been on most TOP DOC lists since the beginning of TOP DOCs both in Pennsylvania and New Jersey.  This website was updated in June 2010 and he was voted as TOP DOC for reproductive endocrinology and infertility in Philadelphia Magazine, the May 2010 issue.  He just received notice that he will be a TOP DOC in New Jersey Monthly in the  October 2010 issue.

            Dr. Samuel Jacobs was listed in TOP DOC South Jersey Magazine, 2008.

            Dr. Jung Choe is known especially locally but also nationally as one of the top reproductive surgeons.

What other types of cases are seen at Cooper:

             We see all types of reproductive endocrine disorders, e.g., amenorrhea (no period) dysmenorrhea (bad cramps), pelvic pain, excess hair, frequent or heavy menstrual periods.  Dr. Check especially has figured out difficult diagnoses and rendered satisfactory treatment for conditions that had stymied may previous physicians.  Dr. Check will also see patients with endocrine disorders other than diabetes.

Donor Egg Program:

             Probably the most expensive area of IVF is the donor egg program.  We believe we are the most cost effective IVF center in the country with donor eggs.

             Let us give you an example there is one IVF center claiming to have the highest live delivered success rate at 80%.  On their website they compare their statistics to other centers by name (including ours).

             Because of concept of pregnancy rates per oocyte harvest (i.e., the chance of a live delivery from one set of fertilized eggs before needing to fertilize a new set of eggs and thus counting the frozen embryos made) we only allow twice as many embryos to divide to day 3 as intended to transfer and choose the best 1 or 2 embryos to transfer.  This is important to understand when we compare cost effectiveness to the IVF center that “stands above the rest” (most IVF centers including ours) have a live delivered pregnancy rate of 50%.

             One of the ways that this IVF center can obtain these rates is to be a very good technical IVF center with good physicians and embryo staff.  The next thing is to select the right donors and select the right patients (i.e., do not take women failing with donor oocytes in other places or women turned down by other IVF centers for problems, e.g., too thin of an endometrium, etc.).  We being known as problem solvers and because of our low price see a higher percentage of a difficult recipient than others.  Also because of our low price someone who just has problems where she will not conceive can try many more cycles with us before her money runs out so this would lower our pregnancy rates.

             However, probably the biggest difference is success is probably related to the fact that part of the reason why our price is only 1/3 of this other center is that most of our patients hare the eggs with either an infertile woman providing the eggs or another recipient.  If a woman elects to keep all the eggs our price instead of being 1/3 of this TOP center is 50% as high.  Thus the center in question is very good at finding the best embryo but tends to waste the rest.  They allow all the embryos to cleave to blastocyst stage even through some potential future pregnancies will be lost.  Remember even though we start with only half the number of eggs we still only allow to cleave to day 3 double the amount to transfer and freeze the rest when they are only 1 day old.

             We could improve our rates by either not sharing the eggs or at least allowing all the embryos to cleave to day 3 and pick the best.  The reason we do not do this is that most of the donors will not be available in the future so the couple if they want another child with identical genes in the future they would want to have a supply of frozen embryos.

             Let us show you the difference in cost effectiveness with us and the TOP center

 Price for us approximately $10,000 vs. $30,000 for TOP center

50% pregnancy rate vs. 80%

First 50 pay

Cooper - $10,000                                TOP - $30,000

We get a 40% pregnancy rate following frozen embryo transfer.  Thus we would expect the next 20 patients to have a success for a cost of ~$3,000.00

Next 20 patients – their cost:

Cooper - $13,000                                TOP - $30,000

Thus Cooper has 30 patients left not pregnant vs. TOP center 20 at this time.

Suppose no frozen embryos are left in either center.  Cooper needs another retrieval for 30 and TOP center only 20.

At 50% rate 15 of the Cooper patients concur

So for patients 71-80 costs are:

Cooper - $10,000 plus $3,000 for frozen plus $10,000 for another retrieval

Total Cooper cost - $23,000               TOP center - $30,000

For patients 81-85:

Cooper cost - $23,000                         TOP center cost - $60,000

The 15 patients left at Cooper now have frozen embryo transfers and we expect 6 to conceive for patients 86-90:

Cooper cost - $26,000                         TOP center cost - $60,000

            The list of publications will show you the diversity of conditions we treat (check category Reproductive endocrine disorders and medical endocrine disorders).

 Research publications:

            As you will see at the end is a list of publications separated by category.  If any article interests you we can e-mail it to you free of charge, contact Laurie Long at Laurie@ccivf.com.

Summary of the benefits of Cooper Institute for Reproductive Hormonal Disorders:

1.      We provide personalized service.

2.      We are very experienced.

3.      We have a lot of unique programs designed to save you money     (e.g., free IVF using the shared oocyte system).

4.      We have a heart and try to charge the least amount of money       consistent with the survival of the institution.

5.      We succeed when others fail because of our research          experience.

6.      We are dictated by your needs and not the needs of the        institution, e.g., pushing you into donor eggs when you clearly     want to keep trying with your own even if your prognosis is     not    great.

7.      We are not just an IVF center.  We are able to help a lot of    couples achieve pregnancies without having to go to IVF.

8.      Our highly successful frozen embryo program enables you to        really get your best “bang for your buck” when you need IVF       since future babies can also be inexpensively achieved.

We all care about you and your needs and your concerns and consider all of this when doing our consults.  Thank you for visiting our website.

ALL MATERIAL CONTAINED WITHIN THIS SITE © 2003 BY COOPER INSTITUTE FOR REPRODUCTIVE HORMONAL DISORDERS, P.C.
ALL RIGHTS RESERVED.

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