David R. Meldrum, MD

Publications
I have published over 100 papers and 65 other contributions, mostly chapters, and 3 books. Below are some highlights starting with the most recent:

1) Meldrum DR, Burnett AL, Dorey G, Esposito K, Ignarro LJ. Erectile hydraulics: maximizing inflow while minimizing outflow. J Sex Med 2014;11:1208-20.

This was my 4th major review on erectile function, written with a top urologist at Johns Hopkins, a researcher in Bristol, Great britain, a MD/PhD in Italy, and Lou Ignarro, PhD, our UCLA Nobel Laureate.

2) Meldrum DR, de Ziegler D. Introduction: Risk and safety management in infertility and assisted reproductive technology. Fertil Steril 2013;100:1497-8.

I wrote this with several other pilots who practice IVF or are involved in safety of aviation. If we could apply all of the safety measures that are routine in aviation, most medical errors would not occur.

3) Meldrum DR. Pregnancies and deliveries per fresh cycle are no longer adequate indicators of invitro fertilization program quality: how should registries adapt? Fertil Steril 2013;100:620-1.

This was an editorial I wrote trying to encourage registries world-wide to report fresh and frozen cycles together. With the newer cryopreservation using vitrification and the findings that embryos implant better and the resulting pregnancies are less complicated by avoiding embryo transfer into a stimulated uterus, it no longer makes sense to report them separately.

4) Meldrum DR, Fisher AR, Butts SF, Su HI, Sammel MD. Acupuncture - help, harm, or placebo? Fertil Steril 2013;99:1821-4.

Studies examining the potential benefits of acupuncture for IVF success have largely been of poor quality. Together with four researchers with training in statistics I collected studies we felt were of reasonable quality and showed that there appears to be a placebo effect of acupuncture but no evidence thus far of a specific treatment effect.

5) Meldrum, DR. Aging gonads, glands and gametes: immutable or partially reversible changes? Fertil Steril 2013;99:1-4.

I organized this "views and reviews" section of our journal on aging gonads, glands and gametes as a treatise on reduced fertility due to aging. As part of the series I co-authored a review on androgens and aging. Testosterone levels decline, and evidence points to beneficial effects of boosting testostrone levels around the aging egg.
6) Rosen M, Meldrum, DR. Can FSH co-trigger prevent OHSS? Fertil Steril 2012 97:534-5.
This short piece was an editorial comment on an intriguing new way of preventing ovarian hyperstimulation, which is an uncommon but potentially serious complication related to ovarian stimulation.
7) Meldrum DR. Preventing severe OHSS has many different facets. Fertil Steril 2012 97:536-8.
            I organized the March 2012 “Views and Reviews” section of Fertility and Sterility and this is my summary of the reviews written by my invited authors and also some points not covered in their reviews.
8) David R. Meldrum, M.D., Joseph C. Gambone, D.O., M.P.H., Marge A. Morris, M. Ed., R.D., C.D.E., Katherine Esposito, M.D., Ph.D., Dario Giugliano, M.D., Ph.D., Louis J. Ignarro, Ph.D. Lifestyle and metabolic approaches to maximizing erectile and vascular health. Int J Impot Res 2012;24:61-8.
            This was the third major review article I have written on erectile and vascular health. This piece concentrated more on the role of oxidative stress and antioxidants but it also was a good general review of the role of nitric oxide in erectile and vascular function.
9) de Ziegler D, Streuli I, Meldrum DR, Chapron C. The value of growth hormone supplements in ART for poor ovarian responders. Fertil Steril 2011;96:1069-1076.
I co-authored this review on the value of growth hormone for ART poor responders. The collective information shows at least a 3-fold increase in the delivery rate. Poor responders have lower levels of IGF-1, the body chemical through which growth hormone acts, and higher growth hormone levels in the fluid around the egg correlate with a higher pregnancy rate.
10) Meldrum, DR, DeCherney. The Who, Why, What, When, Where and How of Clinical Trial Registries. Fertil Steril 2011;96:2-5.
            I co-authored this with our previous editor. Randomized clinical trials must be registered online before the first patient is entered into the study to assure the study has been conducted appropriately. Together with our new editors, we decided to draw a line in the sand and not accept any further manuscripts not appropriately registered.
11) Meldrum, DR, Sammel MD, Barnhart K. The Null Hypothesis- closing the gap between good intentions and good studies. Fertil Steril 2011;96:6-10.
            In this review, written with two biostatisticians, I emphasized that if an investigation is not properly planned, executed and analyzed appropriately, it is very difficult for the journal’s reviewers to assure themselves that the authors’ conclusions are correct and can be relied upon.
12) Meldrum, DR, Gambone JC, Morris M, Meldrum DAN, Esposito K, Ignarro LJ: The Link Between Erectile and Cardiovascular Health: The Canary in the Coal Mine. Amer J Cardiol, 2011;108:599-606.
            This was my second major review of erectile and vascular function, emphasizing the link between erectile problems and heart disease. Poor lifestyle choices are major contributors to both problems and poor erectile function can sometimes be a critical warning sign of actual or impending serious cardiovascular events, even including sudden death.
13) Meldrum DR, Gambone JC, Morris MA, Ignarro LJ. A multifaceted approach to maximize erectile function and vascular health. Fertil Steril 2010;94:2514-20.
            This was our first review of the effects of lifestyle on erectile and vascular health. Being in a fertility journal, this review emphasized positive effects of good lifestyle choices and supplements on sperm, testosterone production, and erectile function.
14) Meldrum DR, Chang RJ, de Ziegler D, Schoolcraft WB, Scott RT, Pellicer A: Adjuncts for ovarian stimulation- when do we adopt “orphan indications” for approved drugs? Fertil Steril, 2009,92:13-18.
            Unfortunately, most treatments are based on expensive new drugs. Obtaining FDA acceptance of a new drug treatment is an expensive process, so drug companies won’t invest the resources without being assured of patent protection and major profits. However, in our specialty there are many examples of where existing medications that are on the market have been found to be helpful for fertility and the only way we can use them is “off label”. Often the drug in question is no longer patent-protected and once the research is done, multiple companies could profit from their investment. In this editorial we reviewed several such drugs and proposed a decision-making process that can be used by clinicians in deciding when there is enough information to use it for a new “unapproved” indication. The most prominent example is growth hormone. In spite of compelling evidence of major benefit for certain low prognosis IVF patients, most practitioners hesitate to use it. Hopefully this editorial and #4 above will help to turn the tide of opinion.
15) Meldrum DR, Cassidenti DL, Rosen GF, Yee B, Wisot AL: Oral contraceptive pretreatment and half dose ganirelix does not excessively suppress LH and may be an excellent choice for scheduling IUI cycles. J Assist Reprod Genet, 2008;25:417-20.
It has been found to be helpful for FSH/IUI cycles to use a GnRH antagonist like ganirelix to prevent ovulation and allow smaller follicles to mature. In this trial we showed good results with using half the usual dose of ganirelix when preceding the cycle with an oral contraceptive to synchronize the follicles. We proposed that this approach could be used for IVF cycles and with less suppression of LH, a simpler regimen of only FSH could be used.
16) Levin ER, Rosen GF, Cassidenti, DL, Yee, B, Meldrum, D, Wisot, A, Pedrum, A: Role of vascular endothelial cell growth factor in Ovarian Hyperstimulation Syndrome.  J Clin Invest 1998;102:1978-85
            In this study, RPMG physicians worked with basic scientists at UC Irvine to help to further define the role of vascular endothelial growth factor in the ovarian hyperstimulation syndrome. By using an antibody to block the action of VEGF we showed that 98% of the effect of follicular fluid in high responders on vascular permeability was due to VEGF.
17) Meldrum DR, Silverberg KM, Bustillo M, Stokes L:  Success rate with repeated cycles of in vitro fertilization-embryo transfer.  Fertil Steril 1998;69:1005-9          
            Using national data we showed that success rates with IVF were similar for the first three cycles, then dropped by about 40%, presumably because the most fertile patients had already been successful.
18) Thompson KA, La Polt PS, Rivier J, Henderson G, Dahl K, Meldrum DR:  Gonadotropin requirements of the developing follicle.  Fertil Steril 1995;63:273-6
            In this study we showed that a dose of 50 IU of hCG restored bioactive LH/hCG levels to normal in women suppressed with a GnRH antagonist. This led others to use this dose together with pure FSH for women with low gonadotropin levels. That approach allows use of an FSH pen and small adjustments of dosage to limit the risk of multiple pregnancy in these women.
19) Meldrum, DR, Rivier J, Garzo G, Wisot, A, Stubbs C, Hamilton, F.  Successful pregnancies with unstimulated cycle oocyte donation using an antagonist of gonadotropin-releasing hormone.  Fertil Steril 1994:61:556-7
            In this study we were first to report success with a modified natural cycle IVF for transfer of a single embryo. Use of a GnRH agonist allows the follicle to fully mature without the timing and success of the egg retrieval being disturbed by premature release of the egg. Other groups have gone on to do larger series of patients, but its lower success rate has limited its use.
20) Schoolcraft W, Sinton E, Schlenker T, Huynh D, Hamilton F, Meldrum DR: Lower pregnancy rate with premature luteinization during pituitary suppression with leuprolide acetate. Fertil Steril 1991;55:563
            We were the first to report a reduced success rate in IVF when the progesterone level was increased on the day of hCG administration. This was recently confirmed in a large number of patients in France. That group and ours had initially shown that it was mainly women on a high dose of FSH and with a low ovarian response that showed this effect, but their most recent study showed that it occurs in normal responders as well. Unfortunately its use is limited by the lower accuracy of current methods for progesterone measurements and difficulty in predicting when the level would be too high. With improved embryo cryopreservation with vitrification, it could be a way of predicting which patients would benefit from delayed transfer in a controlled hormone replacement cycle.
21) Cedars MI, Surey E, Hamilton F, Lapolt P, Meldrum DR: Leuprolide acetate lowers circulating bioactive luteinizing hormone and testosterone concentrations during ovarian stimulation for oocyte retrieval. Fertil Steril 1990;53:627
            In this study we showed that bioactive LH levels were very low with a full dose of Lupron. Based on this paper and on papers showing improved success with using both FSH and LH for ovarian stimulation in GnRH agonist cycles, we believe that a mixture of hMG (contains LH and FSH) and pure FSH is best for full dose lupron cycles and where lupron is combined with oral contraceptive pretreatment.
22) Meldrum DR, Wisot A, Hamilton F, Gutlay‑Yeo, AL, Marr B, Huynh D: Artificial agonadism and hormone replacement for oocyte donation. Fertil Steril 1989;52:509
            Prior to this report, for egg donation cycles it had been difficult to synchronize the donor and recipient, which did not allow embryo transfer on the ideal day of progesterone administration. We demonstrated by using Lupron to suppress the recipient’s ovarian function, the progesterone could be started for ideal synchronization, which is generally the day of or the day after the donor’s egg retrieval.
23) Meldrum DR, Wisot A, Hamilton F, Gutlay AL, Kempton W, Huynh D: Routine pituitary suppression with leuprolide before ovarian stimulation for oocyte retrieval. Fertil Steril 1989;51:455
            We were the first to suggest, based on our excellent results and the major advantages of synchronization of the follicles and prevention of premature ovulation, that a GnRH agonist should be used routinely for IVF. Still, it took a few years before virtually all IVF programs world-wide were using this adjunct in most or all initial IVF cycles.
24) de Ziegler D, Cedars MI, Randle D, Lu JKH, Judd HL, Meldrum DR: Suppression of the ovary using a GnRH agonist prior to stimulation for oocyte retrieval. Fertil Steril 1987;48:86
            In this study, we were one of the first to use a GnRH agonist before IVF cycles. One of the major benefits was an improved response in poor responders by synchronizing the follicles.
25) Boyer P, Territo MC, de Ziegler D, Meldrum DR: Ethiodol inhibits phagocytosis by pelvic peritoneal macrophages.  Fertil Steril 1986;46:715
            Studies have observed improved fertility for 4-6 months after HSG using an oily dye, ethiodol. Together with a UCLA basic scientist we demonstrated that one mechanism of this effect is that the oily dye prevents cells called macrophages from being able to engulf and remove sperm from around the egg.
26) Meldrum DR, Chetkowski RJ, Steingold KA, Randle D: Transvaginal ultrasound scanning of ovarian follicles. Fertil Steril 1984;42:803
            In this study we demonstrated that we could obtain clearer scans of the ovary by trans vaginal scanning. Up until that time, monitoring of ovarian response was done abdominally, with a full bladder to act as an acoustic window. I reached this conclusion after attending an ultrasound course. Of course this led eventually to trans vaginal egg retrieval, now the routine method for egg collection.
27) Chetkowski RJ, Nass T, Matt D, Meldrum DR: Optimization of hydrogen‑ion concentration during aspiration of oocytes and culture and transfer of embryos. J in Vitro Fert Embryo Transfer 1985;2:207
            In this study we demonstrated how use of a pediatric isolette maintained osmolarity and pH of media for eggs and embryos, and how susceptible media in a small volume in culture dishes was to changes in these parameters. One academic program that I was asked to help early in the development of IVF techniques was actually failing to achieve fertilization because they were using a small volume of fluid in a dish. By simply increasing the volume of media in the dish, they immediately corrected the problem.
28) Meldrum DR, Chang RJ, Lu J, Vale W, Rivier J, Judd HL: "Medical oophorectomy" using a long‑acting GNRH agonist‑a possible new approach to the treatment of endometriosis. J Clin Endocrinol Metab 1982;54:1081
            In this rapid communication we were first to describe the use of a GnRH agonist in women with endometriosis. Of course this led to the use of Lupron, which is now widely used to give symptomatic relief in women with this disease.
29)  Tataryn IV, Meldrum DR, Frumar AM, Lu KH, Judd HL: LH, FSH and skin temperature during the menopausal hot flash. J Clin Endocrinol Metab 1979;49:152   
            Working under Howard Judd, a UCLA faculty member with a lifelong interest in the menopause, we demonstrated that release of pituitary gonadotropins occurred with each hot flash. I remember as a junior faculty person finding a method described whereby the hot flash could be objectively demonstrated by recording skin temperature. We then rigged up a recording device that allowed us to make this landmark observation. Subsequently we and others used it to objectively monitor treatment modalities. Ivanna was our research fellow and a fellow Canadian who now practices in Alberta.
30) Meldrum DR, Abraham GE: Peripheral and ovarian venous concentrations of various steroid hormones in virilizing ovarian tumors. Obstet Gynecol 1979;53:36
            This was one of my earliest papers where we demonstrated that most ovarian testosterone producing tumors were associated with circulating levels over 200 ng/dl. Guy was a brilliant physician who was first to define a practical method for blood estrogen measurements.
            Well, I’ve enjoyed going back over my best contributions to my chosen field of study. As you can see my present activity is focused more on review articles, which are much more powerful in improving patient care. I’m grateful to UCLA for the training I received and the further development as full-time faculty of my ability to see potential new modalities for refining care of our patients. I continue to enjoy passing on what I’ve learned to our current fellows at UCSD.

Appointments:

I am no longer seeing patients, but I continue to be the scientific director of Reproductive Partners Medical Group in La Jolla, where we have made it a prority to transfer a single high quality embryo in as many of our patients as possible, to avoid the very significant complications of multiple pregnancy for both mother and her newborn. We currently have one of the highest implantation rates in the nation. To learn more or to see one of our physicians, go to our website.