Candid Patient Reviews of
Dr. Eric Daiter

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Dr Eric Daiter has served Monmouth and Middlesex Counties of New Jersey as an infertility expert for the past 20 years. Dr. Daiter is happy to offer second opinions (at the office or over the telephone) or new patient appointments. It is easy, just call us at 908 226 0250 to set up an appointment (leave a message with your name and number if we are unable to get to the phone and someone will call you back).


"I always try to be available for my patients since I do understand the pain and frustration associated with fertility problems or endometriosis."


"I understand that the economy is very tough and insurance companies do not cover a lot of the services that might help you. I always try to minimize your out of pocket cost while encouraging the most successful and effective treatments available."

NJ Center for Fertility and Reproductive Medicine - Infertility Tutorials

Complications of Menotropins (detailed)
Complications of these medications (menotropins) might include multiple pregnancies, ovarian hyperstimulation syndrome, premature LH surge, irregular follicular development, and ovarian torsion. Theoretically, there is a potential association with ovarian cancer.

(1) multiple pregnancy

* Multiple pregnancies associated with menotropins are more common and of higher order than those associated with clomiphene citrate. In natural cycles, the twinning rate (in the USA) is about 1 in 90 and the triplet rate about 1 in 8000. In clomiphene cycles, the twinning rate is about 1 in 12 and the triplet rate is about 1 in 150. In menotropin cycles, the twinning rate is about 1 in 4, the triplet rate about 1 in 20 and quadruplets or quintuplets are uncommon.

* At the point of triplets or more, the combined risks of morbidity or mortality to the pregnant woman and fetuses are greater than that of the selective reduction procedure (at a center with significant experience in performing this procedure). Selective reduction is a procedure that is done to reduce the number of pregnancies, typically down to two. It does involve terminating one or more growing pregnancies and therefore should be discussed carefully by the couple. A decision on selective reduction may involve moral, ethical, religious, medical, personal and emotional factors. The decision ideally should be made prior to the initiation of a cycle, while the couple is able to consider the variables without time limitations or the stress of knowing that there is a triplet or greater order multiple pregnancy growing.

(2) ovarian hyperstimulation syndrome (OHSS)

* OHSS is a potentially serious and often uncomfortable complication of menotropin therapy. The syndrome may occur days to a few weeks following ovulation (the Profasi shot) when more than one follicle has developed. OHSS is caused by an unknown process that occurs within the ovaries, producing a substance (not yet identified) that allows the water from within the body's blood to leak out of the blood vessels into the pelvis and abdomen (resulting in abdominal distention, bloating and dehydration). The ovaries become very fragile (easily traumatized) so that any sudden motion or even relatively mild flexion (bending) at the hip (such as typing at a desk) can cause pelvic pain. The patient must drink large amounts (1-2 liters) of a balanced electrolyte solution (Gatorade or Pedialyte are good) to replace the water that is collected in the pelvis (rehydration). She also must try to limit her activities to avoid ovarian trauma and pain.

* In severe cases of OHSS, hospitalization with an intravenous catheter (for fluid replacement) may be required. Rarely, fluid can also collect around the lungs to limit breathing (resulting in shortness of breath), or the dehydration can be so severe that the patient is at risk for renal (kidney) failure (shutdown), abnormal blood clotting and/or pulmonary emboli. The treatment of OHSS is fluid replacement, limited activity (possibly bedrest) and supportive care. Medications to assist in kidney function (such as IV dopamine) and/or mechanical removal of some of the abdominal fluid that has collected (with a needle ideally under ultrasound guidance) can be quite helpful.

* As a rule, OHSS will not occur if the hCG (Profasi) injection is withheld. This results in the slow removal of the follicles that have developed and also prevents (in all but rare cases) ovulation. The risk for severe OHSS is correlated (roughly) to the number and size of the ovarian follicles (on ultrasound) and the serum estradiol concentrations (in the monitored bloodwork). Therefore, cycle monitoring is absolutely essential during controlled ovarian hyperstimulation with menotropins.

(3) premature LH surge

* A premature LH surge (trigger to ovulate) may occur during menotropin therapy. There is apparently a substance (not yet identified) that inhibits ovulation during the maturation of eggs using menotropins. In a natural cycle, the signal from the brain to the ovary to trigger ovulation (the LH surge) appears to occur once the serum estradiol level reaches a certain concentration (about 250 pg/ml) for a certain length of time (about 2 days). In a cycle using menotropins, the serum estradiol level may be greater than 250 pg/ml for much longer than a week without triggering ovulation. Therefore, the existence of a natural "ovulation inhibitor" has been postulated. In possibly 5-20% (1 in 20 to 1 in 5) of women undergoing menotropin therapy there may be a premature LH surge. If this occurs, the use of a GnRH agonist such as Lupron or Synarel may prevent ovulation in future cycles. These medications suppress the ovaries so that higher dosages of menotropins are usually required to accomplish multiple follicular development.

(4) suboptimal development of mature eggs

* Irregular or limited development of follicles can occur on menotropins. At the onset of a menstrual flow follicles prepared for the cycle have begun to develop (FSH normally rises a few days prior to the onset of menstrual flow). In some cycles of COH only 1 or 2 eggs mature. In these cycles, the FSH is apparently taken up by one or two follicles that have developed enough FSH receptors and blood supply to "outcompete" the other follicles for FSH. This is an expensive and disappointing way of developing 1 mature egg since most women using the medication mature one egg per cycle on their own. GnRH agonists (such as Lupron and Synarel) suppress ovarian follicular development so that when started about 1 week prior to the expected menstrual flow they "even out" follicle development at the onset of the upcoming cycle. This improves the chance for multiple egg maturation if the patient has a history of irregular egg development on menotropins.

(5) ovarian torsion

* ovarian torsion is the twisting of an ovary on its ligamentous supports. The ovary is essentially tethered between the uterus and the pelvic sidewall by the uteroovarian ligament (between the uterus and ovary) and the infundibulopelvic ligament (between the ovary and the pelvic sidewall). If the ovary becomes very large and irregular, there is an increased chance that the ovary will twist on these supporting structures. These ligaments that hold the ovary in place also contain the blood supply to the ovary, so if they twist there can be both a great deal of discomfort as well as an interruption in the ovarian blood supply. The torsed ovary can become necrotic ("dead") in which case it will usually need to be removed. Fortunately, ovarian torsion with COH is uncommon.

(6) ovarian cancer

* a serious potential complication of these ovulation promoting medications is ovarian cancer. Overall, about 1 in 70 women in the USA develop ovarian cancer in their lifetime, with widely recognized risk factors for ovarian cancer including low parity, decreased fertility and delayed childbearing. It is also known that oral contraceptive pills decrease the incidence of epithelial types of ovarian cancers, presumably as a result of inhibition of ovulation. This epidemiological information has led to the theory that "the more a woman ovulates the greater her chance for developing ovarian cancer." Unfortunately, there is almost no appropriate information available to either support or reject this theory. The follow up theory as it relates to fertility medications is that "fertility medication that causes the maturation and release of more than one egg in a month may enhance the chances of developing ovarian cancer." Again, no adequate information is available to either accept or reject this theory.

* Concern with an association between ovulation and ovarian cancer is not new.

* As early as 1971 it was proposed that each ovulation results in a small area of trauma at the ovulation site that is then repaired. A disruption in the repair process may somehow result in an abnormal and uncontrolled growth of this tissue (cancer).

* In 1978, it was noted that the inclusion cysts that are occasionally found in epithelial ovarian cancers resemble the inclusion cysts that result from some ovulation and repair cycles, and the theory was proposed that the inclusion cysts in some way cause epithelial ovarian cancers. Since the 1970s, the thought has persisted that fertility drugs enhancing the number of ovulations (albeit generally a small increase in comparison to the total number of ovulations in a typical reproductive lifespan) may also increase the chance for an accident in the repair process that results in ovarian cancer.

* Articles published on these concerns have been widely publicized by the mass media. Unfortunately, the information collected in the published reports does not allow a firm position on the issue of a relationship between fertility drugs and ovarian cancer.

* One widely publicized article from 1992 (A.S. Whittemore and colleagues) reviewed the data from 12 case control studies and suggested that the risk of developing ovarian cancer is increased in women who have used "fertility drugs." The risk was greatest in women who had never been pregnant. On critical review of this study, it is seen that detailed information on fertility drugs was only available in 3 of the 12 studies (leaving a total number of 96 infertile women with cancer compared to a control group of only 135 infertile women) and the particular fertility drugs used by these women was not identified. Perhaps the most important criticism of this study regards the ages of the cancer patients in comparison to the dates that the cancers were diagnosed. The average age at diagnosis was 53 and the time of diagnosis was 1977-1981, meaning that if it is assumed that the women were 30-40 at the time of fertility medication treatment then the actual years of treatment were between 1954 and 1967. Clomiphene citrate was not FDA approved until 1967, menotropins until 1969 and bromocriptine until 1978, so that it appears impossible that these were the drugs referred to in the reviewed articles.

* The National Cancer Institute of the The National Institutes of Health issued a call for abstracts ("RFP NCI-CP-40513-21" 1993) to study the association between ovarian cancers and "fertility evaluation and treatment" soon after this publication, and suggested that given the relative rarity of the disease (1 in 70 in the USA) a reasonable study of relative risk would need to include 10,000 women. This is a far greater number of subjects and total amount of exposure than is contained in any study to date.

* A second widely publicized article from 1994 (M.A. Rossing and colleagues) compared a cohort of 3800 plus women evaluated for infertility between 1974 and 1985 in Seattle and found that there were 11 ovarian cancers among these women as compared to an expected number of 4.4. The 11 cancers consisted of 5 borderline tumors, 4 invasive epithelial cancers, and 2 granulosa cell tumors. Of the 11 women developing cancer, 9 had used clomiphene citrate. Comparisons of cancer developing in infertile clomiphene users to infertile women who had not used clomiphene demonstrated no significant difference in the clomiphene group. However, when infertile women who used clomiphene for 12 or more months was compared to the control group, an increased risk was identified. Oddly, the risk for clomiphene users if 12 or more cycles was greater in gravid women than in nulligravid women, since gravity is known to be protective. Also, most cause and effect relationships have a dose dependent increase in outcome, such that the risk of cancer should be directly proportional to the amount of clomiphene used. In this study, there was a mild protective effect if up to 11 cycles of clomiphene was used and then suddenly there was an increase in the risk when 12 cycles were used. The number of cases in this study is also quite small, with only 5 cases of cancer being considered when looking at infertile women with 12 or more cycles of clomiphene use.

* In 1995 an Australian group followed 10,000 plus IVF patients, about 5,000 of whom used ovulation enhancing medications and about 5,000 of whom underwent natural cycle IVF (without menotropins) or did not receive treatment. This group found that the age standardized incidence ratios for ovarian cancer was not statistically different between those who used fertility medication and those who did not. This group did identify a significant increase in risk for ovarian cancers in couples with "unexplained infertility" as compared to the infertile controls. Unfortunately, the follow-up period for this important study was only 5-10 years.

The potential association between fertility drug use and ovarian cancer is quite important. Hopefully, there will continue to be interest in this field over the next several years. Unfortunately, there is not enough information at this time to firmly express an opinion based on fact. One interesting observation of my own is that at national meetings this subject is occasionally approached by very conservative and elderly infertility specialists who all seemingly recount that their own extensive experience with fertility drugs does not suggest an association with ovarian cancers.


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Eric Daiter, M.D. - Edison, NJ - E-Mail: - Phone: (908)226-0250

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