Sympathetic neural hyperalgesia edema syndrome as a cause of autoimmune hearing loss.

PURPOSE: To describe another previous unreported manifestation of the sympathetic neural hyperalgesia edema syndrome - autoimmune hearing loss. MATERIALS AND METHODS: Dextroamphetamine sulfate 30 mg extended release capsules was given to a woman to try to help her conceive since, with her pelvic pain, chronic fatigue syndrome, and diarrhea, it was thought that an inflammatory condition related to permeation of unwanted chemicals into endometrial tissue related to the sympathetic neural hyperalgesia edema syndrome could be inhibiting her failure from conceiving despite three cycles of embryo transfer. RESULTS: Not only did the symptoms mentioned above disappear, but she also noted marked improvement of hearing loss that had been present for several years. The improvement in hearing was documented by audiology tests and had not responded to many months of 15 mg/day prednisone. CONCLUSIONS: Autoimmune hearing loss (diagnosis established by her ear nose and throat specialist) should be added to the long list of manifestation of the sympathetic neural hyperalgesia edema syndrome.

Influence of the conclusion of a recent large cooperative study in changing standard protocol of inducing menses in anovulatory women with oligomenorrhea prior to initiating ovulation induction with anti-estrogens and outcome.

PURPOSE: To compare pregnancy rates following ovulation induction in anovulatory women with clomiphene citrate vs. letrozole and to determine the relative confounding effect of inducing menses or not. The study also evaluated whether starting these anti-estrogen drugs later in the menstrual cycle has-less adverse effect on endometrial thickness. MATERIALS AND METHODS: Prospective series with choice by physician of inducing menses or not or choosing clomiphene citrate or letrozole for ovulation induction. Peak endometrial thickness was compared between drugs and between those conceiving or not. RESULTS: There were 21 first cycles using letrozole and 42 using clomiphene. Menses were not induced in 18/21 (86%) letrozole cycles and 24/42 (57%) clomiphene cycles. Clinical pregnancies occurred in four (22.2%) letrozole cycles without induced menses with one miscarriage vs. 4/24 (16.6%) clomiphene cycles, no mis- carriage. One of three (33.3%) letrozole cycles with menses induced achieved a clinical pregnancy vs. only 1/18 (5.5%) of clomiphene cycles. There were no miscarriages. CONCLUSIONS: Though the endometrial thickness was higher with clomiphene without induced menses vs. menses induced (11 mm vs. 9.5 mm), one cannot explain the trend for lower pregnancy rates in women with induced menses because of thinner endometria since the thickness was 10.3 mm for clomiphene and 10.0 with letrozole.

The correlation of the degree of abnormal sperm morphology using strict criteria and pregnancy rates following intrauterine insemination (IUI).

OBJECTIVE: To determine the effect of extremely low sperm morphology on pregnancy rates following intrauterine insemination (IUI) where all other semen parameters were normal. MATERIALS AND METHODS: Retrospective review of all IUI cycles over a two-year period on infertile women age ≤ 35 where all parameters, but morphology had to be normal. The data were evaluated according to seven levels of percentage of normal morphology (NM): 0, 1, 2, 3, 4, 5, and ≥ 6%. RESULTS: The percent live delivery was 9.5, 16.7, 8.8, 16.1, 11.4, 12.3, and 10.9%. CONCLUSIONS: Morphology of 0% or 1% did not seem to impair pregnancy rates following IUI. More studies are needed but should include determining the confounding effect of the type of morphologic abnormality.

A normal baby is possible despite twins following a single embryo transfer even if one twin is genetically defective.

PURPOSE: To demonstrate that it is important to consider all possibilities when confronted with a decision to terminate a pregnancy because it is likely to be chromosomally abnormal. MATERIALS AND METHODS: A cell free DNA test was performed on a woman with dichorionic diamniotic twins that followed the transfer of a single embryo. RESULTS: The cell free DNA test was consistent with trisomy 21. Two perinatologists favored identical twins and thus suggested termination since both twins would be trisomy 21 and the couple did not want to raise a child with Down's syndrome. Our group suggested the possibility that these were fraternal twins with one occurring from natural conception. We suggested to forego termination by D&E but to undergo an amniocentesis at 16 weeks. One twin had obvious cardiac abnormalities by ultrasound and this one was reduced while amniocentesis with karyotype was performed on fetus 2. The results showed a normal male. CONCLUSIONS: One should consider all possibilities before suggesting termination of a very desired pregnancy. This woman had also been advised by other specialists in reproductive endocrinology that conception with her own oocytes (as did occur here) was not possible and she should consider donor oocytes based on her marked diminished oocyte reserve.

Serum levels of the immunomodulatory protein, the progesterone induced blocking factor (PIBF) which is found in high levels during pregnancy is not higher in women with progesterone (P) receptor (R) positive vs. negative breast cancer.

PURPOSE: To determine if serum levels of the immunomodulatory protein, the progesterone induced blocking factor (PIBF), which is present in high levels during normal pregnancy, is present in higher levels in women with breast cancer positive for progesterone receptors. The study would also determine whether the presence or absence of the estrogen receptor in any way modifies PIBF expression. MATERIALS AND METHODS: PIBF using a research ELISA was evaluated in the follicular phase in 21 women with receptor status as follows: seven with estrogen receptor (ER)+ and progesterone receptor (PR)+, seven with ER- and PR+, and seven with ER+ and PR. RESULTS: The results showed no differences in serum PIBF in the three groups. The serum PIBF levels were no different than historical controls in the follicular phase. CONCLUSIONS: Measurement of serum PIBF does not seem to be an important marker to use to either detect women with breast cancer or to help determine tumor virulence or potential specific therapies. If PIBF plays a role in helping cancer cells to escape immune surveillance, it seems that the intracytoplasmic PIBF would be the form most likely operative.

Dextroamphetamine sulfate provided quick relief of severe post-partum depression that was recalcitrant to standard antidepressants and psychotherapy.

PURPOSE: To determine if dextroamphetamine sulfate could improve symptoms of post-partum depression. MATERIALS AND METHODS: A woman with severe post-partum depression that was resistant to standard antidepressant therapy and psychotherapy was treated with dextroamphetamine sulfate extended release capsules 15 mg/day. RESULTS: A quick and complete abrogation of the depression ensued along with improvement of migraine headaches, insomnia, and chronic fatigue. CONCLUSIONS: Dextr6amphetamine sulfate should be considered as a treatment modality for post-partum depression.

Sperm with an abnormal hypo-osmotic swelling test--normal fertilization, normal embryo development, but implantation failure.

PURPOSE: To review the clinical importance of including the hypo-osmotic swelling (HOS) test in routine male fertility testing which in general is not evaluated by most physicians dealing with infertility. MATERIALS AND METHODS: Pregnancy rates were evaluated in patients with low HOS test scores. A low HOS test was specifically defined as having less than 50% of sperm exhibiting the normal physiologic response of tail swelling, when subjected to a hypo-osmolar solution. Pregnancy rates of patients with low HOS test were examined after intercourse, intrauterine insemination (IUI), conventional oocyte insemination, and in vitro fertilization (IVF). Patients with a low HOS test were also treated with a protein digestive enzyme chymotrypsin. Patients receiving intervention then underwent IUI, IVF with conventional oocyte insemination, or IVF with intracytoplasmic sperm injection (ICSI). Pregnancy rates of the cohort receiving intervention were then examined for comparison. RESULTS: The HOS test abnormality leads to normal fertilization but almost invariably negatively effects embryo implantation. Treatment with chymotrypsin, or performing IVF with ICSI, can overcome the toxic protein causing the embryo implantation defect. This toxic protein may be cryolabile and freezing sperm or embryos may prove to be another mode of therapy. CONCLUSIONS: The HOS abnormality may be the most reliable semen abnormality predicting failure to conceive even with IVF unless the defect is negated. Therapy is very effective. Unfortunately this test is rarely evaluated by most infertility specialists but it should be. The frequency increases with age.

Efficacy of a single injection of human chorionic gonadotropin at peak follicular maturation in natural cycles on pregnancy rate and mid-luteal hormonal and sonographic parameters.

PURPOSE: To discover if infertile women with presumed luteal phase deficiency would improve pregnancy rates, mid-luteal sera estradiol (E2) and progesterone (P), and increase the percentage of women achieving a mid-luteal sonographic homogeneous hyperechogenic endometrial texture by the addition of a single injection of human chorionic gonadotropin (hCG). MATERIALS AND METHODS: Women with over one year of infertility with regular menses and with no other known infertility factor were presumed to have the need for extra P in the luteal phase based on previous studies. Women aged ≥ 30 years were selected along with women < 30 years who had pelvic pain or dysmenorrhea. Women aged 40-45 were evaluated separately. They were treated with either vaginal micronized P 8% twice daily alone or 10,000 units of hCG at the time of peak follicular maturation was also given. Women were eliminated if they did not achieve an 18-24 average diameter follicle with a serum E2 of > 200 pg/ml. Seven days after ovulation, sera E2 and P were measured along with endometrial thickness and echo patterns. RESULTS: The only significant difference between groups was an increased mid-luteal serum E2 in the group receiving additional hCG. However, this did not result in an increased pregnancy rate. CONCLUSIONS: In general, adding a single injection of hCG to P luteal support does not improve pregnancy rates in natural cycles where women were treated with supplemental P.

A prospective comparison of outcome following cryopreservation using vitrification vs. a modified slow-freeze protocol of 2 pronuclear (2PN) and day 3 multi-cell embryos.

PURPOSE: To compare the efficacy of vitrification of 2 pronuclear and day 3 cleavage stage embryo vs. a modified slow freeze protocol that historically has achieved good survival and pregnancy rates at these stages. MATERIALS AND METHODS: Embryos were randomly assigned by day to freezing at the 2 proncular stage or day 3 cleavage stage embryos by either vitrification or a modified slow freeze protocol. Comparisons were made for survival rate, cleaveage rate, and pregnancy rate. RESULTS: The results were comparable with a slight edge to vitrification. Only the implantation rates of day 3 cleavage staged embryos (75% vs. 30.4%) showed a significant difference. CONCLUSIONS: Vitrification seems to be equally or possibly slightly superior to freezing embryos at the 2 pronuclear or day 3 cleavage stage vs. a modified slow freeze protocol that had been previously found to be superior to the slow freeze method of LaSalle-Testart.

Failure to increase the thickness of thin endometria with intrauterine infusion of granulocyte colony stimulating factor (G-CSF).

PURPOSE: To corroborate or refute a previous study suggesting that intrauterine infusion of granulocyte colony stimulating factor (G-CSF) could significantly improve endometrial thickness into more fertile levels when the endometrial thickness was ≤ five mm. MATERIALS AND METHODS: Three women whose endometrial thickness never exceeded five mm on the in vitro fertilization-embryo transfer (IVF-ET) cycle or subsequent attempted frozen ETs using graduated estradiol had intrauterine infusion of G-CSF to the estradiol regimen. RESULTS: Not one of the three women improved the endometrial thickness beyond five mm and none conceived on the G-CSF cycle. One woman had a subsequent pregnancy following a frozen ET with only a four-mm thickness with no infusion of G-CSF. CONCLUSIONS: These data do not confirm the efficacy of intrauterine infusion of G-CSF for poor endometrial thickness. Perhaps only certain cases will respond. A larger series could take time to accumulate since other studies have shown that only 0.3% of women with ≤ five mm endometrial thickness in the late proliferative phase during an IVF-ET cycle will not improve the endometrial thickness > five mm using graduated estradiol protocols.

Mid-luteal phase injection of subcutaneous leuprolide acetate improves live delivered pregnancy and implantation rates in younger women undergoing in vitro fertilization-embryo transfer (IVF-ET).

PURPOSE: To determine if a single injection of one-mg leuprolide acetate three days after embryo transfer (ET) in younger women causes an increase in pregnancy rates, and if so, is it associated with a higher initial serum hCG level? MATERIALS AND METHODS: A prospective study was initiated where women aged ≤ 35 years were offered the option of taking the leuprolide or not. RESULTS: Though a significant difference was not found, there was a trend for higher live delivered pregnancy rates in those taking the leuprolide supplement (47.8%) vs. those not taking it (38.6%). There was no difference in the first serum beta hCG level. CONCLUSIONS: The trends is interesting enough to continue with a higher powered study.

Correlation of ImmunoBead® and ImmunoSphere™ Immunoglobulin G (IGG) tests on detecting antisperm antibody (ASA) on sperm.

PURPOSE: To determine the correlation with detection of antibody on sperm by a new ImmunoSphere™ Immunoglobulin test vs. ImmunoBeads®. MATERIALS AND METHODS: A sampling of sperm tested for antisperm antibody (ASA) tested by direct Immunobead? assay with levels varying from zero to 100% were compared to the percentage of sperm positive for ASA by a new test using immunospheres. RESULTS: The correlation was not perfect but, in general, there was good correlation. CONCLUSION: Now that the manufacturer is curtailing the manufacture of immunobeads, it is comforting to see a good correlation with immunospheres.

The use of granulocyte colony stimulating factor to enhance oocyte release in women with the luteinized unruptured follicle syndrome.

PURPOSE: To determine if an injection of granulocyte colony stimulating factor (G-CSF) prevoulatory can enable oocyte release from the follicle in women who have failed to release in natural cycles despite an endogenous luteinizing hormone (LH) surge, and also despite treatment with human chorionic gonadotropin (hCG) or a gonadotropin releasing hormone agonist (GnRHa). MATERIALS AND METHODS: A single injection of 100 mg G-CSF was given in the late follicular phase followed by hCG 10,000 units at peak follicular maturation in women with at least three consecutive cycles of luteinization without oocyte release. RESULTS: Six women had ten cycles with G-CSF and hCG. Definite release occurred in four, inconclusive in four, and definitely the luteinized unruptured follicle in two. Biochemical pregnancies occurred in two of the cycles where oocyte release occurred and a live delivered pregnancy in another cycle of release. CONCLUSIONS: Without controls one cannot state with certainty that G-CSF enabled oocyte release when hCG and leuprolide failed. Nevertheless, the data do support a trial with G-CSF before proceeding to IVF-ET.

In vitro fertilization (IVF) outcome in women in overt menopause attempting to induce follicular maturation by follicle stimulating hormone (FSH) receptor down-regulation.

PURPOSE: To determine the frequency of ovulation induction, obtaining oocytes leading to embryos, and pregnancy rates per embryo transfer in women with premature menopause. MATERIALS AND METHODS: Prospective observational study of women hoping to have in vitro fertilization-embryo transfer (IVF-ET) with their own oocytes despite being in menopause. Ethinyl estradiol was used to lower follicle stimulation hormone (FSH) and restore sensitivity of follicles to mild FSH stimulation. RESULTS: Three of five women had a live baby. Only one woman failed to induce ovulation and thus failed to have an embryo to transfer. One woman conceived two times and delivered a live healthy baby twice. The live delivered pregnancy rate per transfer was 20% (4/20) with generally one or occasionally two embryos transferred. The pregnancy rate per retrieval was 9.3% (4/43). CONCLUSIONS: These data can help other women in this circumstance to decide on IVF with their own eggs or switch to donor eggs.

Failed fertilization with conventional oocyte insemination can be overcome with the ability of ICSI according to binding or failing to bind to the zona pellucida.

PURPOSE: To determine the frequency of failed fertilization with conventional oocyte insemination and to determine the ability of intracytoplasmic sperm injection (ICSI) to overcome the failed fertilization according to binding or failing to bind to the zona pellucida. MATERIALS AND METHODS: Retrospective review of 12,448 in vitro fertilization (IVF) cycle to identify cycles where failed fertilization occurred following conventional oocyte insemination with seemingly normal sperm. A number of three oocytes retrieved was required. RESULTS: There were only 12 cases of failed fertilization (0.1%). Six were related to failure of any or few sperm attaching to the zona pellucida These six had high fertilization rates with ICSI. Six had normal attachment and five attempted another cycle, this time with ICSI. Only 60% had good fertilization. CONCLUSIONS: When there is failed fertilization with normal sperm oocyte binding following conventional oocyte insemination, ICSI may still be effective in 60% of the cases, but it would be probably recommended to combine ICSI with artificial oocyte activation by calcium ionophore.

The effect of clomiphene citrate vs. letrozole on post-coital tests.

PURPOSE: To determine if letrozole is less likely to create a hostile cervical mucus than clomiphene citrate. MATERIALS AND METHODS: Post-coital testing compared at time of peak follicular maturation in women attaining mature follicles in first or second cycle of these two drugs. The study was randomized. Intercourse occurred at least 8-16 hours before. RESULTS: Poor post-coital tests were found in twice the frequency in letrozole cycles than clomiphene citrate cycles. CONCLUSIONS: Despite its shorter half-life, letrozole seems to be as least as likely, if not more, to adversely affect cervical mucus.

The progesterone receptor antagonist mifepristone does not lower serum progesterone induced blocking factor (PIBF) in the presence of progesterone.

PURPOSE: To determine if mifepristone can lower serum levels of a progesterone (P) induced immunomodulatory protein believed to be needed for the fetus to escape immune surveillance. MATERIALS AND METHODS: A female volunteer had her serum P induced blocking factor (PIBF) increased by ingestion of oral micronized P. While remaining on P mifepristone, 200 mg/day was given for six days when another serum PIBF level was obtained. RESULTS: The serum PIBF was 273 ng/ml after five days of oral micronized P. It increased further to 737 ng/ml despite taking six days of 200 mg mifepristone. CONCLUSIONS: The mechanism for inducing abortion by mifepristone does not seem to be related to decreasing serum levels of PIBF. This does not eliminate the possibility that the mechanism involves reducing the intracytoplasmic PIBF levels.

Intravenous intralipid therapy is not beneficial in having a live delivery in women aged 40-42 years with a previous history of miscarriage or failure to conceive despite embryo transfer undergoing in vitro fertilization-embryo transfer.

PURPOSE: To evaluate the efficacy of intralipid intravenous infusion in achieving a live pregnancy following IVF--embryo transfer in women of advanced reproductive age (40-42 years). MATERIALS AND METHODS: A matched control was performed. Women aged 40-42 with a previous history of miscarriage or who failed to conceive despite previous embryo transfer who entered an IVF program were offered intravenous intralipid therapy (four ml of 20% liposyn II in 100 ml normal saline over one hour) during the mid-follicular phase. Clinical pregnancy rates (eight weeks with viable gestation) and live delivered pregnancy rates were then determined and compared. RESULTS: The results were evaluated after ten matched cycles. There were no clinical pregnancies in those receiving intralipid vs. a 40% clinical and a 30% live delivered pregnancy rate in the untreated controls (p = 0.087, Fisher's exact test). The study was terminated because of these preliminary data. CONCLUSIONS: In the test tube, adding intralipid to natural killer cells can inhibit their cytolytic action. However, the use of intravenous intralipid to suppress natural killer cell activity does not seem to improve the chance of a live delivery in women aged 40-42 years with a previous history of miscarriage. In fact this therapy may actually be detrimental in this age group. Since efficacy of this therapy was not found in a group of advanced reproductive age, it is not clear why this should be effective for a younger population. A controlled study for the younger group is needed. Perhaps such a study could be limited to only those with miscarriage rather than also concluding failure to conceive despite embryo transfer. Intralipid failed to improve live delivered pregnancy rates in women with prior miscarriage or previous failure with embryo transfer.

Chronic unremitting lower abdominal pain quickly abrogated following treatment with amphetamine.

PURPOSE: To describe a cause and treatment for chronic unremitting lower abdominal pain of long duration with unknown origin. MATERIALS AND METHODS: A 50-year-old woman with 30 years of unexplained right lower quadrant pain was treated with dextroamphetamine sulfate. RESULTS: Dramatic complete abrogation of the pain occurred within two weeks. The complete relief persisted for two years while she remains on therapy. CONCLUSIONS: Symphathetic neural hyperalgesia edema syndrome should be considered whenever there is refractory pelvic or abdominal pain.

Increased tissue permeability and sympathetic nervous system hypofunction may be the common link between dysmenorrhea, chronic pelvic pain, Mittelschmerz, and Crohn's disease.

PURPOSE: To determine if severe periovulatory diarrhea in a woman with Crohn's disease for just one day may be related to increased permeability of the large bowel related to hormonal changes that occur at this time of menstrual cycle. MATERIALS AND METHODS: Dextroamphetamine sulfate was given to a woman whose Crohn's disease was markedly improved by adalimumab but who still had one day of severe diarrhea at mid-cycle. RESULTS: She did not have any diarrhea or frequent defecation for the first two periovulatory times before she achieved pregnancy. Previously for two years there had not been one month where she did not have the severe periovulatory diarrhea. CONCLUSIONS: This case helps support the concept that the classic symptoms of Mittelschmerz in women with endometriosis may be related to periovulatory events which either cause increased permeability of an already compromised tissue, whether it be pelvic or bowel or other tissues, or these periovulatory events impair sympathetic nervous system function, which is already impaired.