George B. Maroulis

Assisted fertility using electroejaculation in men with spinal cord injury―a review of literature

OBJECTIVE To review the effectiveness of rectal probe electroejaculation in terms of pregnancy in treatment of anejaculatory males due to spinal cord injury. The characteristics of electroejaculates also are examined. DATA IDENTIFICATION All English language studies reporting pregnancies as a result of electroejaculation from men with spinal cord injury and related publications on electroejaculation were identified through MEDLINE search and manual scanning of recent relevant journals. RESULTS Electroejaculation has become an accepted mode of semen procurement in anejaculatory individuals, with a success rate of approximately 60% to 90% varying among different centers. In general these electroejaculates exhibit high sperm counts but low motility and poor sperm function. Retrograde ejaculation is also common. Pregnancies using electroejaculates have been documented since 1975 in the form of case reports and small series. Assisted reproductive technology recently has been used in conjunction with electroejaculation. Although results are encouraging, pregnancy rates, however, cannot be accurately estimated because of the lack of large series in the literature. CONCLUSIONS An increasing number of spinal cord-injured patients desiring fertility can achieve pregnancy through combined use of electroejaculation and assisted reproductive techniques. Larger series are needed to establish an accurate pregnancy rate. Elucidation by further studies on etiology of sperm dysfunction of these individuals may improve their prognosis.

Effects of human chorionic gonadotropin, prostaglandin F2α and protein kinase C activators on the cyclic AMP and inositol phosphate second messenger systems in cultured human granulosa-luteal cells

The effects of human chorionic gonadotropin (hCG) and prostaglandin F2 alpha (PGF2 alpha) on the adenylate cyclase-cAMP and inositol phospholipid-phospholipase C-inositol trisphosphate and diacylglycerol transmembrane signalling systems were evaluated in cultured human granulosa-luteal cells. Granulosa-luteal cells obtained from patients undergoing in vitro fertilization were cultured for 72 h prior to addition of hormones. During the last 24 h of culture granulosa-luteal cells were incubated with [3H]inositol. Neither hCG nor gonadotropin-releasing hormone (GnRH) stimulated the inositol phospholipid-phospholipase C signalling system. PGF2 alpha stimulated increases in inositol mono-, bis-, and trisphosphate accumulation in 30 min incubations. NaF (20 mM) mimicked the stimulatory effect of PGF2 alpha on inositol phosphate accumulation suggesting the involvement of a guanine nucleotide regulatory protein in the activation of phospholipase C. In contrast, hCG but not PGF2 alpha or NaF stimulated cAMP accumulation in 30 min incubations. Simultaneous treatment with hCG and PGF2 alpha did not alter the stimulatory effect of PGF2 alpha on inositol phosphate accumulation but reduced (37%) the stimulatory effect of hCG on cAMP accumulation. The protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA) inhibited the stimulatory effects of hCG (76%) and PGF2 alpha (62%) on cAMP and inositol phosphate accumulation, respectively. Thus, cultures of human granulosa-luteal cells possess multiple transmembrane signalling systems which may be modulated by the activation of protein kinase C.

Prospective randomized study of human menotropin versus a follicular and a luteal phase gonadotropin-releasing hormone analog-human menotropin stimulation protocols for in vitro fertilization * †

OBJECTIVE To determine whether gonadotropin-releasing hormone analogs (GnRH-a) initiated either in the luteal phase or in the early follicular phase immediately preceding menotropin will improve the fertilization, implantation, and pregnancy rates (PR) in all IVF patients, when compared with menotropins alone. DESIGN In a prospective, controlled, randomized study we compared a pure follicle-stimulating hormone (FSH) human menopausal gonadotropin (hMG) protocol (group A = control) (n = 93 cycles) to two protocols in which GnRH-a pretreatment plus pure FSH and/or hMG was used in in vitro fertilization candidates. In group B (n = 64) GnRH-a was initiated during the luteal phase and in group C (n = 35) during the follicular phase. RESULTS We found (1) no differences in fertilization and implantation rates between the three protocols; (2) similar pregnancy rates per transfer when similar number of conceptus were transferred (A = 30%, B = 22%, C = 21%); (3) an increase of the number of oocytes obtained; and (4) a reduction in the cancellation rate with both GnRH-a protocols. CONCLUSIONS These findings suggest that there is no obvious superiority between the two GnRH-a protocols in the dosage schedule used and that the major advantage of GnRH-a over non-GnRH-a protocols is in decreasing the cancellation rate and increasing the number of oocytes and conceptus obtained. The follicular phase GnRH-a protocol required less hMG-pure FSH than the luteal phase GnRH-a protocol.

Electroejaculation and assisted reproductive techniques for anejaculatory infertility

Objective To report our experience with electroejaculation combined with intrauterine inseminations (IUI) and other assisted reproductive technologies. Methods Anejaculatory men desirous of fertility were evaluated in our Assisted Reproductive Program. Between March 1991 and December 1994, 26 men (age 24-48) underwent a total of 84 electroejaculations. Causes of anejaculation included spinal cord injury (n = 23) and retroperitoneal lymph node dissection (n = 3). Female partners were superovulated to improve the pregnancy rate. The success in sperm retrieval and pregnancy rates were determined, and the quality of electroejaculates was evaluated. Results Seventy-seven of 84 (92%) electroejaculations were successful, defined by retrieval of more than 10 × 106 total and more than 106 motile spermatozoa. Mean sperm count was 65 million/mL (range 0-569), but mean motility was only 16% (range 0-66). Mean normal morphology was 27% (range 0–71). Ten couples attempted conception. Fifty cycles of IUIs were performed, resulting in four normal term infants and one spontaneous abortion (pregnancy rate 10% per IUI). One patient failed to conceive with eight cycles of IUIs but became pregnant with in vitro fertilization-embryo transfer with micromanipulation using electroejaculates;she delivered a set of healthy twins. Two couples elected donor sperm insemination after failing to conceive by IUI with electroejaculates; both became pregnant. Conclusion Electroejaculation offers an encouraging pregnancy opportunity for anejaculatory men who otherwise are considered infertile. Marked asthenospermia is observed in electroejaculates, the etiology of which remains obscure. Further studies to elucidate the cause may improve pregnancy rates.

Correlation between semen parameters of electroejaculates and achieving pregnancy by intrauterine insemination.

OBJECTIVE To investigate whether any parameter in the routine semen analysis of electroejaculates is correlated with success in achieving pregnancy by IUI. DESIGN Retrospective observational study. SETTING An Assisted Reproductive Program at a tertiary care university center. PATIENT(S) Twenty-seven anejaculatory men with spinal cord injury (n = 24) or history of retroperitoneal lymph node dissection (n = 3), thirteen of whom attempted conception with their wives. INTERVENTION(S) Anejaculatory men underwent rectal probe electroejaculation and electroejaculates were used for IUI. MAIN OUTCOME MEASURE(S) Statistical correlation of semen parameters between electroejaculates that resulted in pregnancy and those that did not. RESULT(S) Seven pregnancies resulted from 56 IUIs using electroejaculates (pregnancy rate = 12.5% per IUI). The total motile sperm count and percentage of normal morphology were significantly higher in the specimens that resulted in pregnancies than those that did not. However, there was no statistically significant difference observed in pH, sperm concentration, or percentage of motility between the two groups. Swim-up techniques used to process electroejaculates significantly improved the motility of the specimens. No pregnancy occurred beyond the fifth IUI attempt. Repeated electroejaculation and duration of spinal cord injury had no effect on the quality of the ejaculates. CONCLUSION(S) The total motile sperm count and the percentage normal morphology of electroejaculates correlate with success in achieving pregnancy by IUI. Because repeated electroejaculation does not improve quality of ejaculate, the initial semen analysis of electroejaculates is not only useful in counseling couples undergoing such treatment program but should be planned for use as an inseminate.

Laparoscopic removal of mullerian remnants in a woman with congenital absence of the vagina.

Most women with mullerian agenesis do not have cyclic pain and therefore do not require surgery. When surgery is necessary, we recommend a laparoscopic approach as described in this report because of the decreased morbidity and cost compared with laparotomy. Results from this case suggest that outpatient laparoscopic treatment of this condition is safe and effective. Regardless of the surgical approach used, a preoperative IVP is essential to limit the risk of damage to the urinary tract.

A prospective series of unruptured ectopic pregnancies treated by tubal injection with hyperosmolar glucose

Objective To evlauate the safety and efficacy of hyperosmolar glucose injection in select unruptured tubal gestations with hCG levels less than 2500 mIU/mL. Methods In this prospective series, 16 patients with an hCG titer less than 2500 mIU/mL and an unruptured ectopic pregnancy were treated by tubal injection with hyperosmolar (50%) glucose. Hyperosmolar glucose was injucted transabdominally into the antimesenteric site of the tubal pregnancy, using a 20-gauge spinal needle. The main outcome measures evaluated were duration of surgery, success rate, time to resolution, and follow-up tubal patency rates. Results Ninety-four percent (15) of the subjects were treated successfully with a median time to resolution of 24 days (range 5–78). The one treatment failure required methootrexate because of rising hCG titers and worsening pain 4 days after the patient was treated with hperosmolar glucose. The mean (± standard error) duration of surgery was 45 ± 6 minutes. So far, all ten patients undergoing postoperative hysterosalpingograms have demonstrated tubal patency in the treated tube. Conclusion Laparoscopic injection with hyperosmolar glucose is an effective, systemically nontoxic alternative treatment for select unruptured ectopic pregnancies (hCG less than 2500 mIU/mL) that achieves tubal patency rates comparable to other conservative medical and surgical thretments.

Hydrogynecography : a new technique enables vaginal sonography to visualize pelvic adhesions and other pelvic structures

Vaginal ultrasonography, done after the transcervical injection of isotonic saline into the cul-de-sac, is a new technique we named hydrogynecography. This was prospectively used in patients suffering from infertility and pelvic pain. In 84% of patients we were able to identify pelvic adhesions confirmed by laparoscopy. In 16% the procedure provided false-negative results.

Treatment of cornual obstruction by transvaginal cannulation without hysteroscopy or fluoroscopy

A new method for relief of cornual obstruction performed totally in the office is presented. We used the Jansen-Anderson catheter with 0.007-cm guide-wire for relief of the obstruction. Ultrasonography is used for demonstrating the position of the catheter and for tubal patency. Subsequent HSG is used for confirmation of tubal patency.

Alternatives to estrogen replacement therapy.

We have now realized the creation of estrogens that act on certain organs and not on others. This has been accomplished by designing a group of compounds, called selective estrogen receptor modulators (SERM), that influence in different ways the tissues of interest, that is, bone, heart, blood vessels, breast, uterus, vagina, and brain.1 These compounds take advantage of the peculiarities of the estrogen receptor and of the effect their binding has on the estrogen receptor. There are two kinds of estrogen receptors, α (ERα) and β (ERβ). The concentrations of these receptors differ in different parts of the body, and the effectiveness of SERMs depends on (a) how much they are taken up by the various parts of the body and (b) how they bind to the receptors.2 The receptors have an -NH2 (N-terminus), a COOH terminus, a DNA binding domain, and a ligand binding domain. For example, whereas one compound may prevent DNA-receptor interaction, another may prevent or stimulate the ligand binding domain. Once the compounds (ligands) bind on the receptor, they are categorized as type I–IV antiestrogens3: type I prevents receptor-DNA interaction (none known); type II inactivates the receptor (i.e., ICI 164); type III causes a partial agonistic effect (i.e., raloxifene); type IV allows conformation of the receptor so that it can bring transcription on a certain number of estrogen-responsive genes (i.e., tamoxifen). Transcription is activated by transcription-activating factors TAF1 and TAF2. TAF1 is on the NH2 end and TAF2 on the COOH end, which may help create agonistic or antagonistic effects. Raloxifene (a SERM) can stabilize certain receptor interactions exerting positive effects on the R receptor and is considered a type III antiestrogen. On the other hand, a compound such as tamoxifene stabilizes the estrogen receptor and can allow transcription of a certain number of estrogen receptors.4 Raloxifene is a benzothiophene and a very interesting compound, because it exerts agonistic and antagonistic activities. Transcription is activated by two different activating factors, TAF1 and TAF2.