Organ donation after cardiac death in the Middle East.

INTRODUCTION: The shortage of organ donors along with the increased number of waiting recipients have created the need for new strategies to expand the organ pool: living donors, split livers, domino livers, and organs from donations after cardiac death (DCD). The purpose of this article was to focus upon aspects of DCD application in the religious, traditional, ethical, and legal aspects of the Arab world. BACKGROUND: DCD can increase the donor pool by 15%-25%. Several ethical, legal, and social concerns need to be addressed to make DCD more widely accepted by the general population in Western countries as well as in the Middle East. Organs from DCD donors have been transplanted since the 1960s. As soon as brain death criteria were published in 1968, organ retrieval from cadaveric heart-beating donors predominated. Donation after brain death (DBD) almost completely replaced DCD. In the 1990s, the organ shortage led to DCD in many countries, but not in the Arab world. DCD is still not accepted by most in the Arab world due to religious, ethical, social, and legal issues. CONCLUSION: DCD in the Arab world is more complicated than in Western countries. It should be re-evaluated and thoroughly reviewed with the new criteria for DCD and its implementation in our region.

Effect of age and cycle responsiveness in patients undergoing intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the effects of age and number of embryos available for transfer on pregnancy rate (PR) in couples undergoing intracytoplasmic sperm injection (ICSI). DESIGN: Retrospective study of patients undergoing ICSI for male factor infertility. SETTING: Tertiary care academic center. PATIENT(S): One hundred twelve patients < 37 years of age and 57 patients > or = 37 years of age who underwent ICSI with uterine ET or tubal ET. INTERVENTION: Compare cycles in which three embryos or fewer were available for transfer with those with four or more available embryos. MAIN OUTCOME MEASURE(S): Implantation, embryo availability, and pregnancy and miscarriage rates. RESULT(S): Younger patients did significantly better with regard to PR (47% versus 26%), implantation rate (11.4% versus 6.6%), and ongoing PR (40% versus 19%). Patients in whom more than four embryos were transferred also did better than patients in whom three or fewer embryos were available for transfer, with an implantation rate of 14.2% versus 4.2%. In women < 37 years of age, 85% of cycles produced more than three embryos, versus 61% in women > or = 37 years of age. When cycles yielding three embryos or fewer were excluded, the younger group tended to do better, with an ongoing PR of 48% versus 33% for the older group, but the differences were not statistically significant. Both groups had similar number of embryos transferred per cycle. CONCLUSION(S): Age affects cycle responsiveness, and the number of embryos available for transfer affects fertility in patients undergoing ICSI. Older women with good ovarian response, producing more than three embryos suitable for transfer, have a PR similar to younger patients. Cycles yielding three embryos or fewer have a poor prognosis.

Artificial hormonal replacement cycles have no advantage over hyperstimulated cycles in a gamete intrafallopian transfer oocyte donation program.

OBJECTIVE: To evaluate if the previously reported increased implantation rates in hormonally replaced egg donation cycles relative to hyperstimulated IVF-ET cycles apply when GIFT is used. The increased implantation rates in the recipients have been attributed to the absence of the negative effects of hyperstimulation on endometrial receptivity. DESIGN: A prospective comparison of implantation rates in hyperstimulated and hormonally replaced cycles when GIFT was used in both the egg donors and their corresponding recipients. PATIENTS: Excess mature oocytes from 35 women undergoing GIFT after controlled ovarian hyperstimulation (COH) were transferred into the fallopian tubes of 35 hormonally replaced women. RESULTS: The male partners of all donors and recipients had normal semen parameters. The two groups did not differ significantly in the mean age, duration of infertility, and quality of eggs transferred. There was no statistically significant difference in the mean number of oocytes transferred per cycle between the donors and the recipients. The mean implantation rate per mature oocyte transferred was significantly higher in the donors (19.3%) than in the recipients (6.6%). CONCLUSION: Our results with GIFT show higher implantation rates in hyperstimulated cycles than in hormonally replaced cycles. These results differ from those reported in IVF-ET that suggest an adverse effect of COH on implantation rates.

Subtle tubal abnormalities adversely affect gamete intrafallopian transfer outcome in women with endometriosis.

OBJECTIVES: To evaluate prospectively the impact of subtle tubal disorders on GIFT pregnancy rates in women with pelvic endometriosis. DESIGN: A prospective comparison of pregnancy rates in different stages of endometriosis while controlling for the presence of tubal abnormalities. INTERVENTIONS: A total of 146 patients with endometriosis underwent 201 GIFT procedures. During laparoscopy special attention was brought to the fallopian tubes and any anatomical disorders were recorded. Tubal abnormalities included tubal sacculations, diverticulae, convolutions, phimosis, fimbrial agglutination, and peritubal adhesions. Best tube was considered in the final analysis. RESULTS: The presence of tubal abnormalities significantly lowered the pregnancy rates in all stages of endometriosis. When we controlled for age, semen characteristics, number of mature oocytes transferred, and tubal status, the extent of anatomical tubal disorders was the most important prognostic factor in determining pregnancy outcome. CONCLUSION: The extent of tubal abnormalities rather than the stage of endometriosis seems to be an important prognostic factor in determining GIFT pregnancy rates. Couples should be counseled accordingly and accurate prognostic parameters should be explained before enrollment in a GIFT program.

Ovarian cyst aspiration: a therapeutic approach to ovarian hyperstimulation syndrome.

Ultrasonographically guided transvaginal aspiration of ovarian cysts in women with severe OHSS after GIFT or IVF was safe and has resulted in immediate relief of symptoms, a shorter disease process, and outpatient treatment. The patients were allowed to go back to normal activity after the procedure. The progression of the disease was interrupted and six of seven patients carried beyond 20 weeks' gestation.

Improved pregnancy rates and outcome with gamete intrafallopian transfer when follicular fluid is used as a sperm capacitation and gamete transfer medium.

Follicular fluid (FF) is a dynamic medium rich in steroids, polypeptide hormones, and growth factors. Preovulatory FF can stimulate spermatozoal acrosome reaction. Moreover short preincubation of washed sperm with FF improves sperm performance in the hamster egg penetration assay. In the current study, FF was used to capacitate sperm and as a transfer medium in 131 gamete intrafallopian transfer (GIFT) procedures. Ham's F-10 medium (GIBCO, Grand Island, NY) with 50% maternal serum was used in another 29 GIFT procedures. In the Ham's F-10 group, 29 GIFT procedures were performed in 25 patients with a pregnancy rate of 21% per laparoscopy and 24% per patient. In the FF group, 131 GIFT procedures were performed in 100 patients with a pregnancy rate of 50% per laparoscopy and 66% per patient, with a 59% ongoing pregnancy rate per patient. The most significant improvement was in the male factor group with a pregnancy rate of 0% in the Ham's F-10 group and 44% per procedure in the FF group. We conclude that the use of FF for sperm capacitation and as a gamete transfer medium significantly improves GIFT pregnancy rates and outcome.

The role of catecholamines in estradiol and progesterone secretion by cultured explants and cells of human term placentae.

The effects of physiological concentrations of the native catecholamines norepinephrine and epinephrine upon term placental hormonal function were examined by measuring estradiol and progesterone secretion by organ and cell culture systems. Results show that, in explants, both catecholamines caused a significant increase in the secretion of both sex steroids, p less than 0.05. Estradiol secretion was blocked by the alpha and beta adrenergic receptors antagonists, phenoxybenzamine and propranolol, respectively, p less than 0.05. Norepinephrine but not epinephrine dependent progesterone secretion was blocked by propranolol. In cells, epinephrine stimulated cyclic AMP generation and caused a 30% increase in estradiol secretion, p less than 0.05. Both were abrogated by propranolol. Norepinephrine increased secretion by 25%, p less than 0.05. This was inhibited by yohimbin and prazosin, alpha-1 and -2 receptors antagonists, respectively. In conclusion, the placenta in vitro is a target organ for catecholamines. The marked response of the explant system as compared with the marginal response of the cell culture system indicates that cell to cell contact/communication is required for full expression of catecholamine effect.

Chondroitin sulphate. A new intraperitoneal treatment for postoperative adhesion prevention in the rabbit.

A study was designed to test chondroitin sulphate and other high-molecular-weight solutions, using the rabbit uterus as the surgical model, in the prevention of postoperative adhesions. Eighty-five mature white female New Zealand rabbits underwent surgical injury of each uterine horn, with surgical repair of the left horn only in all animals using 9-0 nylon. The rabbits were randomly divided into five groups: groups A, B and C received 25 mL of chondroitin sulphate, sodium carboxymethylcellulose or 32% dextran 70, respectively. The remaining two groups received either 50 mL of normal saline (D) or no solution (E). Postoperatively the animals were killed, and the adhesions were carefully scored. The results clearly demonstrated the superiority of chondroitin sulphate as an intraperitoneal treatment for the prevention of postoperative adhesions (P less than .001 vs. carboxymethyl cellulose, dextran, saline and control).

Interleukin-1: a possible role in the infertility associated with endometriosis.

Increased numbers of activated macrophages are associated with mild endometriosis. Interleukin-1 (IL-1) is a protein produced by macrophages and is believed to be a primary mediator of host responses. IL-1 induces prostaglandin and fibrinogen synthesis and stimulates fibroblast proliferation. This study was undertaken to evaluate the role of IL-1 in the infertility associated with mild endometriosis. Peritoneal fluid (PF) was obtained at laparoscopy from 11 patients with minimal or mild endometriosis and from 7 women undergoing tubal ligation. Peritoneal macrophages were isolated and cultured for 24 hours. Peritoneal and macrophage culture fluids were studied for IL-1 activity, which was measured with the EL-4 assay. IL-1 activity was present in the PF of 10 of the 11 patients with endometriosis and 11 of the 11 macrophage culture fluids and was absent in the PF and macrophage culture fluid of the tubal ligation patients. The effect of recombinant alpha-IL-1 on the in vitro growth of 2-cell mouse embryos was also studied. IL-1 in concentrations similar to those present in the PF (greater than 1 U/ml) was toxic to mouse embryo development. We conclude that the IL-1 may play a role in the infertility associated with endometriosis.

Enhancement of human sperm motility and velocity in vitro: effects of calcium and creatine phosphate.

Because of their roles in motility regulation and energy transport, calcium and creatine phosphate were examined for their effects on sperm motility and velocity in specimens of normal donors. Semen or migrated sperm fractions were incubated with of 1 mmol of calcium, 5 mmol magnesium, and 10 mmol of creatine phosphate (n = 28) or in the presence of 4 mumol of Verapamil, calcium, and creatine phosphate (n = 10). The samples were subjected to multiple exposure photography (four picture frames of two different drops) at 0, 1, 4, or 5 and at 10 hours and sperm motility and velocity were analyzed. In both calcium and calcium-creatine phosphate conditions, sperm motility and velocity were significantly increased, compared with control values (P = between less than 0.001 and 0.05). Sperm motility declined following Verapamil exposure, but the motility values remained at the level of the control in the presence of additional calcium or creatine phosphate. The effects of calcium and creatine phosphate take place rapidly; within 1 minute all improvements in sperm velocity and motility are fully achieved. There is no loading effect of calcium, and when the sperm is transferred into media without the additional calcium, the velocity decreased to that of the initial control value. Magnesium alone had no effect on motility or velocity. These experiments indicate that calcium or creatine phosphate can support sperm motility and velocity at a significantly increased level. Thus the addition of calcium or creatine phosphate to the insemination media may enhance the fertilizing capacity of sperm during in vitro fertilization or gamete intrafallopian transfer procedures.

The role of ACTH in placental steroidogenesis.

We have studied the possible function of the placental adrenocorticotrophic hormone-(ACTH-) like substance (PALS) in placental steroidogenesis by measuring oestradiol (E2) and progesterone (P4) in term human placental explants incubated with commercially available porcine ACTH I-39. There was a dose-dependent increase in the E2 and P4 released into the medium at 24 h as compared to controls. At 48 h, no significant effect was noted. Propranolol (10(-5) M) did not block the effect of ACTH on P4 release. The data suggest that ACTH may have a regulatory role on placental steroidogenesis. The possible mechanisms of action of PALS on the placenta and the adrenal are discussed, and the role of PALS in the maintenance of pregnancy and in maternal response to stress is suggested.

Effect of antihypertensive drugs on catechol-O-methyltransferase and monoamine oxidase activity in human term placental explants.

The effects of therapeutic concentrations of antihypertensive drugs on catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) activities in term placental explants were studied. The enzyme activities were measured in tissue fractions using radioenzymatic techniques. At 6 h the incubation COMT activity increased significantly following exposure to verapamil and hydralazine, while exposure to alpha methyldopa caused a significant suppression of the enzyme. At 24 h exposure to hydralazine significantly suppressed the COMT activity. By 6 h the MAO activity was significantly suppressed by verapamil. MgSO4 and propranolol had no effect on the activities of COMT and MAO at 6 and 24 h. These results suggest that COMT and MAO activities in the placenta can be modulated by antihypertensive drugs and, therefore, these drugs might affect local catechol metabolism.

Endometriosis after tubal ligation.

Twenty-three (27.3%) of 84 patients discharged with the diagnosis of endometriosis had undergone tubal ligation 1-15 years (mean, 5) before this diagnosis was made. Twenty (87%) of the 23 underwent laparotomy because of symptoms consistent with endometriosis. Forty-four percent had stage I disease; 52%, stage II; and 4%, stage III. Endometriosis was the only pathologic finding in 19 women (82.6%). This study demonstrated that endometriosis is not a chance finding in women who have undergone tubal sterilization.

The role of catecholestrogens in placental steroidogenesis.

The effect of the catecholestrogen, 2-hydroxyestrone (2-OHE1), on placental steroidogenesis was studied by incubating 2-OHE1 with placental explants for 24 hours and measuring the output of estradiol (E2) and progesterone (P4). 2-OHE1 stimulated the accumulation of E2 and P4 in the media. This effect was inhibited by the alpha-adrenergic blocker, phenoxybenzamine, and the beta-adrenergic blocker, propranolol. We conclude that 2-OHE1 affects placental steroidogenesis and that this effect could possibly be mediated through adrenergic receptors.