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Seasonal distribution in conceptions achieved by artificial insemination by donor.

The distribution of conceptions after artificial insemination from a donor was studied in 259 conceptions at an artificial insemination clinic and found to be seasonal. Conception was not influenced by the number of donors or patients attending the clinic, the frequency of inseminations, or medical skill. Conception was more common from early winter until early spring (October to March) with a peak in November. As variables such as frequency of intercourse and ovulation were irrelevant in these women and highest sperm counts occur from February to March these results suggested a seasonal variation in the quality of the ovulated egg or endometrial receptivity. The waste of eggs after ovulation (or preimplantation conceptuses) at specific times of the year has implications in the treatment of infertility, particularly for in vitro fertilisation and gamete intrafallopian transfer.

England↗

Identification of cyclo(His-Pro)-like immunoreactivity in human follicular fluid: correlation with steroid and peptide hormones.

OBJECTIVE: The purpose of this study was to evaluate human follicular fluid (FF) for the presence of cyclo(His-Pro)-like immunoreactivity (CHP-LI). After verifying its presence, we quantitated the levels and investigated correlations with other follicular parameters, including hormone levels. METHODS: Follicular fluid was collected from female volunteers undergoing controlled ovarian hyperstimulation. Fluid was collected by follicular puncture, either transvaginally (in vitro fertilization) or laparoscopically (gamete intrafallopian transfer) at the time of oocyte retrieval (N = 137). Follicular size was determined ultrasonographically. Assays for steroid and peptide hormones were determined with commercially available radioimmunoassay kits. CHP-LI was measured using a previously reported assay; parallel dilution curves and column chromatography aided in immunoidentity. RESULTS: The mean FF CHP-LI concentration (13.10 +/- 1.83 nmol/L, N = 137) was greater than the corresponding serum values (9.42 +/- 2.45 nmol/L; N = 21) (P < .05). Large follicles (20 mm or greater; 14.45 +/- 1.74 nmol/L) contained significantly more CHP-LI than either medium follicles (16-19 mm; 11.51 +/- 1.88 nmol/L) or small follicles (15 mm or smaller; 10.83 +/- 2.12 nmol/L) (P < .05). Positive correlations were found between FF CHP-LI values and corresponding FF progesterone and prolactin concentrations (r = 0.67 and 0.62, respectively; P < .05). CONCLUSION: Mean CHP-LI levels in the FF are greater than those in the corresponding serum. We suggest that the neuropeptide may be originating from either peptidase cleavage of precursor peptides or from granulosa cell production.

Adult↗

Ventilatory effects of laparoscopy under epidural anesthesia.

This study evaluates the respiratory effects of laparoscopy under epidural anesthesia in seven female patients (ASA physical status I) scheduled for a gamete intrafallopian transfer procedure. Epidural anesthesia was performed with 15-18 mL of 1.5% plain lidocaine using a catheter inserted at the L3-4 level. The upper level of analgesia to pinprick was measured 20 min after lidocaine injection. Ventilatory measurements and arterial blood gas analyses were performed (a) preoperatively, in the horizontal supine position with a T7-9 level of analgesia; (b) in the 20 degrees Trendelenburg position with a T2-5 level of analgesia; (c) during intraabdominal insufflation of CO2 through the laparoscope; and (d) after CO2 exsufflation by manual compression of the abdomen before removal of the laparoscope while in the horizontal position. On-line measurements of VO2, VCO2, VE, VT, F, and PETCO2 were made using a Beckman metabolic cart, while the patients breathed room air through an anesthetic face mask. No significant changes in the ventilatory variables were observed in the Trendelenburg position. In contrast, CO2 insufflation significantly increased VE (from 9.1 +/- 1.0 L/min to 11.8 +/- 2.6 L/min, mean +/- SD), and F (from 16.9 +/- 1.9 breaths/min to 23.1 +/- 3.3 breaths/min, mean +/- SD), whereas VCO2 remained unchanged. PaCO2 remained constant throughout the study. These results suggest that epidural anesthesia may be a safe alternative to general anesthesia for outpatient laparoscopy, as it is not associated with ventilatory depression.

Adult↗

Leuprorelin. A review of its pharmacology and therapeutic use in prostatic cancer, endometriosis and other sex hormone-related disorders.

Leuprorelin (leuprolide acetate) is a gonadotrophin-releasing hormone (GnRH) analogue used to treat a wide range of sex hormone-related disorders including advanced prostatic cancer, endometriosis and precocious puberty. It acts primarily on the anterior pituitary, inducing a transient early rise in gonadotrophin release. With continued use, leuprorelin causes pituitary desensitisation and/or down-regulation, leading to suppressed circulating levels of gonadotrophins and sex hormones. Clinical trials in men with advanced prostatic cancer demonstrate that leuprorelin (usually monthly depot injections of 3.75 or 7.5 mg) is less likely to cause serious adverse cardiovascular effects than diethylstilbestrol, and has comparable efficacy to bilateral orchiectomy or other GnRH analogues. Therefore, the choice between leuprorelin and orchiectomy may be made on the basis of the patient's treatment preference, along with specific patient characteristics and cost implications. Monthly intramuscular or subcutaneous administration of depot leuprorelin 3.75 mg was superior to placebo, and comparable to oral danazol 800 mg/day or intranasal buserelin 900 micrograms/day, in achieving objective and subjective responses in women with endometriosis. Thus, leuprorelin is an effective alternative to other treatments for women with endometriosis, but the recommended duration of its use in this clinical setting is limited to 6 months because it reduces bone mineral density. In children with central precocious puberty, leuprorelin (usually monthly intramuscular or subcutaneous injections of depot leuprorelin 3.75 to 15mg) decreases mean growth velocity and signs of sexual maturation and increases predicted adult height compared with baseline measurements. Although effects on final adult height are predicted from available data and require confirmation in long term follow-up studies, the absence of effective alternatives to GnRH analogues makes leuprorelin a first-line therapy for children with this rare disease. In women with uterine leiomyomata, monthly intramuscular administration of depot leuprorelin 3.75 mg for 6 months markedly reduces uterine volume and fibroid-related symptoms, but, as with other GnRH analogues, these effects dissipate following discontinuation of the drug. As adjuvant therapy in women undergoing in vitro fertilisation or gamete intrafallopian transfer, leuprorelin (usually 0.5 to 1 mg/day subcutaneously) reduces the risk of cancelled cycles for oocyte retrieval by preventing premature luteinisation. While some studies demonstrate an improvement in intermediate end-points such as increased number of mature oocytes retrieved and embryos available for transfer, a significant effect has not been demonstrated on the rate of live births per stimulated cycle.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Successful treatment of long-term unexplained infertility with gonadotropin-releasing hormone agonist analogue and human menopausal gonadotropin.

Thirty-five couples with long-term unexplained infertility were treated in 98 cycles by giving gonadotropin-releasing hormone analogue, human menopausal gonadotropin and human chorionic gonadotropin for induction of superovulation. Pregnancy occurred in 24 cycles (24.5% per cycle and 68.6% per patient). All patients had been treated previously with clomiphene citrate and human menopausal gonadotropin in 110 cycles in conjunction with artificial insemination, but failed to achieve pregnancy. Pituitary suppression with gonadotropin-releasing hormone analogue followed by ovarian stimulation with human menopausal gonadotropin may correct the subtle abnormalities at the hypothalamic hypophyseal level that could be present in cases of unexplained infertility and it should be tried first for these patients before resorting to in vitro fertilization or gamete intrafallopian transfer.

Adult↗

Does the wash-up and swim-up method of semen preparation play a role in sex selection?

Because of the higher built ratio of boys to girls (1.5 : 1) by in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT) at Tygerberg Hospital, the question arose as to whether the wash-up and swim-up method of semen preparation, used for our IVF procedure, plays a role in sex selection. Semen samples of 20 men were evaluated at different time intervals to determine the percentage of F-body-positive spermatozoa. It was found that the swim-up time affects the relationship between Y- and X-bearing spermatozoa, especially at time intervals of 30 and 45 min, where an optimum percentage of Y-bearing spermatozoa (p = 0.0039 and p = 0.0092, respectively) was found. Sperm obtained at these specific time intervals may influence the outcome of sex by IVF and GIFT in favor of males.

Fertilization in Vitro↗

Murine oocyte cryopreservation: comparison between fertilization success rates of fresh and frozen metaphase I and II oocytes.

The surplus of oocytes obtained during in vitro and gamete intrafallopian transfer creates the need to either (1) cryopreserve (196 degrees C) or (2) fertilize these surplus oocytes and then freeze the resulting embryos. During this pilot study, C57BL6 X CBA female mice (F1 generation) were superovulated by means of hormone stimulation, resulting in adequate numbers of murine oocytes. Oocytes thus obtained were classified according to their nuclear status. The maturation stage of oocytes was evaluated and classified as metaphase I and metaphase II. The success of oocyte cryopreservation in each group was evaluated according to fertilization rate after the insemination procedure. Metaphase II oocytes had a fertilization rate of 33% (frozen) and 84% (fresh), whereas metaphase I oocytes had a 24% (frozen) and a 79% (fresh) fertilization rate. Metaphase I oocytes can mature to the metaphase II stage after having been frozen, metaphase II oocytes may be more vulnerable to chromosome damage, and the nuclear stage prior to freezing has no significant effect on the fertilizability of the frozen-thawed oocytes.

Animals↗

Induction of multiple follicular development as a therapy for unexplained or male-related infertility.

Most invasive techniques (i.e., in-vitro fertilization, gamete intrafallopian transfer) used for the therapy of unexplained or male-related infertility involve the induction of multiple follicular development (MFD). The efficacy of MFD in conjunction with a non-invasive technique (artificial insemination with husband's semen) was evaluated in a group of 41 couples with long-lasting infertility. MFD was obtained by means of clomiphene citrate and exogenous gonadotropins. Within 6 months of treatment, pregnancy was achieved by 52.2% of couples with male-related infertility and by 54.5% of couples with unexplained infertility. Sperm parameters, age of the female partner and preovulatory estradiol peak did not show any significant difference between couples who conceived and those who did not. It is concluded that induction of MFD represents an effective therapy and might replace invasive techniques for the treatment of the above conditions.

Adult↗

Assisted reproduction: a reassuring picture.

Many couples seek solutions to problems of infertility by using assisted reproduction techniques. Despite very different beginnings, children conceived after donor insemination, ovum donation, in-vitro fertilisation or gamete intrafallopian transfer show no adverse long term effects, either physically or psychosocially.

Fertilization in Vitro↗

Obstetric and gynecologic devices; reclassification and classification of medical devices used for in vitro fertilization and related assisted reproduction procedures--FDA. Final rule.

The Food and Drug Administration (FDA) is announcing that it is reclassifying instrumentation intended for use in in vitro fertilization (IVF) and related assisted reproduction technology (ART) procedures, including but not limited to gamete intrafallopian transfer (GIFT), embryo transfer (ET), and intracytoplasmic sperm injection (ICSI), from class III (premarket approval) to class II (special controls). FDA is also reclassifying assisted reproduction microscopes and microscope accessories from class III to class I. This reclassification is on the Secretary of the Department of Health and Human Services' (the Secretary's) own initiative based on new information. Accordingly, the order is being codified in the Code of Federal Regulations. Upon the effective date, this Federal Register document may be cited in the absence of an existing predicate device which would be used to support substantial equivalence. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a draft guidance entitled "Devices Used for In Vitro Fertilization and Related Assisted Reproduction Procedures: Submission Guidance for a 510(k)."

Device Approval↗

Hysteroscopic insemination of small numbers of spermatozoa at the uterotubal junction of preovulatory mares.

Mares were inseminated with motile spermatozoa suspended in 30-150 microliters Tyrode's medium directly onto the uterotubal papilla at the anterior tip of the uterine horn, ipsilateral to the ovary containing a dominant preovulatory follicle of > or = 35 mm in diameter, by means of a fine gamete intrafallopian transfer (GIFT) catheter passed through the working channel of a strobed light videoendoscope. Insemination of 10, 8, 25, 14, 11 and 10 mares with, respectively, 10.0, 5.0, 1.0, 0.5, 0.1 or 0.001 x 10(6) motile spermatozoa resulted in conception rates of, respectively, 60, 75, 64, 29, 22 and 10%. Deposition of 1.0 x 10(6) motile spermatozoa onto the uterotubal papilla began to approach the limit of successful fertilization. These doses are far lower than the 3-15 x 10(9) spermatozoa normally ejaculated by fertile stallions during mating, and the accepted minimum dose of 500 x 10(6) spermatozoa used for conventional uterine body insemination in mares. The simplicity of the technique offers a practical means of exploiting new breeding technologies that require very small numbers of spermatozoa in horse breeding.

Animals↗

Multifetal reduction of triplets and pregnancy outcome.

Multifetal pregnancy reduction has been suggested as a strategy to improve pregnancy outcome in grand multiple gestations of three or more fetuses. We prospectively investigated multifetal pregnancy reduction in 13 women with triplet pregnancies in the first trimester following ovulation induction, in vitro fertilization, or gamete intrafallopian transfer procedures. Eleven women whose triplet pregnancies followed similar reproductive technologies and who declined or were not offered the procedure were managed expectantly. Mean (+/- standard deviation) infant birth weight was 2227 +/- 478 g in the multifetal reduction group and 2239 +/- 399 g in the group managed expectantly. Gestational age was 35.5 +/- 2.3 weeks in the study group and 35.7 +/- 2.5 weeks in the triplets managed expectantly. Newborn hospital days as well as newborn and maternal complications were not statistically different between the management groups. Maternal interventions included tocolytic medication, home uterine activity monitoring, and extended hospitalization, and were more common in the triplets managed expectantly than in the study group of triplets reduced to twins. Multifetal pregnancy reduction for triplet pregnancies does not necessarily improve pregnancy outcome, though it may be offered on the basis of parental choice.

Abortion, Induced↗

Adjunctive leuprolide therapy does not improve cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination of subfertile women.

Problems arising from controlled ovarian hyperstimulation for intrauterine insemination, such as premature luteinization and asynchronous ovarian follicular development, are identical to those encountered with controlled ovarian hyperstimulation for in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). It has been suggested that the adjunctive use of GnRH agonists for controlled ovarian hyperstimulation improves the efficiency of GIFT and IVF cycles. We hypothesized that adjunctive use of leuprolide acetate, a GnRH agonist, would have a similarly beneficial effect on cycle quality and cycle fecundity in subfertile women treated with controlled ovarian hyperstimulation and intrauterine insemination. We randomly assigned the first cycle of controlled ovarian hyperstimulation and intrauterine insemination for each of 97 subfertile women to include either human menopausal gonadotropins (hMGs) alone or hMGs following midluteal pre-treatment with leuprolide. If a pregnancy did not occur in the first cycle, the woman was given the other treatment in the second cycle. Although the cycles that included leuprolide required a larger amount of hMGs and more days of stimulation per cycle, the mean estradiol concentrations and numbers of follicles were not different. Despite prevention of premature luteinization with leuprolide, the cycle fecundity was not different between groups (0.11 with adjunctive leuprolide treatment and 0.22 with hMGs alone). We conclude that in unselected subfertile patients, the adjunctive use of leuprolide for controlled ovarian hyperstimulation and intrauterine insemination does not improve cycle fecundity compared with treatment cycles that do not include adjunctive leuprolide therapy.

Adult↗

Unexplained infertility.

Unexplained infertility is a multifactorial disorder of reproduction. This review examines the potential contribution of decreased uterine perfusion, obscure luteal phase defect, intrinsic endometrial factor ovum captor inhibitor, microscopic endometriosis, and psychologic factors for the cause of unexplained infertility. Although specific therapy for unexplained infertility does not exist and treatment-independent pregnancy frequently occurs in this group of patients, many couples pursue treatment. In vitro fertilization, gamete intrafallopian transfer, zygote intrafallopian transfer, superovulation with intrauterine insemination, and direct intraperitoneal inseminations are several treatment options reported to be successful. However, a randomized prospective study using a uniform diagnostic assessment, strict entry criteria, identical ovulation-induction schemes, and semen-processing protocols is lacking to determine which patients will be most appropriately treated with each procedure and which is more effective. Unexplained infertility is not and should not be considered a permanent state. These couples should be considered to be subfertile rather than infertile.

Female↗

The application of pentoxifylline in the stimulation of sperm motion in men undergoing electroejaculation.

The ability of pentoxifylline to stimulate the motion characteristics of antegrade and retrograde sperm collected at the time of electroejaculation with a rectal probe was assessed in six neurologically impaired men. Before electroejaculation, the bladder was rinsed and instilled with 20 to 30 ml Ham's F-10 medium. Washed sperm were incubated with various doses (0, 0.1, 1, and 3 mmol/L) of pentoxifylline. Video sequences were recorded at intervals from 0 to 4.5 hours and analyzed for sperm motion parameters using manual and computer-assisted semen analysis. The results were compared with equimolar concentrations of caffeine. Both pentoxifylline and caffeine demonstrated a dose-dependent stimulation of percent motility and other motion parameters. A maximal stimulation of two-fold to three-fold for both percent motility and curvilinear velocity, and 30% to 60% for straight line velocity was observed after incubation under these conditions. A significant increase in mean linearity was observed in samples incubated with 0.1 mmol/L pentoxifylline at 1.5 hours. Significant lateral head displacement was not observed at any time point. Two couples underwent gamete intrafallopian transfer (GIFT) in conjunction with this electroejaculation sperm stimulation procedure, and one has since delivered a normal child. These studies show that pentoxifylline stimulation can improve the movement characteristics of asthenospermic sperm from neurologically impaired men. Such sperm stimulation techniques do not affect the fertilization process and may improve the chances for conception in some cases of male-factor infertility.

Ejaculation↗

Parthenogenetic activation and development of fresh and aged human oocytes.

OBJECTIVE: To develop a systematic study of the parthenogenetic activation and early development of human oocytes. DESIGN: Human oocytes (both freshly retrieved and remaining unfertilized after exposure to spermatozoa) were exposed to alcohol or calcium ionophore and examined for evidence of activation. SETTING: Academic research department of a teaching hospital. PATIENTS, PARTICIPANTS: Couples donating oocytes were undergoing therapy for infertility with in vitro fertilization or gamete intrafallopian transfer. INTERVENTIONS: Gonadotropin-releasing hormone agonist and human menopausal gonadotropin were administered at therapeutic doses. MAIN OUTCOME MEASURES: After application of activation stimuli at varying doses and durations, oocytes were examined for evidence of meiotic reactivation, pronuclear formation, deoxyribonucleic acid content, and cleavage. RESULTS: Fresh and aged human oocytes can be activated parthenogenetically using a calcium ionophore but at lower rates than seen for mouse oocytes (typically 50% to 60% versus 90% to 100%, respectively). Ethanol was a poor activating agent (maximum activation rate 16%). Human parthenotes can complete division to the eight cell stage. CONCLUSIONS: These results indicate that parthenote embryos may provide a source of material to study changes that occur during early human development. The data also raise the possibility that some early human pregnancy losses may involve oocytes that have been parthenogenetically activated spontaneously.

Calcimycin↗

Intraperitoneal insemination in the treatment of male and unexplained infertility.

For couples with unexplained or male infertility, intraperitoneal (IP) insemination in induced cycles is a method that increases the chance of fertilization. Seventy-seven couples with male subfertility were subjected to 120 IP insemination cycles and 31 with unexplained sterility to 44 cycles. As a consequence of the treatment, 23 pregnancies were obtained, with pregnancy rates of 23% per cycle and 32% per patient for unexplained infertility and 11% and 17% for male subfertility. Pregnancy loss rate was quite elevated: 9 clinical abortions and 1 ectopic. Intraperitoneal insemination appears to be a relatively noninvasive way to deal with unexplained or male factor infertility, well worth trying before moving on to more invasive and costly approaches, such as gamete intrafallopian transfer or in vitro fertilization.

Abortion, Spontaneous↗