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Analytic variability and clinical significance of different assays for serum estradiol.

Recent reports in the clinical laboratory literature have raised questions about the accuracy of different methods of measuring serum estradiol. To determine whether between-method variability was clinically significant, we used five different commercial radioimmunoassay methods to measure the concentration of estradiol in sera from nine patients undergoing induction of ovulation for gamete intrafallopian transfer. There were large differences between the estradiol concentrations measured in the same samples by the different methods. Furthermore, apparent changes in concentration that would be regarded as clinically significant may reflect nothing more than the imprecision of the assay. Physicians using serum estradiol measurements to support therapeutic decisions should be aware that an excessive reliance on those measurements may be misleading.

Adult↗

Second-look laparoscopy after ectopic pregnancy.

During the 4-year period of 1984 to 1987, 102 women with ectopic pregnancy (EP) underwent second-look laparoscopy 6 to 10 weeks after EP surgery. Benefits of this procedure, e.g., adhesiolysis and/or selection of women for further fertility interventions (in vitro fertilization [IVF], gamete intrafallopian transfer [GIFT], tubal microsurgery), were evaluated. On the basis of the second-look laparoscopy, 13% of the women were offered tubal microsurgery and 14% recommended for IVF. Patients without risk factors for EP developed adhesions as frequently as those with known risk factors and no specific surgical procedure was correlated to impairment of the pelvic status. Almost 40% of the patients presented with an impairment of adhesions on the affected side compared with the status at the time of EP surgery. Lysis of adhesions was performed during the second-look laparoscopy in 42 patients (41%). We conclude that second-look laparoscopy should be recommended to all EP patients with a desire for pregnancy.

Female↗

Reproductive hormonal levels in Malay women with superovulatory cycles.

This paper presents a study of cycles with spontaneous luteinizing hormone (LH) surge in superovulatory Malay women during in vitro fertilization and gamete intrafallopian transfer programmes. Sixteen Malay women underwent ovarian stimulation for ovum pick up at the National Population and Family Development Board, Malaysia. Two cycles showed spontaneous LH surge, and comparisons were made between these two cycles and the cycles without surge. Further observations were made in their characteristics and differences in these two cycles as well as the relationship between progesterone and LH at the time and before the surge.

Adult↗

[Cervix factors as a cause of infertility].

The uterine cervix plays an important role in the natural fertilization process and, consequently, it is also a significant factor in infertility. In about 6% of infertile couples, the infertility is caused by the cervical factor. The post coital test (PCT) is the most essential diagnostic procedure. A good PCT result excludes the cervical factor as the cause of infertility. A poor or negative PCT result, on the other hand, only indicates that the cervical tract is the cause in the case of women with verified ovulation and in whom other causes have been excluded. Treatment of the cervical factor has always been difficult. Intrauterine insemination is the best documented treatment method with a pregnancy rate of about 30%. In future, gamete intrafallopian transfer (GIFT) and in vitro fertilization (IVF) may be alternatives in the treatment of infertility owing to the cervical factor.

Cervix Mucus↗

Pooled sequential ejaculates: a way to increase the total number of motile sperm from oligozoospermic men.

We investigated the yield of total number of motile spermatozoa from oligozoospermic men by pooling two closely spaced sequential ejaculates. Semen characteristics were compared between sequential ejaculates (within a period of 1 to 4 hours) of 18 oligozoospermic males (sperm concentration less than 20 X 10(6)/mL and total sperm count less than 40 X 10(6) in the ejaculate) and a control group of 16 normozoospermic men. Whereas the median total number of motile sperm of normozoospermic males significantly decreased from 70 X 10(6) in the first ejaculate to 23 X 10(6) in the second sequential ejaculate, such a decrease was not detected in oligozoospermic males, 3.6 X 10(6) and 3.1 X 10(6), respectively. The percent of normozoospermic and oligozoospermic men who demonstrated a decreased (less than 50%), a comparable (50% to 150%), or an increased (greater than 150%) total motile sperm count in the second ejaculate in comparison with the first ejaculate were 69%, 31%, and 0 versus 39%, 28%, and 33%, respectively. Consequently, pooling of two sequential ejaculates significantly increased the median total number of motile sperm from normozoospermic males by 144% and from oligozoospermic males by 329%, (to 10.2 X 10(6]. We suggest that pooling of two sequential ejaculates from oligozoospermic males is a simple and cost effective method to increase significantly the total number of motile sperm for intrauterine insemination, in vitro fertilization, gamete intrafallopian transfer, or semen cryopreservation.

Body Fluids↗

Performance and sensitivity of modern home pregnancy tests.

We have studied the performance of three currently available home pregnancy tests. The Advance is a test based on monoclonal antibodies in an enzyme immunoassay format that specifically detects hCG in urine. The positive results are determined by the presence of a blue color in a color stick (30 minutes). The Daisy 2 and FACT are tests based on monoclonal antibodies that specifically detect hCG in urine in a hemagglutination inhibition assay; positive results are demonstrated by the deposition of a dot ring at the bottom of the test tube (45 minutes). Thirty-five patients who eventually became pregnant in that cycle collected the first morning urine specimens from day of ovulation (determined by ultrasound) in artificial insemination donor (AID) cycles, or from the date of gamete intrafallopian transfer (GIFT) for 16 consecutive days. In each specimen, the Advance, Daisy 2, and FACT tests were performed; in addition, beta-hCG levels were determined by radioimmunoassay. All the home pregnancy tests studied can detect pregnancy as early as 9 or 10 days post-conception, and they give positive results at the time of the expected onset of menses in 70%, 95%, and 88% of cases for Daisy 2, Advance, and FACT, respectively. The sensitivity of the these home pregnancy tests was determined to be about 200 mIU/mL of urine after correlating their positive or negative results with the concentrations of urinary beta-hCG determined by radioimmunoassay.

Antibodies, Monoclonal↗

[The empty follicle syndrome: a biologic reality].

Two patients were admitted to our Gamete Intrafallopian Transfer (GIF) program, and received and ovulation stimulation protocol with Clomiphene Citrate and human menopausal gonadotropin (hMG). Human chorionic gonadotropin (hCG, 10,000 IU IM) was administered when follicle size achieved 18 mm adn oocyte retrieval was scheduled after 36 hours. The estradiol levels in both patients were 1,127 pg/ml respectively at the time hCG was administered, which demonstrates an excellent response to the stimulation. Follicle aspiration was accomplished by transvaginal ultrasound-guided puncture or laparoscopy, and we were unable to recover oocytes in 17 follicles. Our findings support the existence of the "Empty Follicle Syndrome". This pathology may explain some of the infertility causes of our sterile population.

Adult↗

Role of gonadotropin releasing hormone agonists in ovulation induction.

The use of exogenous gonadotropins for ovulation induction in anovulatory women or for superovulation in gamete intrafallopian transfer or in vitro fertilization is complicated by premature luteinization, multiple gestation and ovarian hyperstimulation. Desensitization of the pituitary gonadotrophs can be achieved with gonadotropin releasing hormone (GnRH) agonists. The adjunctive use of GnRH agonists with exogenous gonadotropins prevents premature luteinization, possibly resulting in an improvement in ovarian stimulation.

Female↗

Monitoring gonadotropin therapy.

In the private clinical setting the use of Pergonal or Metrodin is a safe and efficient method of inducing ovulation; however, the known risks of those agents must be kept in mind at all times. By adhering to the guidelines listed here and administering Pergonal and then human chorionic gonadotropin in the prescribed manner, an ovulation rate of greater than 90% should be achieved. A six-month course of therapy with Pergonal should yield a pregnancy rate of 60-70%, provided that the fallopian tubes are normal, the sperm count is adequate and cervical mucus function is intact. Patients who do not become pregnant in six to nine months should be referred to tertiary centers for other procedures, such as in vitro fertilization and/or gamete intrafallopian transfer.

Chorionic Gonadotropin↗

Psychologic aspects of providing infertility services.

Psychologic issues enter into all aspects of providing infertility services. At the onset the infertile are faced with decisions regarding treatment options. Treatment involves uncertainty and lack of control and exposes the couple to the possibility of failure. The introduction of in vitro fertilization and gamete intrafallopian transfer exposes a proportion of couples to successive experiences of failure. These treatments have implications for emotional processing; some factors can increase the likelihood of impaired coping. Specific ways of dealing with the psychologic needs of infertile couples at all stages of their treatment can be helpful.

Adaptation, Psychological↗

[The LUF syndrome. A possible cause of unexplained infertility].

It is probable that one or several conditions may exist in which the oocyte is not released at the expected time of ovulation but where the follicle luteinizes around it. This cannot be demonstrated with the usual criteria for ovulation. A diphasic temperature curve, normal increase in progesterone and secretory development in the endometrium are observed. The reason for this phenomenon is not known but it may be induced experimentally by intake of prostaglandin-synthesis-inhibitors. It is difficult to determine with certainty in the individual case whether the egg has been released. The presence of an ovulation opening, a stigma which may be seen on the follicle by laparoscopy, marked increase in the concentration of progesterone and 17-beta-oestradiol in the peritoneal fluid and ultrasound demonstration of a collapsed follicle are good indicies. Defective release of the egg cell probably occurs periodically in cycli in normal fertile women but the condition appears to be more frequent in infertile women with endometriosis, with changes after pelvic inflammation and with "unexplained" infertility. As definite criteria for the condition are not available, no convincing investigations of the frequency are available and no controlled investigations of therapeutic method exist. Gametic intrafallopian transfer and in vitro fertilization and embryo transfer have been proposed as therapeutic measures.

Female↗

Early experience with the GIFT procedure.

Gamete intrafallopian transfer (GIFT) was performed in 19 cycles on 15 couples whose infertility had proven resistant to other treatments. Indications included infertility associated with immunologic factors, seminal deficiencies, endometriosis and infertility without a diagnosed etiology. Any history or finding of tubal disease served as an exclusion. Infertility was primary in ten couples and secondary in five, three of whom had conceived previously with a semen donor. Stimulation protocols included clomiphene citrate (CC) and human menopausal gonadotropins, CC alone and gonadotropins alone. Males were screened with the hamster egg sperm penetration assay. Four conceptions were recorded, and three are ongoing. Advantages of this procedure include acceptance by the major orthodox religions, avoidance of extracorporeal incubation and physiologic entry of the embryo into the uterine cavity. Disadvantages include the inability to determine if fertilization has occurred in the absence of pregnancy, the theoretical risk of increased ectopic gestation and tubal infection, and perhaps an increase in multiple gestations.

Adult↗

Future growth and development of hysteroscopy.

In less than two decades, hysteroscopy has evolved into a practical technique for the evaluation of the uterine cavity, with well-established indications such as evaluation of abnormal uterine bleeding and abnormal hysterograms as well as the treatment of intrauterine adhesions or the septate uterus, the removal of misplaced or embedded intrauterine devices, and the removal of submucous leiomyomas. As the use of hysteroscopy increases and more practitioners utilize it, new instrumentation and techniques are beginning to evolve, simplifying and facilitating not only a diagnostic examination, but also the more difficult and complex surgical interventions. Flexible endoscopes are being tested for possible use in the uterine cavity, and operative hysteroscopes with practical inflow and outflow accessory channels have been introduced. The accessory operative instrumentation has also been expanded and refined, and portable units for office examinations have been developed. The trend in the development of instrumentation is toward simplicity, effectiveness, and refinement in lenses with wider fields of view and accessory channels without compromising the total outer diameter of the endoscopes. As clinical applications expand as a result of increased use and proficiency in hysteroscopy, new applications undoubtedly will follow, such as closer study of the endometrium with and without additional magnification. This latter may permit a better understanding of the receptivity of the endometrium to the embryo, which may help in predicting successful nidations. Portable laser units with the capability to use the CO2 fiber undoubtedly will increase laser use through hysteroscopy, and in the near future, photodynamic therapy may become the best approach to the selective treatment of intrauterine lesions. The uterotubal junction will remain an attractive area for endoscopists to approach the fallopian tubes transcervically and eventually to accomplish tubal closure safely and effectively with the possibility of future reversibility. The hysteroscope will play an important role in new reproductive technologies, particularly those related to the gamete intrafallopian transfer via the uterine side and perhaps also for direct embryo transfers under visual control. The future of hysteroscopy thus is promising. The present diagnostic and therapeutic applications will not only become a standard of treatment but will expand as gynecologists will gain proficiency and confidence in this endoscopic method.

Endoscopes↗

[Sperm-immobilizing antibodies in serum, follicular fluid and ascites].

Antisperm antibodies appear to impair reproduction. Follicular fluids, ascites and sera taken at the time of oocyte recovery from patients undergoing gamete intrafallopian transfer (GIFT) were examined for the presence of sperm immobilizing antibodies and their immunoglobulin classes were determined. Three out of ten patients were found to have sperm immobilizing antibodies in their sera. The immunoglobulin classes of the antibodies were IgG and/or IgM, and no IgA class antibodies were detected. The same classes of antibodies found in sera also existed in follicular fluids and ascites in these patients. Furthermore, titers of the antibodies in follicular fluids and ascites were consistent with those of patients' sera.

Adult↗

Assisted reproduction techniques.

Many couples with infertility will require a form of assisted reproduction to achieve a pregnancy. Assisted reproduction techniques, including intrauterine insemination, gamete intrafallopian transfer and in-vitro fertilisation, are considered in this review.

Female↗

Micromanipulation at an infertility centre.

AIM: Human in vitro fertilisation (IVF) and gamete intrafallopian transfer have been used in the management of various forms of infertility. In cases of severe male-factor infertility, fertilisation can be a factor. In this study micromanipulation was used to increase fertilisation in such cases. METHODS: Two micromanipulation techniques, subzonal sperm injection (SUZI) and partial zona dissection (PZD), were used to assist fertilisation in patients with abnormal semen parameters. Ten couples with severe oligo-, terato- and asthenozoospermia participated in the SUZI programme. Seventy-three oocytes were obtained from these 10 patients. PZD was used on day 1 oocytes in cases of male infertility as well as a rescue attempt on day 2 oocytes when fertilisation had failed after routine insemination. RESULTS: The SUZI technique had a fertilisation rate of 37.7%. In this group, a biochemical pregnancy was achieved. Differences between the fertilisation rate of conventional IVF (33.3%) and PZD (56.3%) in cases of male infertility, were not statistically significant although a clinical difference could be detected. PZD was statistically effective in facilitating fertilisation (37.5% v. 8.3%) in couples where this procedure was introduced to reinseminate 24-hour-old unfertilised oocytes. Four patients received PZD reinseminated embryos. An average of 1.45 PZD embryos were replaced and 1 implantation pregnancy was confirmed. CONCLUSION: The micromanipulation results are encouraging and seemed to increase the efficiency of IVF in humans. Furthermore, our data support the conclusion that micromanipulation procedures can bring about pregnancies.

Female↗

Effect of a gonadotropin-releasing hormone agonist on luteinizing hormone receptors and steroidogenesis in ovarian cells.

OBJECTIVE: To examine the effect of a gonadotropin-releasing hormone agonist (GnRH-a), leuprolide acetate (LA), on human chorionic gonadotropin/luteinizing hormone (LH) receptors content and progesterone (P) and estradiol (E2) production in cultured granulosa or luteal cells. DESIGN: Prospective. SETTING: Private Fertility Clinic and National Research Institute. PATIENTS: Twenty patients undergoing in vitro fertilization or gamete intrafallopian transfer programs. RESULTS: Human chorionic gonadotropin/LH receptors in human granulosa cells increased after 48 hours of culture, and LA inhibited such effect. Leuprolide acetate, 1 ng/mL, in the cultures produced an increase in P production. On the contrary, LA inhibited E2 production. Additionally, the in vivo effect of LA (2 micrograms/rat per 7 days) was studied in corpus luteum of superovulated rats. Luteal cells from LA-treated rats in culture produced lower P than the controls but showed an increase in aromatase activity. Luteal LH receptors declined after 48 hours of culture with LA. CONCLUSION: The high doses of gonadotropin necessary to induce ovarian hyperstimulation when GnRH-a is administered could be related with an inhibitory effect of these agonists on LH receptors and aromatase activity.

Animals↗

Unexplained infertility.

Unexplained infertility is a nebulous diagnosis that is justified only after a thorough and meticulous investigation of both partners. Even if the five basic tests constituting the infertility investigation have not revealed an abnormality, there may be a specific cause. Diagnosing unexplained infertility in this setting is somewhat arbitrary. In such couples, spontaneous pregnancies have been reported, with an average cumulative pregnancy rate of 60% after three years. Some additional testing, however, is appropriate. Treatment of unexplained infertility, however, tends to be empiric if no cause is found. Our current therapeutic plan entails superovulation with intrauterine insemination for at least four cycles. A cycle fecundity in the range of 0.23 may be expected but is highly influenced by the woman's age, with cycle fecundity dropping to as low as 0.05 after age 40. Alternatives to superovulation and intrauterine insemination are direct intraperitoneal injection of sperm with or without oocytes and intrafollicular injection of sperm. Gamete intrafallopian transfer and in vitro fertilization (IVF) are appropriate after a trial of empiric therapy. Our preference is to carry out IVF because the knowledge that fertilization has occurred is important in that fertilization failure is a known cause of unexplained infertility.

Diagnosis, Differential↗