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Distinction between early and late ovarian hyperstimulation syndrome.

OBJECTIVE: To compare patient and cycle characteristics among three study groups: early ovarian hyperstimulation syndrome (OHSS), late OHSS, and non-OHSS. DESIGN: Prospective observational study. SETTING: University assisted conception service. PATIENT(S): Women undergoing in vitro fertilization, intracytoplasmic sperm injection or gamete intrafallopian transfer treatment at Bristol University In Vitro Fertilization Service between January 1, 1995, and December 31, 1998. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Patient age, prevalence of polycystic ovaries, gonadotropin requirement, peak serum estradiol (E(2)) concentration, number of oocytes retrieved, clinical pregnancy rate, number of gestation sacs, and severity of OHSS. RESULT(S): Women with early OHSS had significantly higher serum E(2) levels and lower gonadotropin requirements than did the other groups. Cycles with either early or late OHSS had significantly more oocytes collected than those without OHSS. Serum E(2) and oocyte numbers did not accurately predict the risk of developing late OHSS. Clinical pregnancies occurred in all cycles with late OHSS, and multiple pregnancies were significantly more frequent in the late OHSS group than in the other groups. Late OHSS was more likely than early OHSS to be severe. CONCLUSION(S): Early OHSS relates to "excessive" preovulatory response to stimulation, whereas late OHSS depends on the occurrence of pregnancy, is likelier to be severe, and is only poorly related to preovulatory events.

Adult↗

Electroejaculation and assisted reproductive technologies in the treatment of anejaculatory infertility.

OBJECTIVE: To determine the efficacy of electroejaculation in combination with assisted reproductive technology (ART). DESIGN: Case series. SETTING: University fertility program. PATIENT(S): One hundred twenty-one consecutive couples seeking treatment of anejaculatory infertility. INTERVENTION(S): Electroejaculation with IUI, or gamete intrafallopian transfer or IVF. MAIN OUTCOME MEASURE(S): Pregnancy and pregnancy outcome. RESULT(S): Fifty-two couples became pregnant (43%), 39 by IUI alone (32.2%). Cycle fecundity for IUI was 8.7%. No difference in cycle fecundity was seen among ovarian stimulation protocols (clomiphene citrate, 7.6%, hMG, 13.2%, and natural cycle, 11.2%). Pregnancy was unlikely when the inseminated motile sperm count was <4 million. Female management protocol and etiology of anejaculation did not affect results. Patients undergoing IVF had higher cycle fecundity (37.2%) than did those undergoing IUI. The rates of spontaneous abortion and multiple gestations were 23% and 12%, respectively. CONCLUSION(S): Electroejaculation with stepwise application of ART is effective in treating anejaculatory infertility. Intrauterine insemination with the least expensive monitoring protocol should be used for most couples, because use of more expensive monitoring did not improve results. It is cost-effective to bypass IUI and proceed directly to IVF in men who require anesthesia for electroejaculation and in those with a total inseminated motile sperm count < 4 million.

Ejaculation↗

Assisted reproduction in patients with early-stage ovarian malignancies.

OBJECTIVE: To determine the outcome of women with early-stage ovarian malignancies who subsequently underwent assisted reproductive technologies (ART). DESIGN: Retrospective study. SETTING: Academic assisted reproductive technology program. PATIENT(S): Four infertile women who were previously diagnosed with early-stage ovarian malignancies. INTERVENTION(S): Controlled ovulation hyperstimulation, IVF, and/or gamete intrafallopian transfer treatments using clomiphene citrate and/or gonadotropins. MAIN OUTCOME MEASURE(S): Development of tumor recurrence and disease-free interval. RESULT(S): All four women remain free of disease for up to 15 years after treatment. Three of the four women achieved pregnancy. CONCLUSION(S): In patients with early-stage ovarian malignancies, conservative therapy followed by ovarian stimulation for assisted reproduction is an acceptable strategy.

Adult↗

The mind/body program for infertility: a new behavioral treatment approach for women with infertility.

There is increasing evidence that a behavioral treatment approach might be efficacious in the treatment of the emotional aspects of infertility and may lead to increased conception rates. The first 54 women to complete a behavioral treatment program based on the elicitation of the relaxation response showed statistically significant decreases in anxiety, depression, and fatigue as well as increases in vigor. In addition, 34% of these women became pregnant within 6 months of completing the program. These findings established a role for stress reduction in the long-term treatment of infertility. They further suggest that behavioral treatment should be considered for couples with infertility before or in conjunction with reproductive technologies such as intrauterine insemination and gamete intrafallopian transfer.

Cognition↗

Treatment of endometriosis with a delayed release preparation of the agonist D-Trp6-luteinizing hormone-releasing hormone: long-term follow-up in a series of 50 patients.

Fifty patients with proven endometriosis were treated for 6 to 9 months with a delayed release preparation of microcapsules of the luteinizing hormone-releasing hormone (LH-RH) agonist D-Trp6-LH-RH, injected intramuscularly at monthly intervals. After a transitory ovarian stimulation at the onset of treatment, serum estradiol was suppressed to menopausal levels (50 pg/mL). This state of hypogonadism was reversible after the discontinuation of treatment, and menses resumed within 4 months after the last injection. Pelvic pain was relieved during treatment in 87.5% of patients. After a follow-up period of up to 37 months, 24 patients are in clinical remission and 9 experienced recurrence of endometriosis 7 to 14 months after completing treatment. One patient failed to respond to therapy with the agonist and 7 patients were lost to follow-up. Among 16 previously infertile patients with no other factors contributing to infertility, 7 became pregnant; 2 of these pregnancies were the result of gamete intrafallopian transfers. An eighth patient without documented infertility also conceived spontaneously. Side effects due to hypoestrogenism were reported by nearly all patients. In conclusion, D-Trp6-LH-RH microcapsules are effective and easily-administered agents for the treatment of endometriosis.

Adult↗

Transient cooling to room temperature can cause irreversible disruption of the meiotic spindle in the human oocyte.

The effect on the microtubule system of human oocytes of cooling to room temperature for either 10 or 30 minutes has been investigated. Changes in spindle organization were found in all oocytes cooled for 30 minutes compared with control oocytes kept at 37 degrees C throughout. These changes included reduction in spindle size, disorganization of microtubules within the spindle itself, and sometimes a complete lack of microtubules. In some oocytes, chromosome dispersal from the metaphase plate was associated with these changes. Cooling the oocyte to room temperature for only 10 minutes produced a similar pattern of disruption to spindle structure in many cases. The spindles in oocytes that were cooled for either 10 or 30 minutes and then allowed to recover at 37 degrees C for either 1 or 4 hours were found to resemble those in noncooled control oocytes in less than one half of the cases examined, although in only a few cases did the chromosomes remain dispersed. The significance of these findings for the handling of oocytes during gamete intrafallopian transfer and in vitro fertilization procedures is discussed in relation to the levels of aneuploidy detected in early human embryos.

Chromosomes↗

Endometrial inadequacy after treatment with human menopausal gonadotropin/human chorionic gonadotropin.

The incidence of abnormal endometrial histology in patients undergoing human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG) treatment during cycles of in vitro fertilization (IVF) or gamete intrafallopian transfer has been reported to be 52% to 91%. The incidence of endometrial inadequacy, as judged by a single late luteal endometrial biopsy, has not been studied in hMG/hCG non-IVF cycles. In the current study, 30 patients (30 cycles) undergoing hMG/hCG treatment were evaluated by an endometrial biopsy. The incidence of endometrial inadequacy was found to be 27%. No preovulatory predictors for endometrial inadequacy could be identified. Therefore, luteal support for patients undergoing non-IVF hMG/hCG cycles should be considered.

Adult↗

Programming in vitro fertilization for a 5- or 3-day week.

OBJECTIVE: To schedule oocyte retrievals on either 5 or 3 days per week in in vitro fertilization (IVF) cycles. DESIGN: Human chorionic gonadotropin (hCG) administration was delayed by at least 24 hours in patients undergoing superovulation to avoid egg collections on weekends (group 1). Encouraged by the results, a further prospective study in which oocyte retrievals were programmed for only 3 days a week was undertaken (group 2). SETTING: Hammersmith Hospital, a tertiary referral unit. PATIENTS: All patients undergoing IVF treatment were included. MAIN OUTCOME MEASURES: To schedule oocyte retrievals on either 5 or 3 days per week. RESULTS: Only 4.0% of egg collections (12/303) occurred on weekends compared with 12.6% (22/175) before delaying hCG. In group 2 (n = 215), only four egg collections (2.1%) had to be performed out of schedule. Delaying administration of hCG had no detrimental effects. CONCLUSIONS: Delayed administration of hCG allows scheduling oocyte retrievals on either 5 or 3 days per week, leading to a substantial decrease in out-of-hours oocyte retrievals, reducing cycle costs, and facilitating efficiency. The method is applicable to assisted reproduction specialized units as well as district general hospitals that use gonadotropin-releasing hormone analogs in their superovulation regimens before IVF, gamete intrafallopian transfer, or intrauterine insemination.

Chorionic Gonadotropin↗

Transcervical selective salpingography: a diagnostic and therapeutic approach to cases of proximal tubal injection failure.

OBJECTIVE: Evaluation of selective salpingography for diagnosis and treatment of tubal injection failure during hysterosalpingography (HSG). DESIGN: Prospective study. SETTING: Obstetrics and Gynecology Department, University of Genoa (Italy)--tertiary care. PATIENTS: One hundred eighty infertile women with unilateral or bilateral proximal tubal injection failure during HSG were submitted to the procedure. INTERVENTION: Under fluoroscopy, a 4.5-F nylon catheter (3-F tip) was inserted into the ostium with or without the aid of a J-shaped, coaxial, angiographic guide wire, and 2 to 3 mL of contrast medium were injected. The procedure lasts 20 to 30 sec/tube. MAIN OUTCOME MEASURES: Of 155 tubal ostia, 145 (94.2%) were catheterized. RESULTS: Of the 146 catheterized tubes, 110 (75%) were rendered patent. Of the others, 21 (14.3%) presented hydrosalpinx or distal obstructions, and isthmic obstruction was present in 5 (3.4%). Patency of at least one tube was achieved in 82 (81.2%) of the 101 catheterized women; 8 conceived spontaneously and 11 after gamete intrafallopian transfer to the recanalized tube. CONCLUSIONS: During HSG, selective salpinography can be performed when proximal injection failure is observed to determine its cause or to restore patency.

Adult↗

Failure of intrauterine insemination in a refractory infertility population.

Intrauterine insemination by itself for multiple and/or severe infertility factors had no benefit over cervical cap with whole ejaculate or coitus in this study. The PRs for IUI and cervical cap with whole ejaculate or coitus were similar and low, suggesting that IUI by itself has limited, if any, utility in enhancing PRs in this type of infertility population. Couples attempting IUI should be advised about the low probability of achieving pregnancy. Ovulation stimulation and/or heterologous donor insemination, IVF, or gamete intrafallopian transfer may be beneficial therapeutic options.

Adult↗

Inhibin and relaxin concentrations in early singleton, multiple, and failing pregnancy: relationship to gonadotropin and steroid profiles.

OBJECTIVE: To examine the inter-relationships between inhibin, relaxin, steroid concentrations, estradiol (E2), progesterone (P), and gonadotropins in early pregnancy. DESIGN: Hormone concentrations in plasma were measured during the luteal phase of subjects who became pregnant (n = 58) or failed to become pregnant (n = 47) after ovarian hyperstimulation for in vitro fertilization-gamete intrafallopian transfer (IVF-GIFT) (group 1). A further group of subjects became pregnant (n = 7) or failed to become pregnant (n = 8) during endocrinology tracking of a natural cycle (group 2). Blood was obtained every 3 days in the luteal phase from day 5 in group I (day 0 was oocyte recovery) and from day 0 (first increase in luteinizing hormone [LH]) in group II. RESULTS: Progesterone and E2 were increased over nonpregnant values by day 11 (P) and day 16 (E2) in group I and by day 11 (E2 and P) in group II. Inhibin and relaxin concentrations were significantly increased by day 16 in group I (often by day 11) and by day 14 in group II pregnancy subjects. A direct relationship existed between inhibin, P, relaxin, and human chorionic gonadotropin (hCG). Subjects who had twin pregnancies demonstrated higher concentrations of all hormones and often exhibited increases earlier (by day 11 in group I) than singleton pregnancy subjects. Pregnancies that ended in miscarriages tended to have lower concentrations of P and inhibin. None of the hormones reliably discriminated between the clinical conditions of blighted ovum and of spontaneous abortion, and the predictive value of any hormone measured for miscarriage was not high. CONCLUSIONS: The trend of inhibin and relaxin concentrations closely parallels rises in P during early pregnancy. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are suppressed very early in pregnancy. The suppression of LH and FSH in hyperstimulated cycles is more governed by E2 than inhibin in stimulated cycles. Some subjects destined to miscarry exhibit abnormal endocrine changes very early in the luteal phase.

Abortion, Spontaneous↗

A new computerized method of reading sperm morphology (strict criteria) is as efficient as technician reading.

OBJECTIVES: To compare the ability of a computerized method of sperm morphology with the manually recorded method in predicting in vitro fertilization (IVF) results, to compare results obtained by both methods, and to determine the intraobservation variability. DESIGN, SETTING, PATIENTS: Forty-three stained semen slide preparations from two large level-three academic institutions' reproductive endocrinology units (IVF programs) were blindly evaluated, and the sperm were classified into normal and amorphous forms. RESULTS: Experiment 1: Twenty-one slide preparations from the Tygerberg gamete intrafallopian transfer program were manually evaluated; the fertilization rates for the groups with < 14% and > 14% normal sperm forms were 33.3% (15/45 oocytes) and 76.6% (46/60 oocytes), respectively. Corresponding fertilization rates with FERTECH were 46.8% (30/64) and 75.6% (31/41). Experiment 2: Twenty-two slide preparations from the Norfolk IVF program were evaluated. The manual method reported a fertilization rate in the group with < 14% normal forms of 27.4% (14/51 oocytes) compared with 90.0% (127/141 oocytes) in the group with > 14% normal forms. Corresponding figures for the FERTECH method were 33.9% (18/53) and 88.4% (123/139), respectively. Experiment 3: When the 43 slide preparations were blindly evaluated using both methods, 84% of the FERTECH evaluations correlated well with the manual method and FERTECH ability to diagnose the subfertile male (< 14% normal forms) was 95% (sensitivity). Experiment 4: A total of 16 different slides (8 per group) were randomly selected and analyzed five times (100 cells per reading) by the computerized method. The slides were obtained from men with normal sperm morphology of < 14% and > 14% as classified by the manual method. In the first group (< 14%) 97.5% (39/40) of the readings classified the sperm in the proper category, whereas in the second group (> 14%) 95% (38/40) of the cases were correctly identified. CONCLUSION: Using strict criteria for morphology evaluation, there is a positive and significant correlation between FERTECH evaluation and manual assessment. The reproducibility of the computerized method and the ability to distinguish between fertile and subfertile groups using those criteria are good.

Evaluation Studies as Topic↗

Pharmacologic induction of multiple follicular development improves the success rate of artificial insemination with husband's semen in couples with male-related or unexplained infertility.

The use of artificial insemination with husband's semen (AIH) as treatment for couples with male-related or unexplained infertility is often disappointing. The aim of the present study was to evaluate whether the induction of multiple ovulation can increase the pregnancy rates in couples treated with AIH. Multiple follicular development was induced by means of clomiphene citrate (CC) plus purified follicle-stimulating hormone (FSH) in 17 couples undergoing AIH for male-related or unexplained infertility. In spite of the long duration of infertility (greater than 6 years), 10 couples (58.8%) achieved pregnancy within 6 months of treatment. This figure was significantly higher than that obtained in 120 couples who underwent AIH either during spontaneous cycles or after induction of follicular development with CC alone. These results suggest that the availability of multiple mature oocytes increases the conception rate during each cycle, as reported for in vitro fertilization (IVF) programs. It is therefore suggested that a trial of induction of multiple follicular development be performed in couples with male-related or unexplained infertility before their inclusion in protocols for invasive procedures, such as IVF or gamete intrafallopian transfer.

Clomiphene↗

Ovum donation--a simplified approach.

To date, ovum donation (OD) has involved luteinizing hormone (LH) synchronization between recipient and donor for normally cycling women, and a complex steroid replacement regimen given on a sequential and incremental basis for women with primary or secondary ovarian failure. The authors designed a simple hormonal regimen applicable to both normally cycling women starting early in the cycle, and to those with ovarian failure. It consists of administering 2 mg estradiol (E2) valerate orally three or four times daily, augmented with either 100 mg progesterone (P) in ethyl oleate intramuscularly daily or 100 mg oral progesterone (P) orally three times daily, starting on the day preceding the recovery of the donated oocytes. Gamete intrafallopian transfer procedure was undertaken for women with patent tubes and in vitro fertilization for those with obstructed tubes. The authors report their preliminary experience with 17 women who underwent ovum donation.

Administration, Oral↗

Follicular stimulation for in vitro fertilization using pituitary suppression and human menopausal gonadotropins.

Multiple follicular stimulation is a prerequisite to the efficient use of in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT). For some individuals, however, this stimulation may be difficult using standard superovulation protocols because of dominant follicle formation, suboptimal estradiol response, or premature luteinizing hormone surge. A group of such individuals with several previous failed attempts at superovulation were studied. Follicular stimulation was accomplished using a long-acting agonist of gonadotropin-releasing hormone (GnRH) for pituitary suppression followed by human menopausal gonadotropin (hMG) for follicular stimulation. Fourteen cycles (12 IVF, 2 GIFT) were completed in 12 individuals. There were no cycle cancellations. Mean number of prior cycle cancellations per patient was 3.1 +/- 0.4. Mean number of mature oocytes recovered was 3.9 +/- 0.5. Two pregnancies resulted. Pituitary suppression with a long-acting agonist of GnRH followed by hMG appears to be an effective adjunct to current superovulation regimens.

Adult↗

Unexplained infertility--the value of Pergonal superovulation combined with intrauterine insemination.

Sixty-two women with unexplained infertility were studied. Fifteen (group 1) had timed intrauterine insemination (IUI), 25 (group 2) were treated by Pergonal (Serono Laboratories, Ltd., Welwyn Garden City, England) superovulation, and 22 (group 3) underwent Pergonal superovulation combined with IUI. Where Pergonal treatment was followed by insemination, a significantly greater pregnancy rate per cycle (P less than 0.05) was achieved, whether this group of patients was compared with those treated by IUI alone or with those treated with Pergonal alone. Moreover, the pregnancy rate in group 3 was comparable to that reported following gamete intrafallopian transfer (GIFT). The authors therefore suggest this form of treatment for patients with unexplained infertility prior to their referral to the more invasive procedure of GIFT.

Adult↗

Sperm antibodies and human in vitro fertilization.

In order to directly evaluate the effects of sperm antibodies in human in vitro fertilization (IVF), the authors preincubated donor sperm in female sera containing sperm antibodies and then inseminated supernumerary human oocytes from a gamete intrafallopian transfer (GIFT) program. The sperm were incubated for 30 minutes in medium containing 20% serum with antisperm activity (Test); or no antisperm activity (Control) as assessed by the immunobead test (IBT). Each oocyte was inseminated with 1 to 2 X 10(5)/ml of the preincubated motile sperm with Control or Test treatments allocated on a random basis. Six positive sera were tested in 17 experiments, resulting in a fertilization rate of 41% (25/61) versus 84% (36/43) for controls (P less than 0.001). When considered individually, three of six positive sera caused significant inhibition. The only serum that gave complete inhibition had the highest titer for IgG (10,000) and lower IgA (100). Absorption with protein A reduced the IgG titer to less than 10 and removed the fertilization inhibitory activity. These results confirm that sperm antibodies from female sera can inhibit human IVF.

Antibodies↗

Efficacy of human menopausal gonadotropins as therapy for abnormal cervical mucus.

Traditional therapies for abnormal cervical mucus, other than timed intrauterine insemination, are noteworthy for being ineffectual. Patients (n = 27) with documented abnormal Insler scores in repetitive cycles and failure to conceive with traditional treatments were screened with conjugated equine estrogens (CEE) for estrogen responsiveness of the cervix. Only 5 patients were found unresponsive. Seventeen patients with CEE-responsive cervices then were treated with human gonadotropins (hMG), initially 1 ampule days 5 to 11. If the mucus failed to improve, the hMG was increased to standard doses. Eight patients responded to 1 ampule hMG with improved mucus and conception. The remainder required 2 ampules hMG. In patient cycles with corrected cervical mucus, the viable fecundibility (fv) was 0.35. This is significantly higher than predicted for this population (fv = 0.09; P less than 0.01). In all, 14 of 17 patients conceived viable pregnancies during hMG treatment. It is concluded that graduated hMG is efficacious in treating patients with abnormal cervical mucus responsive to CEE. It is preferable to either in vitro fertilization or gamete intrafallopian transfer, based on both cost and efficacy for most patients.

Cervix Mucus↗