The new frontier of reproductive age.
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Biomedical subjects
Publications and source records attributed to M M Quigley.
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Forty-five women were evaluated as candidates to donate oocytes to an infertile couple. Twenty-four women completed a cycle as oocyte donors. Follow-up data on donor satisfaction were obtained for 23 women. Ninety-one per cent were moderately to extremely satisfied with the experience and 74% would donate for another cycle if given the chance. Transient adverse psychological symptoms were reported by two donors but were resolved with medical or psychological treatment. Two women became pregnant soon after donation, one unintentionally. Psychological risk factors predicted donor candidates' decisions to participate and their compliance but were not predictive (within the group that completed a cycle) of donor satisfaction as follow-up or recipient pregnancy.
IVF with donated oocytes, followed by embryo placement in the uterus of a recipient who has been primed with exogenous steroids, is a successful treatment for special cases of infertility. Preliminary results indicate that the success rate in this situation is even greater than that usually seen with normal IVF (with placement of the embryos back into the uteri of the women from whom the oocytes were recovered). Although different sources for donated oocytes have been identified, the use of "excess" oocytes from IVF cycles and the attempted collection of oocytes at the time of otherwise indicated pelvic surgery have ethical and practical problems associated with their use. We have herein described the establishment of a successful program relying on anonymous volunteers who go through ovarian stimulation, monitoring, and oocyte recovery procedures solely to donate oocytes. The potential donors go through an exhaustive screening and education process before they are accepted in the program. Psychological evaluation of our potential donors indicated a great degree of turmoil in their backgrounds and a wide variety of motivations for actually participating. Despite the extensive educational and screening process, a substantial percentage of the donors did not complete a donation cycle, having either voluntarily withdrawn or been dropped because of lack of compliance. Further investigation of the psychological aspects of participating in such a program is certainly warranted. The use of donated oocytes to alleviate specific types of infertility is quite successful, but the application of this treatment is likely to be limited by the relative unavailability of suitable oocyte donors.
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Failure of epididymal spermatozoa from T/t mutant mice, but not from t/t individuals, to fertilize oocytes in vitro was partially overcome by opening a small aperture in the zona pellucida with acidified Tyrode's solution to permit direct access of the spermatozoon to the vitellus. This study provides a model system to evaluate requirements for successful zona drilling in the treatment of human infertility and further insights into the effects of the t complex on sperm fertility.
A study of mouse gamete processing for in vitro fertilization (IVF) under various conditions showed that it is necessary to control the atmosphere if the temperature is raised from 22 degrees C to 37 degrees C. The data suggest that maximum IVF success is attained by processing the gametes at 37 degrees C, under an atmosphere of 5% O2 and 5% CO2, and overlaying the medium with silicone oil.
To investigate whether the provision of increased gonadotropins would enhance follicular recruitment and selection, women not responding (N = 18) to our standard clomiphene citrate (CC)-human menopausal gonadotropin (hMG) regimen were treated with increased hMG (treatment cycle II). Estradiol levels were higher in treatment cycle II and these differences were significant on days 8 and 9 (P less than or equal to 0.05 and P less than or equal to 0.03, respectively). On day 9, better follicular development was seen in cycle II (P less than or equal to 0.05). While none of the patients responded in cycle I, 10 of 18 responded in cycle II. Of the 10 responders, 2 conceived following in vitro fertilization and embryo placement. Increasing the dose of hMG improved the development of a cohort of follicles so that aspiration and possible pregnancy were achieved in women who were previously unresponsive to therapy.
Recognizing the association between plasma progesterone (P) and an imminent LH surge, we investigated the frequency of P elevation in our stimulation protocol (clomiphene citrate-human menopausal gonadotropins). P was measured retrospectively on the day before, the day of, and the day after human chorionic gonadotropin hCG administration. The means +/- 2 standard deviations for P were as follows: day before hCG, 0.58 +/- 0.86; day of hCG, 0.64 +/- 0.56; and day after hCG, 1.47 +/- 1.22. Seven patients (8%) had P levels greater than 2 SD above the mean. Significant P elevations prior to hCG are infrequent with this protocol, and in the few patients with raised P a trend toward lowered fertilization was noted. The low incidence of P elevation may be secondary to the administration of hCG in a timely manner on the sixth day of estradiol (E2) rise.
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The degree and normality of nuclear maturation were assessed with the fluorochrome Hoechst 33342 in two groups of inseminated human oocytes that had failed to undergo fertilization. Group 1 consisted of 67 oocytes from 27 patients, each of whom had at least two other oocytes that had been fertilized and had cleaved. Group 2 consisted of 65 oocytes from 14 patients, none of whose oocytes had been fertilized. In group 1, 52.3% of the oocytes were found to be immature (germinal vesicle stage or metaphase-telophase I), whereas in group 2 only 26% were found to be immature. Thus oocyte nuclear immaturity was the major cause of fertilization failure when companion oocytes were fertilized. When no oocytes of a patient were fertilized, most oocytes were found to be mature, so other factors, such as sperm dysfunction or zona binding abnormalities, must account for most of the fertilization failure in this group of patients.
The authors' program for matched, anonymous oocyte donation has resulted in two successful pregnancies among the first eight oocyte recipients. All oocyte recipients to date have had ovarian failure or absence with premature ovarian failure the most common cause. All recipients were cycled on a program of incremental oral micronized estradiol and intramuscular progesterone-in-oil. Thirteen candidates for oocyte donation were screened to obtain 8 donors. One donor candidate was excluded because of her medical history. The psychological screening of 2 of the other donor candidates (who subsequently did not complete the donation cycle) revealed a primary motive of financial gain. In general, the psychological profiles of donor candidates revealed a high incidence of troubled families and either reproductive loss or loss of a parent. Ovarian stimulation of the donors followed our standard in vitro fertilization protocol. The recipients' exogenous steroid replacement continued until days 97 and 101, respectively, of the two gestations. Both pregnancies resulted in the delivery of normal singleton males--the first at 40 weeks, the second at 35 weeks.
Stromal cells derived from proliferative or secretory human endometria, cultured in the absence of steroid hormones, grew as monolayers that showed only occasional areas of immunoreactive fibronectin and did not produce detectable levels of prolactin (PRL) or laminin. Treatment with physiological doses of estradiol and progesterone induced PRL production and stimulated cell proliferation, resulting in multilayering with an increase of the saturation density. Electron microscopy showed the development of gap junctions, whereas immunofluorescence revealed a dense pericellular matrix containing fibronectin and laminin. These findings show that human endometrial stromal cells in culture respond to physiological doses of ovarian hormones with ultrastructural, proliferative, and biochemical changes that are characteristic of decidualization in vivo. This culture system thus provides an in vitro model for human decidualization.
We have performed surgical transections on nerves in the transforming claws of snapping shrimps. In normal transformation muscle restructuring occurs, involving degeneration of some fibers and biochemical changes in others. Surgical section of the entire second limb nerve root or of its distal, dorsal branch--both of which contain the motor axons to the closer muscle--prevents muscle restructuring, even though transformation of external claw morphology proceeds. Furthermore, nerve lesions must be performed within a specific time period after transformation has been triggered in order for the effects to be observed. We suggest that transformation involves an early sensitization of the targeted muscle and that this process depends upon an intact nervous pathway within the second nerve root.
Ultrasonic techniques have been developed as alternatives to conventional laparoscopic aspiration for oocyte retrieval for in vitro fertilization (IVF). Given the advantages (less risk, lower cost, and greater patient acceptance) of these alternative techniques, it is appropriate to assess their efficacy compared with traditional laparoscopic retrieval. This article examines the recovery rate of oocytes and their subsequent fertilization rate with the use of an ultrasonic endovaginal transducer with fixed needle guide and compares these results with other retrieval methods. Comparisons were made between laparoscopic harvesting (n = 71, group I), ultrasonic transabdominal transvesical (n = 21, group II), and ultrasonic vaginal transducer (n = 76, group III). The data demonstrate comparable success using an ultrasonic endovaginal transducer with fixed needle guide. The authors believe this technique to be the procedure of choice for all routine oocyte retrievals during IVF treatment.
Patients beginning an in vitro fertilization (IVF) treatment cycle were prospectively randomized in double-blind fashion to receive either follicle-stimulating hormone (FSH) (Metrodin, Serono Laboratories, Inc., Randolph, MA) (n = 50) or human menopausal gonadotropin (hMG) (Pergonal, Serono) (n = 48) in combination with clomephene citrate (CC) (Serophene, Serono). There were no statistically significant differences in the percentage of dropped cycles, follicular response as measured by serum estradiol or ultrasound imaging, cycle day for hCG administration, number of oocytes recovered, fertilization and cleavage rates of the recovered oocytes, or the rate of clinical pregnancy establishment. In conclusion, there were no clinically important differences between FSH and hMG when combined with CC for enhanced follicular recruitment for IVF. Therefore, there is no apparent justification for the use of FSH in CC combination regimens, considering FSH's increased cost as compared with hMG.
Ovulatory dysfunction is a leading cause of female infertility in the United States. Fortunately, ovulatory dysfunction is often amenable to treatment. Thorough testing is necessary to identify the exact cause of anovulation before conventional ovulation-inducing therapy is started. Careful patient monitoring is essential to avoid risks such as the ovarian hyperstimulation syndrome. Several newer ovulation-inducing agents are available for use in special situations.
Induction of ovulation is difficult to achieve in patients with PCOD when they are resistant to therapy with clomiphene citrate; moreover, treatment with human menopausal gonadotropins subjects the PCOD patient to the risk of multifollicular ovulation and hyperstimulation. This article summarizes the hormonal picture and the initial therapeutic approach to the patient with PCOD. The proper administration, usage, and monitoring of conventional ovulation-inducing agents for these patients are discussed. Some of the newer approved agents that can be used in special patients who have not responded to conventional ovulation induction are also described.