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Biomedical subjects

R F Casper

Publications and source records attributed to R F Casper.

At least 109 records · Page 6Linked to original sources

The response to ovarian hyperstimulation and in-vitro fertilization in women older than 35 years.

There are conflicting reports concerning the effect of female age and potential reproductive function. We assessed the response to ovarian hyperstimulation in two consecutive IVF cycles in 25 women greater than 35 years of age and compared their response to a control group of 48 women less than 35 years of age who conceived in our IVF programme. In the older women, the maximal oestradiol response was proportional to the number of vials of HMG used and did not differ from the response of the younger women. Similarly, the number of follicles of diameter greater than 1.0 cm, the number of oocytes recovered and the number of embryos which cleaved did not differ between the older and the younger women. However, conception rates were markedly lower in the older women than the overall pregnancy rate in the IVF programme during the same time period. We conclude that the older women in this study have a normal response to ovarian stimulation but may have a decreased receptivity of the endometrium or increased numbers of embryos with chromosomal abnormalities, leading to a reduced rate of implantation.

Clomiphene↗

Sonographic determination of a possible adverse effect of clomiphene citrate on endometrial growth.

We recently demonstrated, using transvaginal sonography, that conception cycles in in-vitro fertilization (IVF) are associated with a significantly thicker endometrium at midcycle than non-conception cycles, suggesting that endometrial growth may influence implantation. In the present study, to examine whether the type of stimulation protocol affects endometrial development, we compared the sonographic appearance of the endometrium in 22 patients randomized to receive clomiphene citrate and human menopausal gonadotrophin (CC/HMG) and in 19 who received HMG alone. A significantly thicker endometrium was observed in the HMG patients compared to the CC/HMG group (P less than 0.005) throughout the follicular phase of the cycle, although serum concentrations of oestradiol (E2) did not differ in the two groups. Twenty-three patients (13 in the HMG group and 10 in the CC/HMG group) had previous IVF cycles with CC/HMG stimulation in which endometrial thickness was measured. A thin endometrium recurred with subsequent CC/HMG cycles while increased growth occurred with HMG only compared to previous CC/HMG cycles. Therefore, ultrasound examination of the endometrium in this study demonstrated that CC results in a thinner endometrium than HMG alone. We believe these findings may be of importance in improving pregnancy rates in IVF and possibly in other infertility therapy which involves the use of clomiphene citrate.

Clomiphene↗

Use of gonadotropin-releasing hormone agonist to trigger follicular maturation for in vitro fertilization.

In spontaneous cycles both LH and FSH are secreted in a surge at midcycle. In in vitro fertilization (IVF) cycles, hCG administration results in elevation of LH-like activity only. The objective of this study was to compare the effectiveness of a single midcycle dose of GnRH agonist with hCG on follicular maturation. Eighteen IVF cycles in 14 women were randomized to receive either 0.5 mg leuprolide acetate or 5000 IU hCG at midcycle. Both groups underwent identical ovarian stimulation and cycle monitoring. On the day of GnRH agonist or hCG administration, estradiol concentrations and the number of follicles 1.5 cm or larger were the same in both groups. Mean serum LH and FSH levels were elevated for 34 h after GnRH agonist administration. In contrast, mean serum hCG levels were elevated for approximately 6 days after the administration of hCG, and serum FSH levels did not change. Mean luteal phase serum estradiol concentrations were lower in the GnRH agonist group than in the hCG group (P less than 0.02). No differences were observed in mean serum progesterone or PRL during the luteal phase or in the length of the luteal phase in the two groups. The mean number of oocytes retrieved and embryo number and quality did not differ between the two groups. Three of nine GnRH agonist cycles and none of nine hCG cycles resulted in clinical pregnancy (P = 0.1). The results of this study indicate that GnRH agonist is able to simulate a midcycle surge of gonadotropins, leading to follicular maturation and pregnancy. Further work is needed to determine whether there is any clinical advantage of GnRH agonist over hCG administration with regard to pregnancy rates.

Adult↗

Transvaginal ultrasound in selective embryo reduction for multiple pregnancy.

Ovulation induction for the treatment of infertility is known to carry the risk of inducing multiple gestations, with attendant high perinatal morbidity and mortality. Selective reduction of the number of fetuses in a multiple gestation to reduce this risk, using transvaginal ultrasound, is a recent technological development. Six patients (three with quadruplets and three with triplets) underwent selective embryo reduction in the first trimester using real-time transvaginal ultrasound. Potassium chloride was used for intrathoracic injection. One of the procedures was complicated by chorioamnionitis 48 hours later, necessitating termination of pregnancy. Transvaginal sonographically directed selective reduction represents an important addition to the management of unplanned multiple pregnancy resulting from infertility treatment. The procedure is not without risks, and these must be weighed against potential benefits.

Abortion, Induced↗

Rates and outcome of pregnancies achieved in the first 4 years of an in-vitro fertilization program.

Between Feb. 1, 1984, and Dec. 31, 1987, 578 couples were treated in the in-vitro fertilization (IVF) program at University Hospital, London, Ont. The 160 confirmed pregnancies resulted in 86 deliveries and the birth of 108 babies. There were 20 spontaneous abortions, 12 ectopic pregnancies, 11 presumptive pregnancies, 4 neonatal deaths and 1 stillbirth. At the time of writing, 41 pregnancies of 20 weeks' gestation or more were in progress. Except for a high cesarean section rate the obstetric outcome of pregnancies achieved with IVF does not appear to be different from that expected for a group of infertile couples treated with conventional therapies. The pregnancy rates varied according to the denominator used.

Abortion, Spontaneous↗

The influence of transient hyperprolactinemia on hormonal parameters, oocyte recovery, and fertilization rates in in vitro fertilization.

A detrimental effect of transient elevation of plasma prolactin (PRL) during in vitro fertilization (IVF) has not been proven; however, treatment with a dopamine agonist has been suggested. The present study was undertaken to determine if transient, midcycle hyperprolactinemia exerted a deleterious effect on the number of oocytes retrieved or on fertilization of oocytes in vitro. Fifty-three infertile patients with midcycle hyperprolactinemia (PRL greater than 20 micrograms/liter) during ovarian hyperstimulation for IVF were compared with 53 matched controls who remained normoprolactinemic. Mean (+/- SE) serum PRL levels on the day after hCG were significantly higher in the study group (29.5 +/- 1 micrograms/liter) than in the control (13.1 +/- 0.5 microgram/liter) (P less than 0.0005), whereas the mean estradiol (E2) concentrations on the same day were not significantly different (4822 +/- 287 and 4492 +/- 269 pmol/liters, respectively). Fertilization rates (72 +/- 4 and 70 +/- 4%, respectively) and the mean number of oocytes recovered (4.2 +/- 0.3 and 3.7 +/- 0.3, respectively) did not differ between the two groups. No correlation was observed between serum PRL and E2 levels, fertilization rates, or the number of oocytes retrieved in either group. Eleven patients with elevated PRL levels as a result of ovarian hyperstimulation were treated with 2.5 mg bromocriptine daily during the next IVF cycle. Serum PRL levels were significantly lower in the treated (5.6 +/- 1.8 micrograms/liter) than in the untreated cycles (35.6 +/- 3.1 micrograms/liter) (P less than 0.0005), whereas serum E2 concentrations did not differ.(ABSTRACT TRUNCATED AT 250 WORDS)

Bromocriptine↗

Characterization of pure human first-trimester cytotrophoblast cells in long-term culture: growth pattern, markers, and hormone production.

Pure long-term cytotrophoblast cultures were established from human first-trimester placentas by growing chorionic villus explants without enzymatic digestion. Cytoplasmic human chorionic gonadotropin was detectable in all (100%) cells in culture when labeled with a polyclonal anti-human chorionic gonadotropin antibody and in 71% to 83% of cells labeled with a monoclonal anti-alpha-human chorionic gonadotropin antibody. Most of the cells expressed cytokeratin and surface Trop-1 and Trop-2 antigens (89% to 95%), but none expressed cytoplasmic vimentin or surface 63D3 antigens. Study of the ultrastructure of the cells demonstrated epithelial morphologic features. The average doubling time of the trophoblast was 48 to 96 hours. Some of the lines have been continuously propagated for 8 months. They produced variable amounts of human chorionic gonadotropin (50 to 710 mIU/ml per 10(5) cells per 24 hours). The basal level of progesterone secreted by trophoblast (444.4 +/- 32.4 pg/ml per 10(5) cells per 24 hours) doubled in the presence of pure human chorionic gonadotropin (100 ng/ml). They produced small amounts of 17 beta-estradiol (less than 20 pg/ml per 10(5) cells per 24 hours); human chorionic gonadotropin had no effect on the estradiol production. Trophoblast-derived human chorionic gonadotropin acted as a growth factor because trophoblast proliferation (measured by uptake of thymidine labeled with tritium) was reduced by 60% in the presence of an anti-human chorionic gonadotropin antibody. Availability of pure, functionally competent human cytotrophoblast in long-term cultures is relevant for further studies in reproduction biology.

Antigens↗

Assessment of experienced pain associated with transvaginal ultrasonography-guided oocyte recovery in in vitro fertilization patients.

We described a study designed to assess the pain experienced by in vitro fertilization patients undergoing transvaginal ultrasonography-guided oocyte recovery. Participants were 164 women who underwent 194 oocyte recovery procedures at a university teaching hospital. Measurements of the intensity of pain and the quality of pain were obtained immediately after the procedure and again 1 hour later. Results show that the majority of patients reported manageable levels of discomfort, and that there was a marked reduction in both intensity and qualitative complexity over time, which suggests there were minimal residual effects. Repeated measures analyses of data from participants who underwent the procedure on two occasions suggest that familiarity with the procedure has no effect on reported pain. Finally, patients' levels of pain correlated significantly with several psychological self-report measures.

Adult↗

Unexplained infertility: evaluation of treatment with clomiphene citrate and human chorionic gonadotropin.

A double-blind, randomized, prospective therapeutic trial was conducted in 148 couples with unexplained infertility. Treatment consisted of 4 consecutive months of placebo or clomiphene citrate (CC) (100 mg) by mouth on cycle days 5 to 9, and placebo or human chorionic gonadotropin (hCG) (5,000 IU) intramuscularly on cycle days 19, 22, 25, and 28. There were 14 pregnancies during the trial and 39 pregnancies during observation before and after the trial. Placebo treatment resulted in no pregnancies over 4 months. Clomiphene citrate was significantly better than placebo (P less than 0.04), with a pregnancy rate of 19% over the course of 4 months. The pregnancy rate with hCG either alone (11%) or in combination with CC (7.6%), was not significantly better than placebo. Treatment-independent pregnancies, defined as those before treatment (but after enrollment), or more than 1 month after therapy, occurred in 16% of the couples, with a mean time to conception of 8.8 months. As part of their follow-up, 39 of the study couples subsequently underwent in vitro fertilization (IVF), and 43% were found to have a previously unrecognized male factor or fertilization defect. A pregnancy rate of 16% was achieved after a mean of 1.1 cycles in these 39 couples. The authors conclude that CC is useful in treating unexplained infertility and is a reasonable initial therapy. For couples who fail to conceive, IVF may be diagnostic as well as therapeutic.

Adult↗

Does transient hyperprolactinemia during ovarian hyperstimulation interfere with conception or pregnancy outcome?

The significance of transiently increased serum prolactin (PRL) levels on pregnancy rates in in vitro fertilization (IVF) is unknown. The aim of this study was to evaluate PRL levels in IVF patients who conceived and in matched controls who did not. Thirty-seven IVF cycles resulting in pregnancy and 74 nonpregnant cycles were compared. Prolactin was measured before ovarian stimulation with clomiphene citrate, and human menopausal gonadotropin and estradiol (E2) and PRL were measured 8 hours after human chorionic gonadotropin (hCG) administration at midcycle. Before ovarian stimulation, serum PRL levels were not different in the pregnant and nonpregnant women (11.1 +/- 0.6 [mean +/- standard error] micrograms/l and 10.1 +/- 0.4 micrograms/l, respectively). After hCG, PRL levels were significantly higher in the pregnant women than in the nonpregnant women (20.8 +/- 1.6 and 16.0 +/- 0.9 micrograms/l, respectively; P less than 0.005) and more pregnant than nonpregnant women had elevated PRL levels (49% versus 28%, respectively; P less than 0.05). There was no correlation between PRL and E2 in either group. The abortion rate was not different between the women with elevated PRL (22.2%) and the normoprolactinemic women (31.6%). These results do not support treatment of transient hyperprolactinemia with dopamine agonists in IVF patients.

Chorionic Gonadotropin↗

Endometrial thickness and growth during ovarian stimulation: a possible predictor of implantation in in vitro fertilization.

The present study was undertaken to evaluate endometrial thickness and the amount of endometrial growth (delta) in patients who conceived during in vitro fertilization (IVF) (n = 36) compared with matched women who did not conceive (n = 72). Estradiol (E2) and endometrial thickness were measured daily from cycle day 10 to the day after human chorionic gonadotropin (hCG). Mean endometrial thickness and E2 levels on cycle day 10 did not differ. On the day before ovum retrieval, significantly thicker endometrium was observed in the pregnant than in the nonpregnant women (8.6 +/- 0.3 [SEM] and 7.1 +/- 0.3 mm, respectively; P less than 0.0005), whereas the mean E2 levels did not differ. The delta endometrial growth was greater in the women who conceived than in the nonpregnant group (4.3 +/- 0.2 and 2.5 +/- 0.2 mm, respectively; P less than 0.0005). The fertilization rate and serum E2 levels did not correlate with endometrial thickness nor with delta endometrial growth. Our data suggest that the amount of endometrial growth during ovarian hyperstimulation and the endometrial thickness on the day before oocyte retrieval deserve further study as possible predictive parameters for implantation.

Embryo Implantation↗

Thyrotropin and prolactin responses to thyrotropin-releasing hormone in premenstrual syndrome.

Recent reports of altered TSH responsiveness to its releasing hormone (TRH) in women with premenstrual syndrome (PMS) suggested that subclinical hypothyroidism may be responsible for the mood changes, such as depression, that occur in these women. In this study we measured basal and TRH-stimulated serum TSH and PRL levels in 15 women with PMS and in 19 age-matched normal women. The mean baseline serum TSH concentrations were similar in the 2 groups in both the follicular [normal, 1.3 +/- 0.2 (+/- SE); PMS, 0.9 +/- 0.2 mU/L] and luteal (normal, 1.1 +/- 0.2; PMS, 1.1 +/- 0.2 mU/L) phases of the cycle. The mean baseline serum PRL levels also were similar in the 2 groups in the follicular (normal, 16 +/- 2; PMS, 13 +/- 2 micrograms/L) and luteal (normal, 13 +/- 2; PMS, 14 +/- 2 micrograms/L) phases of the cycle. After TRH administration, peak serum PRL and TSH levels were reached at 15 and 30 min, respectively, and the response curves were virtually identical in the 2 groups in both phases of the cycle. One normal woman had elevated basal and TRH-stimulated TSH concentrations compatible with subclinical hypothyroidism, but had normal noncyclic scores on her prospective rating scales. Our findings suggest that PMS is not associated with thyroid dysfunction or abnormal PRL secretion and that thyroid hormone replacement therapy is not indicated in this condition.

Adult↗

Interleukin-1 stimulates human chorionic gonadotropin secretion by first trimester human trophoblast.

Interleukin-1 (IL-1) has been reported to stimulate LH, GH, ACTH, and TSH release from cultured pituitary cells. IL-1 also has been found to be secreted in significant amounts by placental macrophages. To determine the possible role of IL-1 within the placenta, we studied the effects of human recombinant IL-1 on hCG release by long term cultures of human first trimester trophoblast and the JAR (human choriocarcinoma) cell line. IL-1 in concentrations ranging from 10(-11)-10(-9) mol/L stimulated hCG release from trophoblast cultures. This stimulatory effect was not mediated by prostaglandin E2 (PGE2), as indicated by the inability of indomethacin to block this stimulation as well as a lack of IL-1 effect on PGE2 release by trophoblast cells. At these doses, IL-1 exerted no effect on hCG release by JAR cells. PGE2, when used in high concentrations (10(-6)-10(-5) mol/L), stimulated the release of hCG by the trophoblasts as well as by the JAR cells. Neither IL-1 nor PGE2 stimulated the proliferation, [3H]thymidine incorporation, or differentiation (syncytium formation) of trophoblast or JAR cells. These results suggest that IL-1 may be an important local regulator of hCG secretion by first trimester trophoblasts.

Cell Division↗

Transvaginal, ultrasound-guided oocyte retrieval for in vitro fertilization.

As compared to laparoscopic oocyte retrieval, the trans-vaginal, ultrasound-guided technique can be performed away from a formal operating room, without general anesthesia and its attendant risks and with a significant reduction in operating time. Performed under paracervical block and minimal analgesia, transvaginal, ultrasound-guided oocyte retrieval results in a fairly easily tolerated level of pain during the procedure and very minimal residual pain postoperatively. The mean number of oocytes retrieved, fertilization and embryo transfer rates, and clinical pregnancy rates are not significantly different between the two procedures. If bleeding occurs from the vaginal puncture site, it is easily controlled with pressure. In this study, postoperative pelvic infection occurred in three patients. The above advantages and associated reduction in cost achieved with the trans-vaginal, ultrasound-guided procedure make it the current method of choice for oocyte retrieval.

Embryo Transfer↗

Psychological correlates of differential infertility diagnosis in an in vitro fertilization program.

We describe a study designed to assess the role of infertility diagnosis in differentiating participants in an in vitro fertilization program on psychological variables. Three hundred forty-eight in vitro fertilization candidates representative of five diagnostic categories (tubal problems, endometriosis, male factor, multiple factors, and idiopathic) underwent psychological assessment before entering the in vitro fertilization program. Measures of personality functioning, depression, anxiety, social support, coping ability, and marital adjustment were obtained. Analyses revealed significant differences among diagnostic groups on several psychological measures. As well, candidates were categorized as having either organic or functional (idiopathic) infertility, and analyses revealed several differences between these two groups. Results suggest ways of providing individualized psychological support in vitro fertilization participants.

Adaptation, Psychological↗

The effect of dietary supplementation with fish oil fatty acids on surgically induced endometriosis in the rabbit.

As a means of assessing the effects of natural inhibition of cyclooxygenase enzymes on arachidonic acid metabolism in vivo, the authors supplemented the diet of 38 New Zealand white rabbits with fish oil containing eicosapentaenoic acid and docosahexaenoic acid (EPA/DHA) or olive oil (control). Endometriosis was surgically induced 10 days later using a previously described experimental technique. Peritoneal fluid PGE2 and PGF2-alpha concentrations were significantly lower in the EPA/DHA group versus controls (P less than 0.05, P = 0.05, respectively). Total endometrial implant diameter 8 weeks after induction of endometriosis was significantly smaller in the experimental group (3.1 +/- 0.2 cm) compared with the controls (4.0 +/- 0.3 cm) (P less than 0.03). The authors conclude that dietary supplementation with fish oil, containing the n-3 polyunsaturated fatty acids EPA and DHA, can decrease intraperitoneal PGE2 and PGF2-alpha production and retard endometriotic implant growth in this animal model of endometriosis.

Animals↗

In vitro fertilization: diurnal and seasonal variation in luteinizing hormone surge onset and pregnancy rates.

The authors studied 740 consecutive in vitro fertilization (IVF) cycles over a 3-year period to compare the results of cycles in which an endogenous luteinizing hormone (LH) surge occurred with cycles in which human chorionic gonadotropin (hCG) was administered for induction of follicular maturation. Clomiphene citrate (100 to 150 mg daily on cycle days 5 to 9) and human menopausal gonadotropin (hMG; 75 to 150 IU daily from cycle day 6) were used for stimulation. Embryo transfer (ET) occurred in 164 (81.2%) of the LH surge cycles and 452 (84%; P = not significant [NS] of the hCG cycles. The first urinary rise in LH was detected in the 6 or 9 A.M. collections in 78 (47.3%) of the LH surge cycles, a greater number (P less than 0.01) than expected if LH surge onset was random. A total of 107 pregnancies was achieved, for an overall pregnancy rate of 17.4% per ET. The pregnancy rate in the hCG-stimulated cycles was 13.9% per ET (63/452) and, in spontaneous LH surge cycles, was 28.8% (44/166; P less than 0.001). The spontaneous abortion rate was 9.1% in LH surge cycles, compared with 25.4% in hCG-triggered cycles (P less than 0.001). The result was a 2.4 times increase in live births for LH surge cycles compared with cycles in which hCG was administered. In this program, occurrence of an LH surge is a favorable event, associated with higher pregnancy and live birth rates than hCG-stimulated cycles, and usually occurring in the early morning, allowing oocyte retrieval during normal working hours.

Adult↗