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Biomedical subjects

R J Paulson

Publications and source records attributed to R J Paulson.

At least 19 recordsLinked to original sources

Endocrine and clinical effects of micronized estradiol administered vaginally or orally.

OBJECTIVE: To determine the impact of the vaginal route of micronized estradiol (E(2)) administration upon hepatic globulin and lipid production and upon the outcome of oocyte donation cycles in which the recipients received E(2) via this route. DESIGN: Series report. SETTING: University-based assisted reproduction techniques (ART) program. PATIENT(S): Recipients of donor oocytes. INTERVENTION(S): Administration of micronized E(2) via the oral or vaginal route, oocyte donation, and embryo transfer. MAIN OUTCOME MEASURE(S): Measurements of the serum levels of free E(2), sex hormone-binding globulin (SHBG), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), as well as endometrial thickness and pregnancy outcome. RESULT(S): Serum SHBG and lipoprotein levels were unaltered by the vaginal as compared with the oral route of E(2) administration. Serum free E(2) levels were significantly higher after vaginal administration. Ten patients who had previously failed to achieve adequate endometrial thickness with an oral regimen were found to have adequate endometrial thickness after vaginal E(2) administration and seven of them achieved an ongoing pregnancy after embryo transfer. CONCLUSION(S): Vaginal administration of micronized E(2) results in significantly higher free serum E(2) levels when compared to levels achieved after oral E(2) administration. Hepatic globulin and lipoprotein production is similar despite 10-fold higher serum E(2) levels after the vaginal administration. The greater efficiency of E(2) delivery to the endometrium after vaginal administration makes this route a good option for patients who fail to achieve adequate endometrial thickness with oral E(2) administration.

Administration, Intravaginal↗

A prospective randomized trial comparing clomiphene citrate with tamoxifen citrate for ovulation induction.

OBJECTIVE: To compare the rates of ovulation and pregnancy after tamoxifen citrate (TMX) or clomiphene citrate (CC) among anovulatory women with infertility. DESIGN: Prospective randomized trial. SETTING: Infertility clinic in a university teaching hospital. PATIENT(S): Eighty-six anovulatory women under 40 years of age undergoing ovulation induction. INTERVENTION(S): The women were assigned randomly to receive either TMX or CC on cycle days 5-9. MAIN OUTCOME MEASURE(S): Rates of ovulation and pregnancy for the two treatment modalities. RESULTS(S): The overall rate of ovulation in the TMX group was 50 of 113 (44.2%) and in the CC group, 41 of 91 (45.1%). There were 10 pregnancies in the TMX group and 6 pregnancies in the CC group. The cycle fecundity per ovulatory cycle was 20.0% in the TMX group and 14.6% in the CC group. CONCLUSION(S): The overall rate of ovulation and pregnancy were similar with TMX and CC. TMX is a suitable alternative agent to CC in the management of anovulatory infertility.

Adult↗

Is there evidence for preferential delivery of ovarian estradiol to the endometrium?

OBJECTIVE: To determine the direction of delivery of E(2) in the female pelvis by assessing the ratio of endometrial to serum E(2) in women whose ovaries were stimulated to produce E(2) with women who received exogenous E(2). DESIGN: Prospective comparative study. SETTING: University-based ART program. PATIENT(S): Oocyte donors and recipients of donor oocytes. INTERVENTION(S): Micronized E(2) administered by the oral or vaginal route and oocyte donation. MAIN OUTCOME MEASURE(S): Serum and endometrial levels of E(2). RESULT(S): Serum E(2) levels were significantly higher in women who underwent controlled ovarian hyperstimulation (COH) and women receiving exogenous E(2) by the vaginal route than in those who received oral E(2). Levels of E(2) in endometrial tissue were similar in women who underwent COH and those receiving oral E(2). Endometrial E(2) levels in women who underwent vaginal administration were significantly higher than those in the oral E(2) or COH groups. The ratio of endometrial to serum E(2) was highest in women who underwent vaginal E(2) and lowest in those undergoing COH. CONCLUSION(S): Vaginal administration of micronized E(2) results in preferential absorption of E(2) into the endometrium, consistent with a "uterine first pass" effect. Since endogenous E(2) produced the smallest ratio of E(2) between the endometrium and serum, E(2) produced by the ovaries is not preferentially delivered to the uterus.

Administration, Oral↗

Pregnancy rates following fimbriectomy reversal via neosalpingostomy: a 10-year retrospective analysis.

OBJECTIVE: To establish parameters associated with successful fimbriectomy reversal and to estimate monthly fecundability and cumulative pregnancy rates through life-table analysis. DESIGN: Series report. SETTING: University-based infertility clinic. PATIENT(S): Forty-one women undergoing surgery for tubal sterilization reversal. INTERVENTION(S): Surgical fimbriectomy reversal. MAIN OUTCOME MEASURE(S): Time from sterilization to reversal, laparoscopy vs. laparotomy, uni- vs. bilateral fimbriectomy reversal, Bruhat vs. suture, tubal lengths, postsurgical hysterosalpingogram, ovulation induction, incidence of pregnancy and outcome, and life-table analysis to determine pregnancy rate. RESULT(S): The mean time from sterilization to reversal was 11.5 years. Of the 41 women who underwent fimbriectomy reversal, 6 (14.6%) conceived. Sixteen reversals were performed by laparotomy resulting in 4 (25%) pregnancies, whereas 25 were performed laparoscopically resulting in 2 (8%) pregnancies. Eight had unilateral salpingostomies and 33 bilateral, of which 1 of 8 (12.5%) and 5 of 33 (15.2%) conceived, respectively. Using the Bruhat technique, 1 of 11 (9%) conceived vs. 5 of 30 (16.7%) that underwent reversal using sutures. The mean postoperative tubal length for the 6 women who conceived was 8 cm vs. 6.7 cm in the 35 women who did not conceive. Postoperatively, 26 women received ovulation induction and 1 (3.8%) conceived whereas 5 (33.3%) conceptions occurred in 15 women who did not require ovulation induction. Using life-table analysis with 619 postsurgical cycles, the monthly fecundability was.0097. The cumulative conception rate after 5 years was 31.2%. CONCLUSION(S): Neosalpingostomy for the reversal of fimbriectomy sterilization represents a viable option for fertility restoration. The best candidates for this procedure are spontaneously ovulatory and have a tubal length of more than 7 cm.

Adult↗

Altered balance between the 5 alpha-reductase and aromatase pathways of androgen metabolism during controlled ovarian hyperstimulation with human menopausal gonadotropins.

PURPOSE: To evaluate androgen production and metabolism during controlled ovarian hyperstimulation. METHODS: Five women, aged 33-42, were studied. All participants were undergoing controlled ovarian hyperstimulation with gonadotropin-releasing hormone agonist and human menopausal gonadotropins. Serum estradiol, estrone, androstenedione, testosterone, 3 alpha-androstanediol glucuronide, and sex hormone-binding globulin levels were measured at 6 time points during the cycle. RESULTS: The levels of all steroids increased significantly from baseline during controlled ovarian hyperstimulation. Mean total testosterone levels increased from 0.29 +/- 0.05 ng/mL to 0.58 +/- 0.07 ng/mL after gonadotropin stimulation. Sex hormone-binding gonadotropin levels increased from 50 +/- 16 nM to 73 +/- 12 nM after gonadotropin stimulation. Estrone/androstenedione and estradiol/testosterone ratios, reflecting the aromatase pathway, increased whereas 3 alpha-androstanediol glucuronide/androstenedione and 3 alpha-androstanediol glucuronide/testosterone ratios, reflecting 5 alpha-reductase activity, decreased. CONCLUSIONS: Controlled ovarian hyperstimulation with human menopausal gonadotropins results in increased serum testosterone and androstenedione levels. Whereas there is an enhancement in androgen metabolism by aromatase, 5 alpha-reductase activity with regard to androgen metabolism is diminished.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

The prognostic significance of day 3 embryo cleavage stage on subsequent blastocyst development in a sequential culture system.

PURPOSE: To determine prognostic significance of blastomere number on Day 3 of culture upon subsequent blastocyst (BL) development. METHODS: A retrospective analysis was conducted in 37 IVF subjects undergoing standard protocols and BL transfer after sequential embryo culture in P1 and BL media. RESULTS: Of Day 3 embryos containing 7 or more blastomeres, 68.9% (186/270) developed into BL compared to embryos containing 4-6 blastomeres, 38.1% (56/147), P < 0.0001. The majority of BL, 68.9% (168/244), were observed on Day 5. Extended Day 6 culture represented 31.1% (76/244) of all BLs. CONCLUSIONS: The observation of 7 or more blastomeres on Day 3 yielded a significantly greater likelihood of BL development. Embryos containing 4-6 blastomeres are still relatively likely to progress to a BL. Extended culture to Day 6 still yields a significant proportion of BL. Cell cleavage stage on Day 3 appears to be a useful prognostic indicator of subsequent BL development.

Adult↗

The lack of influence of age on male fertility.

OBJECTIVE: This study was undertaken to determine the effect of male aging on sperm quality as determined by semen analysis, the fertilization rate of human oocytes in vitro, and live birth rates. STUDY DESIGN: Retrospective analysis correlating outcome measures with male age was performed for 558 oocyte donation cycles in 441 couples. The oocyte donation model was chosen because it controls for oocyte quality and endometrial receptivity, which allows variations in sperm quality as a function of male age to be the only dependent variable. Outcome measures analyzed were semen analysis, fertilization rates in vitro, pregnancy rates, live birth rates, and cumulative live birth rates by life-table analysis. RESULTS: There was a negative correlation between male age and total sperm count, but there was no correlation between male age and any of the other parameters in the semen analysis. There was no association between male age and the fertilization rate of donated oocytes in vitro, pregnancy rates, or live birth rates. Recipient couples were grouped by quartiles of male age, and cumulative live birth rates were the same in the 4 groups. CONCLUSION: Whereas male aging is associated with a significant decline in total sperm count, this change is not reflected in a decreased fertilization rate or a decreased live birth rate in the oocyte donation model.

Adult↗

Comparison of estrogen and androgen levels after oral estrogen replacement therapy.

OBJECTIVE: To assess the extent of accumulation of circulating estrone (E1), total and free estradiol (E2) and estrone sulfate (E1S) levels in postmenopausal women receiving prolonged oral E2 therapy and to determine the effect of increased estrogenicity on free testosterone levels. STUDY DESIGN: Descriptive study involving 14 healthy postmenopausal women during a three-year period. Group 1 (n = 7) took a placebo. Group 2 (n = 7) took 1 mg micronized E2 daily. Blood samples were taken at one, two and three years. E2, E1 and total testosterone were quantified by radioimmunoassay (RIA) following extraction and celite chromatography. Free testosterone and E2 were calculated. Sex hormone-binding globulin (SHBG) and E1S were quantified by RIA. RESULTS: In the control group, none of the hormone levels changed significantly. Free testosterone decreased 49% in women taking E2 replacement as compared to a 7% decline in women taking placebo. In women taking E2 replacement, E1, E2, E1S, free E2 and SHBG levels increased 10, 6, 51, 2 and 2 times, respectively, between baseline and year 3. CONCLUSION: E1, E2 and E1S levels significantly increased with E2 replacement. Free testosterone levels decreased with E2 replacement. Testosterone replacement may be warranted when giving postmenopausal women estrogen replacement therapy.

Administration, Oral↗

Antiphospholipid antibodies and in vitro fertilization success: a meta-analysis.

OBJECTIVE: To evaluate whether the presence of antiphospholipid antibodies among women undergoing IVF affects the likelihood of IVF success. DESIGN: A meta-analysis of seven eligible studies on antiphospholipid antibodies and IVF outcome. MAIN OUTCOME MEASURE(S): Odds ratios (ORs) and 95% confidence intervals (CIs) of an association between the presence of antiphospholipid antibodies and both clinical pregnancy and live birth from IVF. RESULT(S): There was no significant association between antiphospholipid abnormalities and either clinical pregnancy (OR 0.99; 95% CI 0.64-1.53) or live birth (OR 1.07; 95% CI 0.66-1.75) in IVF patients. CONCLUSION(S): The measurement of antiphospholipid antibodies is not warranted in patients undergoing IVF.

Autoantibodies↗

Comparison of two methods for the measurement of sperm concentration.

OBJECTIVE: To determine the accuracy of both the hemocytometer and the MicroCell, to evaluate which method is the most reliable, and to confirm the accuracy of latex beads as an internal standard. DESIGN: Prospective procedural assessment. SETTING: University-based infertility clinic. PATIENT(S): One hundred sixty-five male sexual partners of women undergoing screening for infertility. INTERVENTION(S): Semen analysis. MAIN OUTCOME MEASUREMENT(S): Sperm and latex bead concentrations. RESULT(S): Sperm concentration values obtained with the hemocytometer were highly correlated with those obtained from the MicroCell (r = 0.88). The mean value of the latex beads concentration was closer to the standard value using the hemocytometer than the MicroCell. CONCLUSION(S): Both the hemocytometer and the MicroCell are suitable as screening techniques to measure sperm concentration. Fixed suspensions of latex beads serve as reliable internal quality control standards.

Cytological Techniques↗

Serum and tissue hormone levels of vaginally and orally administered estradiol.

OBJECTIVE: Our purpose was to determine serum and endometrial estradiol levels when micronized estradiol is administered vaginally and orally. STUDY DESIGN: Five subjects were given oral estradiol (2 mg twice daily), during an artificial luteal phase, and another group of 5 subjects were given the same dose of estradiol by the vaginal route. Endometrial biopsies and blood samples were obtained on day 21 of the cycle, 2 hours after the last dose was administered. Tissue and blood samples were assayed for estradiol. RESULTS: Serum estradiol levels were significantly higher with vaginally administered estradiol than with orally administered estradiol (2344 +/- 398 vs 279 +/- 76 pg/mL, P <.005). Endometrial estradiol concentrations were also significantly higher with vaginally administered estradiol than with the oral preparation (918 +/- 412 vs 13 +/- 2 pg/mg protein, P <.05). CONCLUSIONS: Vaginal administration of estradiol is more effective in increasing serum and endometrial levels of estradiol than the oral route and may represent the optimal route of administration for recipients of egg donation. If the vaginal route of estradiol administration is considered for menopausal replacement therapy, much lower doses of the standard oral quantities should be used. Furthermore, if the uterus is present, a progestin must be used to compensate for the high tissue levels of estradiol.

Administration, Intravaginal↗

Increased angiotensin-converting enzyme activity in a patient with severe ovarian hyperstimulation syndrome.

OBJECTIVE: To assess plasma angiotensin-converting enzyme (ACE) activity in a patient with severe ovarian hyperstimulation syndrome (OHSS). DESIGN: Case report. SETTING: Private, university-affiliated infertility practice. PATIENT(S): A 35-year-old woman with OHSS. INTERVENTION(S): Clomiphene citrate induction of ovulation. MAIN OUTCOME MEASURE(S): Plasma ACE activity. RESULT(S): The patient had a brain stem infarction as a result of thrombosis caused by severe OHSS. Plasma ACE activity was significantly elevated and persisted long after resolution of the OHSS. CONCLUSION(S): Elevated ACE activity appears to have been associated with the development of OHSS in this patient. Further study of the ovarian renin-angiotensin system in the development of OHSS is warranted.

Adult↗

Immature oocyte retrieval: lessons from unstimulated IVF cycles.

OBJECTIVE: To describe retrieval of immature oocytes during unstimulated IVF and assess the in vitro maturation and fertilization rates. DESIGN: Retrospective analysis. SETTING: The USC program for assisted reproduction. PATIENT(S): Spontaneously ovulatory women with predominantly pelvic factor as their principal cause of infertility, under the age of 40, and no male factor. INTERVENTION(S): HCG administration in mid-cycle, aspiration of all visible follicles, in vitro maturation of immature oocytes in culture media versus 50% follicular fluid in media, IVF, and embryo transfer. MAIN OUTCOME MEASURE(S): Rates of in vitro maturation, fertilization, and implantation after embryo transfer. RESULT(S): A total of 101 immature oocytes were obtained during 59 follicle aspirations. Thirty percent of prophase I oocytes matured to metaphase II in vitro compared with 44% of metaphase I oocytes. Fertilization rates for matured prophase I oocytes were 62% for those cultured in standard culture media (controls) and 87% for follicular fluid culture media. Two pregnancies resulted from the transfer of embryos derived from immature oocytes when no other embryos were transferred. CONCLUSION(S): Immature oocytes may be retrieved successfully during the mid-cycle aspiration of the dominant follicle in unstimulated IVF cycles. Maturation of immature oocytes in vitro with follicular fluid results in similar maturation and fertilization rates as for control incubation. Immature oocytes thus retrieved contribute to the overall pregnancy success of unstimulated IVF cycles. It may be better to retrieve immature oocytes during unstimulated cycles than during the follicular phase of natural cycles.

Cellular Senescence↗

Resolution of hormonal markers of ectopic gestation: a randomized trial comparing single-dose intramuscular methotrexate with salpingostomy.

OBJECTIVE: To evaluate resolution of serum hCG and progesterone in patients with ectopic pregnancy receiving single-dose intramuscular (IM) methotrexate as compared with those undergoing laparoscopic salpingostomy. METHODS: In this prospective randomized clinical trial, 75 hemodynamically stable women with a diagnosis of ectopic pregnancy were randomized to treatment with single-dose IM methotrexate (1 mg/kg) or laparoscopic salpingostomy. All women had initial, day 4, and weekly serum hCG and progesterone measurements taken until hCG levels were less than 15 mIU/mL. Methotrexate therapy was repeated if posttreatment day 7 hCG levels did not decrease by 15%, as compared with day 4 levels. Success rate was defined as ectopic resolution without the need for the alternate mode of therapy. RESULTS: Thirty-eight women were randomized to treatment with methotrexate and 37 to laparoscopic salpingostomy. The mean (+/-standard deviation) time required for serum progesterone concentrations to decrease to less than 1.5 ng/mL was significantly less for laparoscopic salpingostomy than for treatment with methotrexate: 7.8+/-1.7 and 17.6+/-2.2 days, respectively (P < .01). Within each treatment group, serum progesterone levels resolved (less than 1.5 ng/mL) more rapidly than did hCG levels (less than 15 mIU/mL) (P < .01). No further treatment was required once serum progesterone levels had decreased to less than 1.5 ng/mL. Success rates were similar in both groups: 94.7% (36 of 38) for methotrexate and 91.4% (33 of 36) for laparoscopic salpingostomy. Mean time required for hCG concentrations to decrease to less than 15 mIU/mL was significantly less for laparoscopic salpingostomy than for methotrexate therapy: 20.2+/-2.7 and 27.2+/-2.3 days, respectively (P < .05). Additional methotrexate injections were required in 15.8% (6 of 38) of women randomized to methotrexate therapy. Initial serum hCG levels for patients receiving additional methotrexate doses were 4830+/-1588 mIU/mL as compared with 2133+/-393 mIU/mL for women receiving only one dose (P = .07). CONCLUSION: Serum progesterone levels of less than 1.5 ng/mL are a good predictor of ectopic pregnancy resolution regardless of treatment, and because its return to normal values occurs more rapidly than that of hCG levels, serum progesterone may be a better marker for predicting successful treatment. Although laparoscopic salpingostomy leads to faster resolution of hormonal markers of ectopic gestation, methotrexate is equally successful for treating small unruptured ectopic pregnancies. Initial hCG levels may be a marker for women requiring additional doses of methotrexate.

Abortifacient Agents, Nonsteroidal↗

Factors influencing sperm-zona pellucida binding in vitro using the intact zona model.

The zona pellucida binding assay assesses the ability of spermatozoa to bind to the zona pellucida. The present study investigated the influence of: (i) prior oocyte exposure to spermatozoa on subsequent sperm-zona pellucida binding in vitro; and (ii) cryopreservation of oocytes. Only oocytes obtained from fertile donors were used and the binding capacity of non-inseminated, cryopreserved oocytes was compared with both inseminated/unfertilized, cryopreserved oocytes and inseminated/unfertilized, non-cryopreserved oocytes recovered from in-vitro fertilization cultures on sperm-zona pellucida binding using an intact zona model. There was no statistically significant difference in sperm-zona binding between non-inseminated, cryopreserved oocytes (range 9.6-23.2), inseminated/unfertilized, cryopreserved oocytes (range 15.0-16.0) and inseminated/ unfertilized, non-cryopreserved oocytes (range 3.3-23.0). The coefficient of variation for sperm binding to all oocyte groups was very large (range 37-121%). We conclude that neither prior exposure of human oocytes to human spermatozoa nor cryopreservation of human oocytes influences the subsequent binding of a different population of spermatozoa to the zona pellucida. However, large oocyte-to-oocyte variation of sperm-zona binding may diminish the usefulness of this assay in clinical practice and as a research tool.

Cryopreservation↗