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Biomedical subjects

R F Casper

Publications and source records attributed to R F Casper.

At least 19 recordsLinked to original sources
PubMed1992

Chromosome status of untransferred (spare) embryos and probability of pregnancy after in-vitro fertilisation.

Many spontaneous abortions are associated with chromosomal abnormality of the fetus. In in-vitro fertilisation (IVF) the chromosome status of untransferred ("spare") embryos and subsequent fate (pregnancy or not) of the transferred sibling embryos might be related. Since the spare and transferred embryos of a patient's cycle genetically are full siblings, the inherited chromosomal abnormalities in spare embryos have a 50% probability of also appearing in transferred embryos. We have tested whether chromosome analysis of spare embryos has predictive power for transferred embryos. 48 couples with a total of 437 embryos were selected because their spare embryos (1-4 per couple; 76 total) were successfully analysed for chromosome status. 16 patients became pregnant. These women produced a higher proportion of chromosomally normal spare embryos (9/24; 37.5%) than those who did not achieve pregnancy (1/52; 1.9%). The proportion of patients who had only normal embryos was significantly higher (p = 0.012) in the pregnant group than in the non-pregnant group, and the proportion of patients who had only abnormal embryos was significantly higher (p = 0.001) in the non-pregnant group. Patients with preclinical and clinical pregnancy losses had only chromosomally abnormal spare embryos; by contrast, 50% of spare embryos from patients with ectopic pregnancies were normal. The proportion of spare embryos that were normal (13%, 10/76), was similar to the livebirth rate of 11% per transferred embryo (19 infants from 171 transferred embryos). These results suggest that chromosome analysis of spare embryos may have predictive value for their transferred sibling embryos. We conclude that improving detection of chromosomally normal embryos for transfer should improve the success rate in IVF.

Chromosome Aberrations↗
PubMed1992

Cytogenetics of human oocytes, zygotes, and embryos after in vitro fertilization.

Chromosome errors, inherited or arising de novo during gametogenesis and transmitted at fertilization to the conceptus, may be a major cause of embryonic mortality. The in vitro fertilization and embryo transfer (IVF/ET) procedure provides extra material--oocytes, zygotes, and embryos--to investigate the contribution of chromosomal abnormality to implantation failure. This paper reviews the results of cytogenetic studies on such material. Estimates from a total of 1120 oocytes from 11 studies give an overall proportion of chromosomal abnormality of 35%. Single and multiple nullisomies and disomies are found, involving nonrandom chromosome gain or loss. Hypohaploid complements are more frequent than hyperhaploid complements. The higher rate of chromosome loss of hypohaploid karyotypes was found to be largely artifactual. The estimated overall frequency of aneuploidy is 13%. In embryos the level of chromosomal abnormality is 23%-40%. Errors of fertilization are responsible for a substantial number of triploid embryos, many of which develop into mosaics. Factors extrinsic to the conceptus, such as infertility, advanced maternal age, and ovarian hyperstimulation, may increase the level of chromosomal abnormality. More refined methods for accurately recognizing and selecting chromosomally normal embryos for transfer are needed to improve the success rate of this reproductive technology.

Adult↗
PubMed1992

Failure of ritodrine to prevent preterm labor in the sheep.

OBJECTIVES: The purpose of this study was to determine whether continuous infusion of ritodrine could prevent preterm delivery in sheep. STUDY DESIGN: Sheep in preterm labor induced by RU 486 (mifepristone) received infusions of either ritodrine (n = 5) or saline solution (n = 5), and the progress of labor was monitored. beta 2-Adrenergic receptor density and function (agonist-induced cyclic adenosine monophosphate production) was measured in myometrial samples from both groups. RESULTS: Ritodrine initially inhibited labor contractions. This inhibition was only maintained for 16 hours, after which both the amplitude and frequency of electromyographic bursts and contractions returned. The failure of the myometrium to respond to ritodrine (desensitization) was associated with significant reductions in agonist-induced cyclic adenosine monophosphate production and beta 2-adrenergic receptor concentration in myometrial tissue collected from these animals compared with the saline solution-treated controls. CONCLUSIONS: Continuous infusion of ritodrine to sheep in preterm labor produces only a transient inhibition of contractions. This desensitization is caused by a down-regulation of myometrial beta 2-adrenergic receptors.

Animals↗
PubMed1992

Evidence for maternal predisposition to chromosome aneuploidy in multiple oocytes of some in vitro fertilization patients.

OBJECTIVES: To assess the rate of chromosome aneuploidy (e.g., extra or missing chromosomes) in oocytes remaining unfertilized in our in vitro fertilization (IVF) program. To determine whether two parameters of the IVF technique, advanced maternal age and hormonal follicle stimulation, affect this rate. DESIGN: Data on oocyte retrieval, fertilization, and aneuploidy rates are analyzed to test for possible relations with maternal age and two hormonal stimulation regimens. SETTING: Patients of our IVF program from 119 stimulated cycles over 8 months. PATIENTS, PARTICIPANTS: In vitro fertilization patients selected for having oocytes (1 to 18) remaining unfertilized after insemination in vitro. RESULTS: Advanced maternal age decreases both the number of retrieved oocytes and the fertilization rate, but hormonal treatments have no effect. Aneuploidy (rate 27%), involving group G most frequently, appears associated with advanced age. Patients who were previously parous produced significantly reduced numbers of aneuploid oocytes compared with the nonparous group. A significant excess (P = 0.01) of patients had multiple oocytes all alike (all haploid or all aneuploid), showing correlation among multiple oocytes of a patient in chromosome status. CONCLUSIONS: Maternal age affects reproductive performance and is related to specific chromosomal aneuploidy. Women who were previously parous are more likely to produce normal oocytes than nonparous women; oocyte normality therefore may improve the chance for a future successive pregnancy. Nonrandomness in chromosome abnormality of some patients' multiple oocytes is evidence for maternal predisposition to meiotic nondisjunction. Consequently, these patients are at risk for failed IVF cycles.

Adult↗
PubMed1992

Progesterone supplementation increases luteal phase endometrial thickness and oestradiol levels in in-vitro fertilization.

Luteal phase supplementation with natural progesterone appears to increase the pregnancy rate in in-vitro fertilization (IVF). The objective of this investigation was to examine the effect of intravaginal progesterone on endometrial thickness and hormonal parameters 7-9 days after embryo transfer. IVF patients receiving progesterone supplementation (Prog +, n = 64), who did not conceive, were compared to patients not receiving progesterone (Prog -, n = 23) because of failed fertilization. These two groups were also compared to 20 women (Preg) who conceived and to 16 women (control) in the mid-luteal phase of natural cycles. Endometrial thickness was greater (P < 0.01) in the Prog + (0.88 +/- 0.04 cm) and Preg (0.92 +/- 0.02 cm) groups compared to the Prog - (0.71 +/- 0.05 cm) and control (0.65 +/- 0.05 cm) groups. Mean luteal phase serum oestradiol levels were also higher (P < 0.05) in the Prog + (1118 +/- 112 pmol/l) and Preg (2267 +/- 757 pmol/l) groups than in the Prog - (574 +/- 70 pmol/l) and control (468 +/- 38 pmol/l) groups. These findings suggest that progesterone supplementation may affect pregnancy rates in IVF by increasing endometrial thickness, thereby enhancing receptivity for implantation. The mechanism through which this effect occurs is unclear but may involve serum oestradiol elevation.

Administration, Intravaginal↗
PubMed1992

Gonadotropin-releasing hormone agonist versus human chorionic gonadotropin for triggering follicular maturation in in vitro fertilization.

OBJECTIVE: To compare the use of gonadotropin-releasing hormone agonist (GnRH-a) with human chorionic gonadotropin (hCG) for triggering the final stage of follicular maturation for in vitro fertilization (IVF). DESIGN: In vitro fertilization outcome was determined in a randomized, prospective study. SETTING: The University of Toronto IVF program at The Toronto Hospital, Toronto General Division. PATIENTS AND INTERVENTIONS: One hundred seventy-nine women in the IVF program were given a subcutaneous injection of leuprolide acetate (500 micrograms) or an intramuscular injection of hCG (5,000 IU) 34 to 36 hours before oocyte retrieval. Vaginal progesterone (P) suppositories (50 mg) were used two times a day for luteal phase support. A subgroup of 41 women had serum estradiol (E2) and P levels determined 2 and 7 days after embryo transfer (ET). MAIN OUTCOME MEASURES: Pregnancy rates and luteal phase E2 and P were compared. RESULTS: In the GnRH-a group, there were 18 pregnancies from 84 ETs (20%). In the hCG group, there were 19 pregnancies from 95 ETs (19%). Luteal phase E2 and P levels were significantly lower in the GnRH-a group compared with the hCG group, and 18% of the former group had an apparent short luteal phase. CONCLUSIONS: Gonadotropin-releasing hormone agonist appears to be an effective alternative to hCG for inducing follicular maturation in IVF. The lower luteal phase E2 concentrations may potentially be beneficial in preventing ovarian hyperstimulation and for enhancing implantation. Better luteal phase support or a different dose of GnRH-a is needed to prevent luteal phase deficiency.

Chorionic Gonadotropin↗
PubMed1991

Clinical uses of gonadotropin-releasing hormone analogues.

Gonadotropin-releasing hormone (Gn-RH) analogues are synthetic derivatives of the native hypothalamic peptide with alterations in their chemical structure that result in changes in biologic activity. Several Gn-RH agonists are available for clinical use, and all act through the same mechanism: first to stimulate and then to inhibit gonadotropin and gonadal steroid secretion by downregulating the pituitary Gn-RN receptors. This review should provide clinicians with a working knowledge of the physiologic and pharmacokinetic features of Gn-RH agonists. Although over 2000 articles concerning Gn-RH analogues have been published I chose to review only those that were the first to report a novel clinical application. Gn-RH agonists have proved to be extremely efficacious in treating gonadal steroid-dependent problems such as endometriosis, uterine leiomyoma, precocious puberty and prostate and breast cancers, and they have resulted in very few side effects. Long-term use may, however, lead to skeletal calcium loss in women as a consequence of hypoestrogenism. Further research is needed to prevent this and maintain clinical efficacy.

Female↗
PubMed1991

A morphologic study of unfertilized oocytes and abnormal embryos in human in vitro fertilization.

The morphology of human, unfertilized oocytes and abnormal embryos cultured in vitro for 48-72 hr was examined in an attempt to learn more about oocyte maturation and reproductive failure in in vitro fertilization (IVF). About 21% of the unfertilized oocytes were totally degenerated. The majority (56%) of the remaining oocytes was arrested at the metaphase II stage. They contained coherent chromosomal plates and had extruded the first polar body with nuclear material. About 13% of oocytes underwent spontaneous activation. In most of these cases the second polar body was retained and many subnuclei or one big nucleus was formed. Five percent of metaphase II oocytes penetrated by sperm were not activated, likely as a result of oocyte immaturity. The developmental ability of abnormal embryos was poor. Several one-cell-stage zygotes were arrested at the pronuclear stage or at mitosis of the first mitotic division. Polyspermic embryos, especially those which contained four or more pronuclei, did not divide or formed uneven, multinucleated blastomeres. However, some triploid and tetraploid embryos often appeared normal morphologically despite their lethal chromosomal abnormalities.

Adult↗
PubMed1991

The effect of cryopreservation on the development of S- and G2-phase mouse embryos.

The survival rate and development of four-cell-stage mouse embryos frozen and thawed in S phase versus G2 phase was compared. Significantly more G2-phase than S-phase embryos survived freezing and thawing. In both groups, disruption of the zona pellucida, fusion of blastomeres, and dispersion of chromosomes were occasionally observed after thawing. Cryopreservation resulted in a longer delay in cleavage from the four- to the eight-cell stage of S (about 5 hr)- and G2-phase embryos (about 3 hr) compared to unfrozen controls. The number of frozen embryos which developed to the blastocyst stage was reduced compared to controls, and in the case of S-phase embryos, formation of the blastocyst cavity was also delayed. However, the average number of cells in the experimental and control embryos was similar. No increased incidence of chromosome abnormalities was seen. Our results suggest that freezing embryos in G2 is superior to freezing in S phase.

Animals↗
PubMed1991

Effect of follicular aspiration on hormonal parameters in patients undergoing ovarian stimulation.

The effect of follicular aspiration and oocyte retrieval on hormonal parameters was examined in women undergoing ovarian stimulation for in-vitro fertilization (IVF) compared to induced ovulation in women undergoing ovarian stimulation for intrauterine insemination (IUI). Blood samples were collected immediately before and 1 h after oocyte retrieval and 48 h later on the day of embryo transfer in 25 IVF patients and before the insemination and 48 h later in 20 IUI patients. A highly significant fall in serum levels of oestradiol (E2), progesterone (P) and human chorionic gonadotrophin (HCG), (P less than 0.001) was observed in the IVF group 1 h after follicular aspiration. The decline in serum E2 levels was maintained at 48 h. In contrast, there was no significant change in serum E2 levels in the IUI group during 48 h. The immediate decline in E2 levels after follicular aspiration might play a role in preventing ovarian hyperstimulation syndrome.

Chorionic Gonadotropin↗
PubMed1991

Multiple follicular recruitment and intrauterine insemination outcomes compared by age and diagnosis.

We studied the outcome of our intrauterine insemination (IUI) programme, evaluating female age and diagnosis. One-hundred-and-twenty-six patients less than 36 years of age (mean 30.91 +/- 3.02 years) completed 306 cycles of multiple follicular recruitment (MFR) and timed IUI; 64 patients greater than or equal to 36 years of age (mean 38.36 +/- 2.08 years) completed 166 cycles (total 190 patients, 472 cycles). The male partners' semen was prepared for IUI with wash and swim-up techniques. Diagnostic groups were: male factor (n = 26), idiopathic (n = 33), endometriosis (n = 19), ovulatory disorder (n = 7), other (n = 19) and combined factors (n = 86). Pregnancy rates (% per couple, % per cycle) [overall (31.58, 12.7)] [less than 36 years (38.10, 15.69)] [greater than 36 years (18.75, 7.23)] were greater in the less than 36 years group (P less than 0.025). The probability of conception after three treatment cycles was 0.402 overall, 0.481 for age less than 36 years and 0.252 for age greater than or equal to 36 years. The probability of conception for male factor and idiopathic infertility patients was 0.469 and 0.411 respectively. An age effect was found on pregnancy rates in the idiopathic group only. In conclusion, MFR + IUI is a valuable treatment especially for male factor patients and patients less than 36 years old, with idiopathic infertility.

Adult↗
PubMed1991

Evaluation and therapy of breakthrough bleeding in women using a triphasic oral contraceptive.

This study was designed to investigate the incidence and pattern of breakthrough bleeding (BTB) in 1,259 women who were prescribed for the first time a triphasic oral contraceptive (OC, 7-7-7) and to evaluate a hypothesis of management for BTB persisting after three cycles. The new users were compared with a control group of 696 women who had used various OCs for at least 6 months. The incidence of BTB in the control group was 16.8% and in the new users was 24.9%, 17.5%, and 15.3% in the first 3 months, respectively. Breakthrough bleeding occurred late in the 7-7-7 package in 58% and early or midway through the package in 17% and 25%, respectively. We hypothesized that late-package BTB would improve if the patient was switched to a monophasic pill similar to the relatively estrogenic formulation of the beginning of the package and vice versa for early or midpackage BTB. Seventy women with BTB at 3 months were randomly given 0.5/35 or 1/35 for a further 3 months. Breakthrough bleeding was more likely (P less than 0.05) to improve in women switched to 1/35 compared with 0.5/35 regardless of where in the package BTB occurred.

Adolescent↗
PubMed1990

Transvaginal ultrasonically guided follicular aspiration: a comparative study with laparoscopically guided follicular aspiration.

This study, comparing transvaginal ultrasound-guided follicle aspiration with laparoscopic-guided follicle aspiration for in vitro fertilization confirms that the use of laparoscopy appears to have no advantage for oocyte recovery over the ultrasonically directed technique. The latter offers potential benefits of less trauma, less risk, less morbidity, avoidance of general anesthesia, decreased operating room and personnel time, decreased expense, and in general, greater acceptance.

Adult↗
PubMed1990

Prediction of implantation by the sonographic appearance of the endometrium during controlled ovarian stimulation for in vitro fertilization (IVF)

The texture and the thickness of the endometrium as assessed by transvaginal sonography were prospectively evaluated in 123 patients undergoing IVF treatment. Three different types of endometrial patterns could be distinguished: (A) an entirely homogenous, hyperechogenic endometrium; (B) an intermediate type characterized by the same reflectivity of ultrasound as the myometrium, with a nonprominent or absent central echogenic line; and (C) a multilayered endometrium consisting of prominent outer and midline hyperechogenic lines and inner hypoechogenic regions. On the day before oocyte retrieval, endometrial thickness was significantly greater in the group of patients who achieved pregnancy than in the group who did not (8.7 +/- 0.4 vs 7.5 +/- 0.2 mm, respectively; P less than 0.01) and significantly more patients had multilayered, pattern C, endometrium (75% in pregnant women vs 42.4% in nonpregnant women; P less than 0.01). No pregnancy occurred when the endometrial thickness was less than 6 mm. When type C endometrium greater than or equal to 6 mm thick was seen, the pregnancy rate per embryo transfer was 39%. When type A or B endometrial pattern was seen, the negative predictive value for the occurrence of pregnancy was 90.5%. Our results suggest that transvaginal sonographic evaluation of endometrial texture and thickness may be an indicator of the likelihood of achieving pregnancy.

Adult↗
PubMed1990

The effect of hysterectomy and bilateral oophorectomy in women with severe premenstrual syndrome.

The etiology of premenstrual syndrome is unknown, although this syndrome is linked to the menstrual cycle. Fourteen women with severe, debilitating premenstrual syndrome volunteered for a study of therapy by hysterectomy, oophorectomy, and continuous estrogen replacement. All had completed their families and had failed to benefit from previous medical treatment. The diagnosis and severity of premenstrual syndrome were assessed by means of prospective charting and psychological evaluation. All patients had clearly cyclic symptoms and psychological scores consistent with a major disruption of their lives before surgery. Six months after surgery, premenstrual syndrome symptom charting revealed complete disappearance of a cyclic pattern with scores equivalent to those of a normal population. Psychological measures 6 months after operation showed dramatic improvement in mood, general affect, well-being, life satisfaction, and overall quality of life. Surgical therapy, involving oophorectomy, hysterectomy, and continuous estrogen replacement, is effective in relieving the symptoms of premenstrual syndrome and is indicated for a small, selected group of women.

Adult↗
PubMed1990

Gonadotropin suppression with oral contraceptives before in vitro fertilization.

One hundred eighty-one stimulation cycles in which gonadotropin suppression with oral contraceptives (OCs) preceded induction of follicle stimulation (study group) and 113 stimulation cycles without pituitary suppression (control group) were compared. The mean length of ovarian suppression was 35.3 +/- 0.9 days. No spontaneous luteinizing hormone (LH) surges occurred when the use of OC preceded ovarian hyperstimulation, whereas in the control group the incidence of LH surges was 19.5%. The mean amount of human menopausal gonadotropin required was significantly lower in the study group than in the control group (8.9 +/- 0.4 and 10.9 +/- 0.4 ampules, respectively). Significantly more follicles greater than or equal to 1.5 cm in diameter were seen on the day before oocyte retrieval and significantly more oocytes were retrieved per attempt in the group with OC pretreatment. Our data clearly demonstrate that OCs are useful in vitro fertilization stimulation protocols to facilitate scheduling of cycles and to prevent spontaneous LH surges.

Abortion, Spontaneous↗
PubMed1990

Transient hyperprolactinemia is associated with a midcycle luteinizing hormone surge.

This study demonstrates that LH surge cycles in IVF patients were associated with significantly higher serum PRL concentrations than cycles in which a spontaneous LH surge did not occur. Our findings support the hypothesis of concomitant LH and PRL release at the time of the midcycle gonadotropin surge, as well as that of estrogen sensitization of pituitary lactotropes, and suggest a possible mechanism for transient midcycle hyperprolactinemia.

Chorionic Gonadotropin↗