Multiple pregnancies: action is taking place.
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Adult↗
Biomedical subjects
M R Soules
Publications and source records attributed to M R Soules.
The future of human ovarian cryopreservation and transplantation: fertility and beyond.
OBJECTIVE: To review the current progress in ovarian cryopreservation and transplantation and to discuss the obstacles with the clinical application of this technique. DESIGN: The literature on ovarian cryopreservation and transplantation was reviewed to facilitate understanding and predict future directions. The studies related to this topic were identified through MEDLINE and other bibliographic databases, focusing on the most recent developments. CONCLUSION(S): The experimental evidence for low-temperature storage of ovarian tissue is encouraging. Although restoration of fertility with cryopreserved ovarian grafts has been successful in various animals, there are uncertainties about the optimum use of stored ovarian tissue in humans. Autotransplantation appears to be promising, but the potential risk of transmitting malignant cells in women with cancer is of great concern. The maturation of primordial follicles with xenotransplantation is encouraging, but the efficacy and the safety of this method need further investigation. Furthermore, the quality of oocytes that have been matured in a host animal is unknown. The development of in vitro culture systems for oocyte maturation is still in its infancy. There are many issues to be resolved in ovarian transplantation before the full clinical use of this emerging technique. Most of all, there is an urgent need to optimize the freeze/thaw procedure and to find the means to protect grafts from ischemia-reperfusion injury. Nevertheless, ovarian transplantation should prove to be clinically useful for women at risk for premature ovarian failure.
Cellular Senescence↗
Human reproductive cloning: not ready for prime time.
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Cloning, Organism↗
Executive summary: Stages of Reproductive Aging Workshop (STRAW).
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Aging↗
Stages of Reproductive Aging Workshop (STRAW).
A select group of clinicians and investigators met recently for the express purpose of developing a staging system for female reproductive aging. The group also addressed the confusing and redundant nomenclature that is commonly used to describe the late reproductive years. A summary and recommendations are presented.
Aging↗
Executive summary: Stages of Reproductive Aging Workshop (STRAW).
A select group of investigators attended a structured workshop, the Stages of Reproductive Aging Workshop (STRAW), at Park City, Utah, USA, in July 2001, which addressed the need in women for a staging system as well as the confusing nomenclature for the reproductive years.
Aging↗
Bacteria in the transfer catheter tip influence the live-birth rate after in vitro fertilization.
OBJECTIVE: To assess the impact of individual bacteria isolated from the vagina and tip of the embryo transfer catheter on live-birth rates. DESIGN: Prospective clinical study. SETTING: Infertility outpatient clinic of a university hospital. PATIENT(S): Ninety-one women undergoing IVF-ET. INTERVENTION(S): Cultures were obtained from the vagina for aerobic and anaerobic bacteria at the time of both sonographic egg retrieval and embryo transfer and from the tip of the embryo transfer catheter. Doxycycline treatment was started after egg retrieval. MAIN OUTCOME MEASURE(S): The live birth of one or more neonates. RESULT(S): Doxycycline had no substantial impact on the recovery of individual vaginal bacteria or on bacterial vaginosis. An increase in live-birth rate was associated with the recovery of hydrogen peroxide-producing Lactobacillus from the vagina (P=0.01) and from the embryo transfer catheter (P=0.01). In contrast, a reduction in live-birth rate was associated with recovery of Streptococcus viridans (S. viridans) from the embryo transfer catheter tip (P=0.04). CONCLUSION(S): In the setting of IVF-ET, prophylactic doxycycline had little effect on vaginal bacteria. Specific bacteria recovered from the embryo transfer catheter appear associated with a detrimental or beneficial effect or with no effect on live-birth rates.
Adult↗
Ovarian follicular concentrations of activin, follistatin, inhibin, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-2 (IGFBP-2), IGFBP-3, and vascular endothelial growth factor in spontaneous menstrual cycles of normal women of advanced reproductive age.
Previous studies indicate that the menstrual cycles of older reproductive age women are characterized by a selective elevation of FSH associated with early development and ovulation of a dominant follicle. Several intraovarian hormones and growth factors have been identified that appear to serve important paracrine roles. The purpose of this study was to examine follicular fluid (FF) hormones and growth factors in the dominant follicle of unstimulated cycles of older, ovulatory women. We aspirated FF from the preovulatory dominant follicle in natural menstrual cycles of older subjects (age, 40-45 yr; n = 20) and younger controls (age, 20-25 yr; n = 19). FF was analyzed for estradiol, progesterone, testosterone, androstenedione, inhibin A and B, total activin A, total follistatin, insulin-like growth factor I (IGF-I), IGF-II, IGF-binding protein-2 (IGFBP-2), IGFBP-3, and vascular endothelial growth factor (VEGF) concentrations. We found that the dominant follicles from older women contain normal concentrations of steroids, inhibin A and B, IGF-II, IGFBP-2, and IGFBP-3; increased concentrations of follistatin, activin A, and VEGF; and decreased concentrations of IGF-I. Therefore, under the influence of elevated FSH, the dominant follicle in older women is highly competent in terms of hormone and growth factor secretion. We postulate that elevated FF activin may be related to the early ovulation observed in older women, whereas elevated VEGF may be related to the meiotic spindle abnormalities observed in the oocytes of older reproductive age women.
Activins↗
The pattern of infertility diagnoses in women of advanced reproductive age.
OBJECTIVE: Our intention was to determine whether there is a unique pattern of infertility diagnoses in older infertile couples. STUDY DESIGN: The design of this study was a retrospective chart review study. It was performed in a tertiary referral reproductive medicine unit. There were 2 groups of patients-couples: group 1, female partner aged 20-29 (n = 105) at presentation; group 2, female partner aged 40-45 (n = 112) at presentation. All women underwent infertility evaluations between 1989 and 1994. There were no interventions. The prevalence of standard infertility diagnoses was the main outcome measure. RESULTS: The prevalence of 8 major infertility diagnoses in the younger and older groups (each couple could have >/=1 diagnosis) was as follows: (1) ovulatory factor-younger group, 56%; older group, 30%; (2) tubal factor-younger group, 34%; older group, 29%; (3) endometriosis-younger group, 13%; older group, 17%; (4) uterine factor-younger group, 1%; older group, 5%; (5) cervical factor-younger group, 4%; older group, 1%; (6) luteal deficiency-younger group, 4%; older group, 10%; (7) male factor-younger group, 32%; older group, 45%; (8) unexplained-younger group, 5%; older group, 10%. The only significant difference was an increase in ovulatory factor in the younger group. CONCLUSIONS: There is no unique pattern of infertility diagnoses in women of advanced reproductive age as seen at a tertiary referral center. We speculate that a high false-positive rate associated with standard infertility tests and a different referral pattern for older couples obscures any real differences in the etiology of infertility in older couples.
Adult↗
Inhibin-B as a test of ovarian reserve for infertile women.
The objective of the study was to compare a standard clomiphene citrate challenge test with inhibin-B serum concentrations also obtained on cycle days 3 and 10 as a negative predictor of pregnancy in a group of 106 women at risk for compromised ovarian function. Mean duration of follow-up was 8.25 months in 95 patients with 30 pregnancies recorded (plus one biochemical). Inhibin-B concentrations on cycle days 3 and 10 were correlated only with each other and not with serum oestradiol, follicle stimulating hormone (FSH) and/or pregnancy rates. Pregnancy occurred in 34.5% (10/29) of all patients with inhibin-B values >/=45 pg/ml on cycle day 3 and in 31.8% (21/66) of those with values <45 pg/ml. For FSH >11 mIU/ml on either day, pregnancy rate was 13.6% versus 38.4% for FSH of </=9 mIU/ml (P = 0.03). This study reconfirmed the usefulness of a clomiphene citrate challenge test as an indication of ovarian reserve but failed to find clinical value for inhibin-B testing.
Adult↗
Morphometric analysis of primordial follicle number in pigtailed monkey ovaries: symmetry and relationship with age.
We previously described a modern, three-dimensional counting method for determining primordial follicle (PF) numbers in primate ovaries using a combination of fractionator and physical dissector techniques. The purposes of our current study were 1) to apply our method to describe intraindividual differences in PF numbers between ovaries and 2) perform a linear regression analysis of age versus mean PF number per ovary. Ovaries from 16 pigtailed monkeys (Macaca nemestrina) age 0.85-12.5 yr were examined. Both ovaries were available from 11 subjects. The difference between ovaries ranged from 2% to 22% (mean +/- SD, 10 +/- 7%) and was not statistically significant. Regression analysis of data from all 16 subjects displayed a log-linear relationship according to the equation log N(a) = 4.8542 - 0.0714(age) where N(a) is the number of PF at a given chronological age. The fit for this model was highly significant (r(2) = 0.73, p </= 0.0001). Extrapolation of the model suggests that there are 71 483 PF in each ovary at the time of birth. We conclude that right and left ovaries differ little and that PF numbers follow a log-linear rate of decline during the reproductive years in this species.
Aging↗
Commentary: posthumous harvesting of gametes--a physician's perspective.
Author offers a clinical perspective on problems arising from requests for postmortem sperm and oocyte retrieval.
Brain Death↗
Inhibin and reproductive aging in women.
The monotropic FSH rise is the sentinel endocrine event that first indicates a woman is approaching the end of her reproductive potential. While a deficiency in inhibin has long been postulated as the immediate cause of the monotropic FSH rise, this has only recently been demonstrated to actually occur. It is our current hypothesis that when the number of preantral follicles in both ovaries drop below a threshold, then there is a subtle decrease in inhibin B which leads to the monotropic FSH rise which, in turn, accelerates follicular depletion and the attainment of the menopause.
Aging↗
Endocrine changes of the perimenopause.
Reproductive aging in women is closely tied to the loss of ovarian follicles through atresia. The sentinel endocrinologic finding is the monotropic FSH rise, associated with a decline in ovarian inhibin B secretion. Fertility becomes significantly compromised long before overt clinical signs occur, such as cycle irregularity. Compromised fertility is primarily related to oocyte dysfunction. As women with regular cycles near the end of the reproductive years, the following changes are usually manifested: 1) the selection and development of a dominant follicle occurs earlier; 2) there is earlier ovulation; 3) there is a short follicular phase and total cycle length; and 4) ovarian steroid secretion is normal. The relationships, if any, between the monotropic FSH rise, accelerated follicular atresia, shortened follicular phase, and oocyte quality remain to be determined. The next phase of reproductive aging is the perimenopause. Lack of predictability is the rule with regard to the nature and duration of the perimenopause. Long cycles are interspersed with short ones, and intermittent ovulatory cycles are intermingled with periods that are hormonally indistinct from the postmenopausal state. Even after the last menstrual period, evidence of intermittent ovarian estradiol production may still be detected. Although fertility is severely compromised during the perimenopause, ovulation may occur without warning and contraception must be practiced if pregnancy is not desired. Further studies are needed to elucidate the factors contributing to oocyte abnormalities in women of advanced reproductive age, as well as the factors that determine the rate of follicle atresia and the length of the reproductive life span.
Aging↗
Serum inhibin and disease status in women with ovarian granulosa cell tumors.
OBJECTIVE: To determine if immunoreactive inhibin assayed in serum from women with granulosa cell tumors correlated with tumor burden, reflected response to treatment, or predicted recurrent disease. STUDY DESIGN: Serum samples were collected following bilateral oophorectomy (BSO) with or without other indicated surgery in 15 patients with granulosa cell tumors. Inhibin radioimmunoassay (RIA-Inh) was performed on all samples and results were correlated with tumor burden, disease status, and treatment response. RESULTS: Fifteen patients had serum assayed for inhibin with levels ranging from 0 to 7470 U/liter. In 4 patients with measurable recurrent disease, inhibin levels correlated directly with tumor burden (r2 = 0.96). Four patients had serum drawn during clinical remission and in all 4 patients elevated inhibin levels predated recurrence by a median interval of 11.5 months (range 7-20). The remaining 7 were treated for primary disease and were in clinical remission with a median follow-up of 33 months (range 9-53). Four of these 7 patients were surgically staged: 2 were FIGO Stage I and inhibin levels fell to 0 U/liter; 2 patients had metastatic disease (Stage IIc and IIIa) and their inhibin levels were found to be elevated following complete resection. The remaining 3 were not surgically staged, and all had elevated inhibin levels while in clinical remission, suggesting occult disease. Of the 15 total patients, 1 who was treated with chemotherapy for recurrent disease was followed with serial inhibin levels. She showed a complete response to therapy with inhibin levels falling from 975 to 0 U/liter with 15 months follow-up. CONCLUSIONS: Serum inhibin levels reflect tumor burden and may be valuable in assessing response to chemotherapy or predicting recurrent disease in women with granulosa cell tumors who have had BSO. Serum inhibin level evaluation should be incorporated into large-group trials of therapy for granulosa cell tumors.
Female↗
Congenital cervical atresia: report of seven cases and review of the literature.
OBJECTIVE: Our aim was to evaluate the clinical course and management of congenital cervical atresia. STUDY DESIGN: This retrospective analysis included 7 patients referred to our clinic and a review of the medical literature. RESULTS: Including this case series, 58 cases of congenital cervical atresia have been reported in the literature. Forty-eight percent of patients had isolated congenital cervical atresia with a normal vagina whereas the remainder had either complete or partial vaginal atresia ("shortened blind vaginal pouches"). Surgical management has included abdominal hysterectomy or uterovaginal cannulation with or without vaginoplasty. In 59% of patients who underwent uterovaginal canalization procedures (23/39), normal menstrual bleeding was achieved. Four of these patients subsequently became pregnant and were delivered at term. CONCLUSION: Surgical canalization in selected patients with congenital cervical atresia can be successfully performed to provide patients an opportunity for conservative management, resulting in normal menstrual bleeding, resolution of cyclic pelvic pain, and some potential (albeit limited) for fertility.
Abnormalities, Multiple↗
Correlation of reproductive aging with function in selected organ systems.
OBJECTIVE: To compare day 3 FSH levels with biomarkers of aging in other organ systems in healthy, older, reproductive age women. DESIGN: Cross-sectional pilot study. SETTING: Healthy volunteers in an academic, tertiary care center. PATIENT(S): Healthy, regularly cycling women aged 40 to 45 years divided into two groups: those with normal day 3 FSH levels and those with elevated day 3 FSH levels. INTERVENTION(S): Blood and urine collection with blood pressure measurement, pulmonary function testing, bone densitometry, and skin biopsy. MAIN OUTCOME MEASURE(S): Comparison between groups for serum creatinine, albumin, glucose, hematocrit, DHEAS, fasting insulin, low-density lipoprotein cholesterol, and triglyceride levels; creatinine clearance (CrCl); forced expiratory volume in 1 second; forced vital capacity; bone density at the wrist, hip, and lumbar spine; and mean dermal thickness. RESULT(S): Hematocrit and CrCl values were significantly lower in the group with high FSH levels. Creatinine clearance also was significantly negatively correlated with FSH level. After Bonferroni adjustment for multiple testing, all measures were no longer different at the P < or = 0.05 level. CONCLUSION(S): Aging of the hypothalamic-pituitary-ovarian axis may parallel aging in other organ systems. Further longitudinal analyses are necessary to ascertain whether these measures will predict reproductive reserve before irreversible dysfunction occurs.
Adult↗
Function and structure of cilia in the fallopian tube of an infertile woman with Kartagener's syndrome.
In Kartagener's syndrome (KS), primary defects of the ciliary axoneme cause dyskinetic ciliary motion. Because ciliary motion is an important factor in normal ovum transport, ciliary dyskinesia may cause infertility. On the other hand, the existence of some ciliary activity, albeit abnormal, may account for fertility in some women with KS. In this case study, an infertile woman diagnosed with KS had normal results in all usual infertility tests. Biopsies of tubal mucosa were obtained at laparoscopy for ovum recovery during an in-vitro fertilization cycle. Ciliary activity, measured by laser light-scattering spectroscopy, was detected in all tubal specimens; however the majority of regions sampled showed no activity. In active regions, beat frequency ranged from 5 to 10 Hz, approximately 30% of normal. Electron microscopy showed similar morphological defects in both tubal and nasal mucosa. The number of cilia per cell was approximately 20% of normal. The major ultrastructural abnormality of cilia was an absence of the central microtubules. The only demonstrable explanation for this patient's infertility was primary ciliary dyskinesia associated with KS.
Adult↗