Shared oocyte donation: society's benefits.

OBJECTIVE: To assess the efficacy of oocyte donation when a cohort of oocytes is shared between two phenotypically matched recipients. DESIGN: A retrospective analysis of a program using shared anonymous oocyte donation. SETTING: Academic infertility center. PATIENT(S): Recipient women with partial or complete ovarian failure; oocyte donors who have been properly screened. INTERVENTION(S): Each oocyte donor was phenotypically matched with two potential recipients. The cohort of donated oocytes were divided between these two recipients if eight or more mature oocytes were obtained at retrieval. Recipients underwent hormone replacement therapy consisting of down-regulation with a GnRH agonist, transdermal estradiol, and intramuscular progesterone in a dose determined by a previous preparatory cycle. MAIN OUTCOME MEASURE(S): Pregnancy and delivery rates for all transfers originating from a cohort of oocytes obtained by retrieval of a single donor; pregnancy and delivery rates per recipient; rate of conversion of a shared donation cycle to a single recipient. RESULT(S): A total of 249 donor cycles permitted 241 retrievals. Each recipient received 8.3 +/- 3.5 oocytes per donation. There were 424 fresh ETs and 48 frozen ETs performed. For fresh ETs, clinical pregnancy and ongoing or delivery rates per recipient were 56.8% and 49.7%, respectively. For frozen ETs, these rates were 50% and 39.5%. Implantation rates were 31.8% and 26.1% for fresh and frozen ET, respectively. When analyzed per donor retrieval, clinical pregnancy and ongoing or delivery rates were 109.5% and 95.4%. These high pregnancy rates per donor reflect the numerous fresh and frozen ETs that can result from one donor's retrieval. Conversion of a donation cycle from two recipients to one recipient occurred for 26 of 241 cycles (10.8%). CONCLUSION(S): Shared anonymous oocyte donation provides a very high pregnancy rate per donor retrieval that is not achievable with unshared donation. In addition, there is a diminished risk exposure of donors per total completed recipient transfers. We support shared oocyte donation as the most efficient use of the precious resource of human oocytes.

Oocyte donation: insights into implantation.

OBJECTIVE: To ascertain whether obstetric, gynecologic, or congenital variables affect implantation efficiency or eventual delivery in donor oocyte recipients. DESIGN: Clinical study. SETTING: Academic tertiary care infertility clinic. PATIENT(S): A total of 370 recipients. INTERVENTION(S): Fresh ET following oocyte donation in a hormone replacement cycle. MAIN OUTCOME MEASURE(S): Regression analyses were performed to detect any statistically significant difference in the pregnancy rate (PR), delivery rate, miscarriage rate, or implantation rate associated with different obstetric, gynecologic, and congenital independent variables while accounting for the age of the recipient in each analysis. RESULT(S): For all recipients, a clinical PR per transfer of 58.9% was achieved, with an implantation rate of 30%. A significant decline in the implantation rate was noted in relation to increasing age of the recipient. A history of tubal disease was associated with a significantly lower implantation rate and a significantly lower ongoing and delivered PR. Asherman's syndrome, despite surgical correction, appeared to negatively affect the ongoing and delivered PR. CONCLUSION(S): With the exceptions of recipient age and a history of tubal disease, all other uterine factors studied did not appear to influence the implantation potential of an embryo resulting from oocyte donation. A history of tubal disease had a distinctly negative effect on implantation efficiency and delivery potential for a given recipient. This finding highlights the need to identify the mechanisms underlying the negative effect of tubal disease so that donor oocyte recipients and all other patients with this cause of infertility can benefit from directed therapy.

Oocyte donation: does a previous attempt affect a subsequent attempt?

OBJECTIVE: To analyze the effect of a previous donor oocyte cycle on the outcome of subsequent attempts. DESIGN: Retrospective study. SETTING: Oocyte donation program at The New York Hospital/Cornell Medical Center. PATIENT(S): Two hundred sixty-seven patients undergoing 354 fresh cycles of oocyte donation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Clinical outcomes were divided into groups based on the attempt number of each cycle for each patient. Results were calculated for each recipient cycle. RESULT(S): A clinical pregnancy rate of 56.2% and ongoing pregnancy/delivery rate per retrieval of 50.3% were noted. No statistically significant differences in clinical outcomes were found between the first, second, and third attempts. A significant increase was noted in the ongoing pregnancy/delivery rate per recipient cycle for the second attempt in those patients who had a delivery after the first attempt compared with those who did not. CONCLUSION(S): We demonstrated an overall clinical pregnancy rate of 56.2% and an ongoing pregnancy/delivery rate of 50.3% per retrieval. Outcome for the second attempt was associated with success or failure during an initial attempt at oocyte donation.

Families created through ovum donation: a preliminary investigation of obstetrical outcome and psychosocial adjustment.

PURPOSE: This study attempted to obtain preliminary follow-up information regarding obstetrical outcomes and the psychosocial well-being of families created through the ovum donation. There is presently very little known about this population with respect to obstetrical care, health status of offspring, family and marital relationships of recipient couples, or how couples feel about having chosen ovum donation as a family-building option. RESULTS: Fifty-nine couples were initially surveyed and, ultimately, extensive information was obtained for 30 husbands, 31 wives, and 51 offspring. There was a very high percentage of cesarean section deliveries (81.6%), and although a few children experienced health problems at birth, they are all now in good health and developmental milestones are within normal limits. Information was also obtained about breast-feeding experiences, choice of donor (known [sister] or anonymous), reasons for choosing ovum donation over other parenting options, and the impact of this choice on marital and family relationships. Demographic data were also obtained. CONCLUSIONS: For many infertile couples, the long struggle to become parents culminated in a successful birth, and the experience of pregnancy seemed to meet a need to be both biological and psychosocial parents. In general, subjects were extremely cooperative with the investigation and they indicated a desire to learn as much as possible about the psychosocial status of families created through ovum donation. As the assisted reproductive technologies move rapidly into the 21st century, it now seems imperative that health and mental health professionals gain more knowledge about the impact of third party reproduction and the psychosocial adjustment and well-being of families created by this medical technology.

The incidence of luteal phase defect in normal, fertile women, determined by serial endometrial biopsies.

Five regularly menstruating women of proven fertility, with normal prolactin and thyroid function studies, underwent a total of 39 endometrial biopsies (EMBs). The slides were dated in blinded fashion, and the cycle date determined by considering the date of the next menstrual period as day 28 and counting backward. Using a 2-day or greater lag in endometrial maturity to define a luteal phase defect (LPD), the incidence of single and sequential out-of-phase EMBs was 51.4% and 26.7%, respectively. Using a 3-day or greater lag to define a LPD, the incidence of single and sequential out-of-phase EMBs was 31.4% and 6.6%, respectively. These incidences in normal, fertile women are as high as the rates quoted for infertile populations, and call into question the standard criteria for defining this condition and evaluating therapies to correct it.

Sequential changes in plasma luteinizing hormone and plasma prorenin during the menstrual cycle.

Prorenin, the enzymatically inactive biosynthetic precursor of renin, is secreted by the kidneys. However, the ovaries appear to be the source of the cyclical increase in plasma prorenin that occurs in the middle of the menstrual cycle. In this study we examined the temporal relationship between changes in plasma prorenin and LH in normal women to determine whether ovarian prorenin secretion might be stimulated by LH. Blood was collected from nine normal women daily for 7 days in the midcycle period and from six of them every 8 h on 6 of these days. Time zero was taken as the highest plasma LH value. The initial rise in LH (-24 h) preceded the initial rise in prorenin (-8 h) and the LH peak preceded the prorenin peak by 8-16 h. These sequential increases in plasma LH and prorenin occurred in the presence of high plasma estradiol levels. While LH fell in parallel with estradiol, the prorenin peak was more sustained and plasma prorenin remained above baseline at 40 and 48 h, at a time when both estradiol and LH had reached a new basal level. These results suggest that gonadotropins stimulate ovarian prorenin release. The timing of the changes in plasma prorenin and its presence in high concentrations in ovarian follicular fluid suggest that prorenin may be involved in the process of ovulation. The results also suggest that changes in plasma prorenin may determine the activity of an ovarian renin system that functions independently of circulating active renin.

Oral contraceptives and dysmenorrhea.

PIP: This artical examines the risks and benefits associated with use of the oral contraceptive pill (OCP) by adolescents and the various alternatives and methods of prescribing OCPs. Any adolescent who is either sexually active or contemplating sexual activity should be offered a contraceptive method that is appropriate to her individual needs. The contraceptive needs to be highly effective, safe and within the means and desires of the adolescent. For the majority of teenagers, the contraceptive of choice will be the OCP. The IUD should almost never be prescribed to the adolescent. Most OCPs marketed today are combination pills containing both an estrogen and a progestin in each pill. A variety of contraceptive actions combines to create a contraceptive method that is 99.3-99.9% effective. OCPs provide some protection against the development of pelvic inflammatory disease (PID). Oral contraceptives also decrease the incidence of anemia by decreasing the amount and duration of menstrual flow. Ovarian cysts do not form in the ovaries of the OCP user. On the other hand, a serious risk of the use of OCPs is the increased danger of thromboembolic events including deep venous thrombosis, pulmonary embolus, and myocardial infarction. The increased risk of myocardial infarction in OCP users is additive with other risk factors including hypertension, hypercholesterolemia, cigarette smoking, obesity, diabetes mellitus, and age. OCP use seems to provide some protection against development of endometrial or ovarian cancer. Oral contraceptives are associated with the development of benign hepatocellular adenomas. A variety of metabolic and hormonal alterations also occur in pill users. Most appropriate for the adolescent is a formulation containing a low dose of estrogen because of the decreased risk of thromboembolic complications. Dysmenorrhea effects more than 1/2 of female adolescents, and can best be treated with ibuprofen.^ieng

Plasma prorenin during early pregnancy: ovarian secretion under gonadotropin control?

To explore the time-course and the source of the changes in plasma prorenin that occur in early pregnancy we studied a normal subject (subject 1), an in vitro fertilization (IVF) patient (subject 2) and an ovarian failure patient who received a donor egg (subject 3). Day 0 was the luteinizing hormone (LH) peak (subject 1), the day of human chorionic gonadotropin (hCG) administration (subject 2) or 3 days before embryo transfer (subject 3). In subjects 1 and 2 prorenin increased transiently (three- and ninefold respectively) on days 0-4, then returned towards baseline and began to increase again around day 12 to a maximum (six- and 26-fold baseline) around day 20. Active renin was consistently less than 10% of total renin. In the ovarian-failure patient only small fluctuations occurred in total renin yet her hCG was 137 mlU/ml on day 15, proving that she was pregnant. These results suggest that the prorenin rise that occurs at mid-menstrual cycle and following conception may be due to ovarian prorenin secretion in response to stimulation by gonadotropic hormones.

Observations in a preliminary open trial of estradiol therapy for senile dementia-Alzheimer's type.

Previous studies have suggested that estrogen may have an effect on cognitive and emotional function in women. Studies in rodents and non-human primates have demonstrated the presence of estrogen receptors in brain, and that estrogen can affect behavior in animals. Estrogen administration to ovariectomized rats increases choline acetyltransferase activity in certain regions of brain. Choline acetyltransferase activity is known to be significantly decreased in senile dementia-Alzheimer's type (SDAT). Based on these observations, we treated seven women with SDAT with low dosages of estradiol over a six week period. A battery of assessments was performed throughout the study period. Significant improvements in three women were noted on measures of attention, orientation, mood and social interaction. These estrogen-responsive women were characterized by dementia associated with an affective disorder, older age at onset, and evidence of osteoporosis. Side effects of estradiol therapy included withdrawal bleeding in one woman and transient breast tenderness in another. Estradiol therapy thus may benefit some postmenopausal women with SDAT. The occurrence of osteoporosis in the estrogen-responsive group suggests that SDAT in some women may be associated with or related to a systemic estrogen deficiency state. However, considering the potential for serious side effects as a result of estrogen therapy, the current risk to benefit ratio precludes the routine clinical use of estrogen for dementia until careful clinical research trials have been performed.

Prolactin response to breast stimulation in lactating women is not mediated by endogenous opioids.

Several reports have shown that the prolactin response to suckling in rats can be blunted by administration of the opiate antagonist naloxone. In order to investigate whether the prolactin response to breast stimulation in women is similarly affected by naloxone, nine healthy lactating women participated in 10 studies. Each woman served as her own control and was studied on two occasions, receiving pretreatment with either saline solution or naloxone. Prolactin was measured in the baseline state and for 60 minutes after the onset of a 20-minute period of nipple stimulation by use of the Egnell mechanical breast pump. Neither baseline nor stimulated prolactin values were different by paired t test. Thus, in contrast to rats, an opioid pathway does not appear to be involved in the prolactin response to suckling in humans.

The influence of hypermagnesemia on serum calcium and parathyroid hormone levels in human subjects.

We measured serum concentrations of calcium and parathyroid hormone in seven pregnant women who were receiving intravenous magnesium sulfate for the suppression of premature labor. After administration of magnesium sulfate, the mean (+/- S.E.M.) serum magnesium level rose rapidly from the normal base-line level of 2.0 +/- 0.2 mg per deciliter to 6.1 +/- 0.4 mg per deciliter (0.8 +/- 0.1 to 2.5 +/- 0.2 mmol per liter) (P less than 0.001) at 30 minutes and remained markedly elevated. Concentrations of total and ionized calcium fell gradually in all subjects from normal base-line concentrations, 8.6 +/- 0.2 and 4.4 +/- 0.1 mg per deciliter (2.2 +/- 0.1 and 1.1 +/- 0.03 mmol per liter), respectively, into the hypocalcemic range, reaching a nadir of 7.6 +/- 0.2 and 3.9 +/- 0.1 mg per deciliter (1.9 +/- 0.1 and 0.98 +/- 0.03 mmol per liter), respectively, at three hours (P less than 0.001). Parathyroid hormone levels fell rapidly in response to magnesium infusion, from 13.1 +/- 2.5 to 7.8 +/- 0.7 pg per milliliter at 30 minutes, and were significantly below base-line levels for two hours despite frank hypocalcemia. These results suggest that hypermagnesemia rapidly decreases the secretion of parathyroid hormone in vivo in human subjects and that parathyroid hormone levels remain depressed despite concomitant hypocalcemia. The results also suggest that the hypocalcemia associated with hypermagnesemia may be due in part to the suppressive effects of hypermagnesemia on parathyroid hormone secretion.

Structure and function of the fallopian tubes following exposure to diethylstilbestrol (DES) during gestation.

The association between the use of diethylstilbestrol (DES) and vaginal and cervical adenocarcinoma and adenosis in the progeny was first reported by Herbst et al. in 1971. This progeny will reach a peak as far as reproduction is concerned in this decade. It is estimated that 2 million women may be involved to varying degrees. Changes in uterine and cervical contour and structure have been detailed. Thus DES exposure and anatomic changes in the Müllerian system have been documented. In this report 16 women in the reproductive age group who were exposed to DES in utero and presented with infertility are discussed. On workup for infertility they were found to have unique tubal morphologic features consisting of a foreshortened, convoluted tube with "withered" fimbria with a pinpoint os at laparoscopy. The diagnosis could not be made at the time of hysterosalpingogram. Three patients had surgery in an attempt to correct this condition; and in all cases the surgery was unsuccessful. No statistical data is offered as to epidemiologic factors or incidence rates, but the suspected increase in infertility and ectopic pregnancy rates in patients with DES exposure may corroborate these findings.