The Role of Preparatory Cycles in Ovum Donation Recipients: A Retrospective Study

Purpose: To determine whether preparatory cycles affect in vitro fertilization (IVF) outcome in ovum donation.Methods: Medical records of 98 ovum donation recipients undergoing their first egg donation cycle were analyzed retrospectively. Preparatory cycles were performed in 50 patients with leuprolide acetate, estrogen, and progesterone. An endometrial biopsy was performed on day 10–12 of progesterone supplementation, to determine adequacy of the preparatory cycle.Results: Pregnancy rates in women with and without preparatory cycles were 42.0% and 43.8%, respectively. Among ovum donation recipients who underwent preparatory cycles, the percentages of adequate endometrial biopsies in pregnant versus nonpregnant groups were 76.2% and 84.3%, respectively. No results showed statistical significance.Conclusions: Preparatory cycles do not increase pregnancy rates in ovum donation recipients. In addition, no correlation was noted between adequate endometrial biopsies and higher pregnancy rates.     

Monitoring of menstrual cycles, ovulation, and adrenal suppression by saliva sampling in female patients with 21-hydroxylase deficiency

OBJECTIVE: To investigate the correlation between menstrual cycles, ovulation, and adrenal suppression in congenital adrenal hyperplasia. DESIGN: Prospective observational study. SETTING: An academic outpatient clinic. PATIENT(S): Five females with salt-wasting 21-hydroxylase deficiency, aged 15.5 to 22.9 years; one had amenorrhea, one had irregular bleeding, and three had regular bleeding. INTERVENTION(S): Daily morning saliva sampling for 40 to 280 days. MAIN OUTCOME MEASURE(S): Salivary levels of progesterone (P), 17-hydroxyprogesterone (17-OHP), and androstenedione. RESULT(S): In the amenorrheic patient, the elevated P and 17-OHP levels decreased when the glucocorticoid dose was increased, and subsequently menarche occurred. The androstenedione levels were normal. The correlations between P and 17-OHP levels before and after menarche suggest that adrenal progesterone had prevented menarche. The patient with irregular bleeding showed slightly elevated androstenedione levels and increased levels of 17-OHP and P in an irregular pattern, without correlation in time with vaginal bleeding. Three patients with regular cycles showed a biphasic pattern of P levels, indicating ovulation. CONCLUSION(S): These longitudinal data support the hypothesis that menstrual cycling in females with 21-hydroxylase deficiency can be prevented or disturbed by elevated progesterone levels of adrenal origin, in the absence of androgen excess. Increasing glucocorticoid dose could suppress adrenal progesterone production, resulting in menarche.     

Controlled ovarian hyperstimulation does not adversely affect endometrial receptivity in in vitro fertilization cycles

OBJECTIVE: To determine whether exposure of developing endometrium to supraphysiologic E2 levels during controlled ovarian hyperstimulation (COH) in IVF cycles inhibits endometrial receptivity. DESIGN: Retrospective analysis of IVF-ET and ovum donation data. SETTING: Tertiary-care teaching hospital. PATIENT(S): Four hundred ten patients <33 years of age undergoing IVF-ET and 181 anonymous ovum donors (<33 years of age) and their associated ovum recipients. MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and delivery rates. RESULT(S): Ovarian response to COH (duration of stimulation, peak E2 level, area under the curve for E2 exposure, and number of oocytes retrieved) was similar for IVF-ET patients and ovum donors. Donors were younger than IVF-ET patients (mean age, 27.5 +/- 0.2 years vs. 30.4 +/- 0.1 years). A similar number of embryos with similar number of blastomeres were transferred in IVF-ET patients and ovum recipients. The fragmentation rate at time of transfer differed slightly between groups (5.2 +/- 0.2% vs. 4.3 +/- 0.3%). Implantation, pregnancy, and delivery rates did not differ between IVF-ET patients and recipients of donor oocytes. CONCLUSION(S): Exposure of the developing endometrium to controlled ovarian hyperstimulation during IVF cycles does not inhibit embryo implantation or affect pregnancy and delivery rates.     

Accelerated endometrial maturation in the luteal phase of cycles utilizing controlled ovarian hyperstimulation: impact of gonadotropin-releasing hormone agonists versus antagonists

OBJECTIVE: To evaluate the endometrium obtained during the luteal phase of controlled ovarian hyperstimulation (COH) cycles utilizing gonadotropin-releasing hormone (GnRH) antagonists, and to compare these findings with those obtained in cycles utilizing a GnRH agonist and with artificial cycles among recipients. DESIGN: Prospective evaluation of oocyte donors. SETTING: University-based in vitro fertilization (IVF) center. PATIENT(S): Fifteen oocyte donors undergoing standard COH were enrolled in 1 of 3 COH groups, and 40 recipients of oocyte donation were used as a control group. INTERVENTION(S): Controlled ovarian hyperstimulation and endometrial biopsy. MAIN OUTCOME MEASURE(S): Histological dating of endometrial biopsies, serum estradiol (E(2)) and progesterone levels. RESULT(S): On the day of oocyte retrieval, endometrial maturation was advanced by an average of 5.8 +/- 0.4 days in the antagonist group and 5.9 +/- 0.7 days in the agonist group. This advancement persisted on day 7 postoocyte retrieval. Serum progesterone levels were elevated before human chorionic gonadotropin (hCG) administration, but remained similar in both groups. CONCLUSION(S): Controlled ovarian hyperstimulation is associated with elevated progesterone levels in the late follicular phase and accelerated endometrial maturation in the subsequent luteal phase. No significant differences exist between preretrieval serial serum progesterone levels and luteal phase endometrial histology between cycles utilizing GnRH agonists or antagonists.     

Use of a gonadotropin-releasing hormone antagonist for endometrial maturation and synchronization in an ovum recipient

OBJECTIVE: To report the novel use of hMG and the GnRH antagonist for endometrial preparation and synchronization in a woman participating in an ovum donation program who was resistant to endometrial preparation with estrogen replacement. DESIGN: Case report. SETTING: Tertiary fertility center. PATIENT(S): The patient had inadequate endometrial maturation, as determined by pelvic ultrasound (thickness of <5 mm), after estrogen replacement. Ovarian hyperstimulation with hMG and a GnRH antagonist resulted in an endometrial thickness of 7.5 mm. Synchronization with a ovum donor resulted in a delivered twin gestation. INTERVENTION(S): : Late follicular transvaginal ultrasound. MAIN OUTCOME MEASURE(S): Appropriate endometrial maturation and pregnancy. RESULT(S): Appropriate endometrial maturation. CONCLUSION(S): For women with inadequate endometrial maturation with simple estrogen replacement, ovarian hyperstimulation with hMG and a GnRH antagonist can yield appropriate endometrial maturation for pregnancy through ovum donation.     

Early pregnancy losses in in vitro fertilization and oocyte donation

Objective: To evaluate prospectively the incidence of early pregnancy losses (before menstruation occurs) in IVF and ovum donation cycles.

Design: Prospective case-control study.

Setting: Tertiary care, university-associated center.

Patient(s): One hundred forty-five patients undergoing IVF and 92 undergoing oocyte donation were recruited. The control group for IVF consisted of 15 ovum donors who had no ET and were instructed to avoid intercourse. The control group for oocyte donation included 10 women undergoing a mock cycle of steroid replacement.

Intervention(s): Starting on day 6 after ET, the women were instructed to collect the first urine sample of the day every 2 days. Each patient collected six different specimens of urine (days 6, 8, 10, 12, 14, and 16 after ET for cases or the same days without ET for controls.

Main Outcome Measure(s): β-HCG was measured with a standardized microparticle enzyme immunoassay, and IVF reproductive outcome was assessed.

Result(s): For IVF, positive implantation was registered in 88 of 145 cycles of embryo replacement (60.7%). Only 30 (20.7%) resulted in viable pregnancies, whereas the remaining 58 miscarried. Forty-two of these miscarriages (72.4%) were early pregnancy losses and 13 (22.4%) were classified as clinical abortions. In ovum donation, positive implantation was recorded in 64 of 92 cycles of ET (69.6%). A total of 30 (32.6%) ended in viable pregnancies, whereas the remaining 34 (37.0%) were miscarriages. Early pregnancy loss accounted for 70.6% of pregnancy losses, whereas biochemical pregnancies and clinical abortions accounted for 11.8% and 17.6%, respectively.

Conclusion(s): Our results demonstrate that patients undergoing assisted reproductive technology have an increased rate of early pregnancy loss compared with fertile patients. In addition, these data indicate that implantation is more frequently impaired in IVF than in oocyte donation cycles, resulting in a high incidence of early pregnancy loss. This suggests that implantation may be subjected to abnormal conditions in assisted reproduction.     

Turner's syndrome and oocyte donation

This paper reviews literature about oocyte donation for patients with Turner's syndrome and reports the experience of our center. Before contemplating pregnancy, it is essential to perform a careful evaluation of the cardiovascular system, the renal system, the thyroid status and the glucose tolerance. Different studies have reported a suboptimal response of the endometrium of women with Turner's syndrome to oestrogen therapy, and suggested that higher doses of estrogens may be necessary to achieve appropriate endometrial preparation. Pregnancy rate per transfer following oocyte donation is around 30% for patients with Turner's syndrome, comparable to the one observed for patients with other conditions requiring oocyte donation. Miscarriage rate is however higher (40-50%) after oocyte donation in Turner's syndrome, and could be related to the presence of a hypoplastic uterus along with hypovascularization. During pregnancy, cardiovascular complications are potentially the most severe, such as the exacerbation of a preexisting hypertension and the dissection of aortic aneurysms. There is a high rate of Caesarean section among Turner's syndrome patients, the main reason being fetopelvic disproportion. Regarding the increased obstetrical risks in Turner's syndrome patients, the selective transfer of one embryo should ideally be performed in order to avoid additional risks associated with multiple pregnancies. In our center, 9 patients with a Turner's syndrome had 15 cycles of oocyte donation. Five pregnancies were obtained among which three were evolutive. The outcome of oocyte donation cycles were comparable for patients with a Turner's syndrome and for patients with other indications of oocyte donation.     

A follow-up study with oocyte donors exploring their experiences, knowledge, and attitudes about the use of their oocytes and the outcome of the donation

OBJECTIVE To learn what information oocyte donors were given and wanted to have about the use of their oocytes and the outcome of the donation. DESIGN: In-depth interviews. SETTING: Participants recruited through IVF clinics, matching agency, the Internet, word of mouth, and newspaper ads. PARTICIPANT(S): Thirty-three former oocyte donors and six women preparing to donate. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): Thirty-three former donors completed 66 donation cycles; 48 donation cycles were anonymous. Only 41% (16 of 39) of all participants were comfortable giving the recipient couple complete dispositional authority over the resulting embryos; the remainder wanted some control. One quarter did not want embryos used for research. Fifty-four percent (21 of 39) thought donation of excess embryos to another couple was acceptable, but one third wanted to be informed. Of the 25 anonymous donors, 6 learned the outcome of the donation; 14 others wanted to know. All hoped the donation was successful. CONCLUSION(S): Because oocyte donors' need for information varies, clinics should consider being more flexible in their disclosure policies. Disclosure about the possible uses of donor oocytes or embryos should be mandatory. Findings have implications for the informed consent and counseling processes.     

Ovum donation--a simplified approach

To date, ovum donation (OD) has involved luteinizing hormone (LH) synchronization between recipient and donor for normally cycling women, and a complex steroid replacement regimen given on a sequential and incremental basis for women with primary or secondary ovarian failure. The authors designed a simple hormonal regimen applicable to both normally cycling women starting early in the cycle, and to those with ovarian failure. It consists of administering 2 mg estradiol (E2) valerate orally three or four times daily, augmented with either 100 mg progesterone (P) in ethyl oleate intramuscularly daily or 100 mg oral progesterone (P) orally three times daily, starting on the day preceding the recovery of the donated oocytes. Gamete intrafallopian transfer procedure was undertaken for women with patent tubes and in vitro fertilization for those with obstructed tubes. The authors report their preliminary experience with 17 women who underwent ovum donation.     

Influence of paternal age on assisted reproduction outcome

There has been an increasing tendency to delay parenthood in developed countries in recent years, and there is not enough information available regarding the effect of this on fertility. The aim of this work was to determine the role of paternal age on the outcome of assisted reproduction. A retrospective study was designed comprising a total of 2204 intrauterine insemination (IUI) cycles, 1286 IVF cycles and 1412 IVF cycles with donated oocytes during the period 2000 to 2006. Male mean age was 34.3 years (range 25-56) for IUI, 34.8 years (range 19-62) for IVF and 41.10 years (range 25-71) for ovum donation cycles. Statistics revealed no differences regarding pregnancy and miscarriage rates when the results were compared among age groups. In standard IVF and ovum donation cycles there was no clear association between embryo quality and paternal age. There was no significant relationship between male age and implantation rate. So far this is the largest study concerning the relevance of male age in assisted reproduction. As confirmed by the present data, the effect of the age of the male in the range studied is irrelevant. This finding contributes to the information that can be provided to infertile couples.     

Successful pregnancy and delivery after delaying the initiation of progesterone supplementation in a postmenopausal donor oocyte recipient

Progesterone luteal support has become a standard procedure during IVF cycles. Donor egg cycle women without inherent ovarian function require complete hormone replacement, in contrast with women undergoing IVF in which luteal support is used to supplement endogenous progesterone production. Progesterone support is clearly beneficial, although the timing of its initiation can affect overall outcomes. This paper describes a case in which a postmenopausal woman attending for oocyte donation did not receive her first progesterone injection at the correct time. Treatment with progesterone began when she arrived for the transfer of the donor embryos. The two embryos were maintained in culture and one was transferred on day 6 when the delayed progesterone administration had induced a secretory transformation in her endometrium. A single gestation sac was recorded 8 weeks later, and a healthy baby was subsequently born. On the morning of day 6, delayed progesterone supplementation had induced the secretory endometrial transformation typical of the second phase of the menstrual cycle.     

受卵体外受精-胚胎移植治疗结局分析

目的:探讨受卵体外受精-胚胎移植(IVF-ET)治疗结局和疗效。方法:回顾分析2004年9月至2005年11月在本中心接受卵子赠送IVF-ET的患者共21周期的临床资料。赠卵组(20例)均采用长方案控制性超排卵行IVF-ET。受卵组(21例)采用激素替代治疗准备子宫内膜。赠卵者所赠卵子与受卵者丈夫精液行IVF-ET。选择同期常规IVF-ET患者55例做对照。结果:赠卵组种植率和临床妊娠率(7.3%,15.79%)明显低于受卵组(34.9%,52.38%)和同期IVF-ET组(21.19%,34.55%),P<0.05。结论:受卵IVF-ET是治疗卵巢功能不良和遗传原因不能生育健康后代妇女的有效方法;激素替代周期的种植率和临床妊娠率高于控制性超排卵周期。     

Significance of one pronucleus before fertilization

OBJECTIVE: To describe a case of primary infertility associated with oocytes having one pronucleus before fertilization on repeated IVF attempts. DESIGN: Case report. SETTING: A university-based assisted reproduction unit. PATIENT(S): A 30-year-old woman with primary infertility and oocytes containing one pronucleus before fertilization. INTERVENTION(S): Oocyte donation. MAIN OUTCOME MEASURE(S): Pregnancy. RESULT(S): Conceived triplets after transfer of three embryos using donor oocytes. CONCLUSION(S): This patient's infertility was likely associated with an oocyte abnormality, as evidenced by the premature formation of one pronucleus before fertilization. In the future, more studies on the appearance of a single pronucleus before fertilization will be needed to determine its overall significance on fertility.     

Pregnancy outcome of in vitro fertilization/intracytoplasmic sperm injection with profound teratospermia

OBJECTIVE: To assess the pregnancy outcome of IVF with intracytoplasmic sperm injection (ICSI) in couples with profound teratospermia (Kruger's strict criteria of zero). DESIGN: Retrospective analysis of 545 consecutive cycles of IVF/ICSI performed between January 2000 and January 2003. SETTING: Tertiary care center. PATIENT(S): Of 545 IVF/ICSI cycles, 45 patients were identified with a semen strict morphology of 0 using Kruger's strict criteria. INTERVENTION(S): Ovarian down-regulation (Lupron) was followed by controlled ovarian stimulation exclusively with hMG. Embryo transfer was performed 2 days after transvaginal aspiration/ICSI. MAIN OUTCOMES MEASURE(S): Pregnancy outcomes and newborn/infant status. RESULT(S): Of 45 patients undergoing 54 treatment cycles, 21 patients were positive for pregnancy (38.9% pregnancy/cycle). No birth defects were noted at time of delivery and all infants had obtained appropriate developmental milestones at 1 year of age. CONCLUSION(S): Men with profound teratospermia (Kruger's strict criteria of zero) may achieve acceptable pregnancy rates after IVF/ICSI thereby alleviating the use of donor sperm in this group. Furthermore, no increased risk of birth defects is apparent in this small series.     

Oocyte quality in polycystic ovaries revisited: Identification of a particular subgroup of women

Purpose: Our purpose was to assess the endocrine status of women with polycystic ovaries (PCO) undergoing IVF, and to compare oocyte quality with endocrine markers of the syndrome, in an attempt to define a subpopulation with poor quality oocytes. Methods: This was a retrospective study. Patients were first endocrinologically analyzed: serum levels of androgens (T, androstenedione, DHEAS), FSH, and LH as well as glucose and insulin after an oral glucose tolerance test (OGTT) were recorded and are expressed as absolute values and area under the curve (AUC). Subsequently, they were followed over a 2-year period in which patients underwent several attempts of IVF as well as serving as oocyte donors. Patients were divided into three groups: group I (n=4) was women who displayed embryos unable to implant in 15 IVF cycles and 10 ovum donation cycles in which they served as donors; group II (n=16) was PCO patients in whom IVF (n=38) and/or oocyte donation cycles (n=42) resulted in pregnancies; and group III (n=13) was IVF patients with normal appearance of the ovaries by ultrasound. The endocrine status was compared with the IVF results. Results: There was no difference among groups in the endocrinological parameters tested, except for the OGTT which identified women in group I as having higher serum glucose and insulin levels than patients in groups II and III. Similarly, the OGTT showed higher serum glucose values in group II compared to group III. Women in group I were also obese. Patients in group III were older than PCO patients and needed more gonadotropins to reach an ovarian response which resulted in a reduced number of oocytes retrieved. Fertilization was also impaired in group I, in which no pregnancy was recorded. Conclusions: This study shows that there is a particular subgroup of PCO patients with lower fertilization rates and embryos unable to implant. These patients are obese and nonhyperandrogenic and show derangements of insulin secretion.     

Leptin levels vary significantly during the menstrual cycle, pregnancy, and in vitro fertilization treatment: possible relation to estradiol.

OBJECTIVE: To evaluate the influence of sex steroids on leptin levels in patients with conditions in which the steroid levels are increased. DESIGN: Prospective study. SETTING: A hospital unit for reproductive medicine and a maternal care unit affiliated with the hospital and hospital staff. PATIENT(S): Thirteen women with regular menstrual cycles, 29 women with normal pregnancies, and 25 women undergoing IVF treatment. INTERVENTION(S): Blood samples were obtained during days 1-3, 6-8, 13-15, and 22-25 of the menstrual cycle in regularly cycling women and during gestational weeks 13, 20, 28, 32, and 36 and 7-13 weeks after birth in pregnant women. In women undergoing IVF treatment, blood samples were collected after E2 suppression, after ovarian stimulation, and at the time of ovum pickup. MAIN OUTCOME MEASURE(S): Serum levels of leptin, E2, and progesterone. RESULT(S): Leptin levels varied during the menstrual cycle and were elevated during pregnancy, with a peak during week 28. In the IVF group, leptin levels increased throughout the treatment cycle. Body mass index correlated positively with leptin levels in all three groups, and the maternal weight gain from weeks 13-32 tended to correlate with the rise in leptin levels. Estradiol levels correlated positively with leptin levels during E2 suppression. Negative correlations existed between the pregnancy-induced increases in E2 and leptin levels from weeks 13-32, and between the levels after birth. Leptin levels and progesterone levels did not correlate in any of the groups. CONCLUSION(S): Modest elevations of leptin levels were observed during IVF treatment and pregnancy. The increase in the IVF group indicates that factors other than body fat mass (possibly E2) also are of importance for the regulation of leptin levels.     

Successful pregnancy in a pure gonadal dysgenesis with karyotype 46,XY patient (Swyer's syndrome) following oocyte donation and hormonal treatment.

A pregnancy obtained in a patient with 46XY gonadal dysgenesis (Swyer's syndrome) after ovum donation and IVF/ET is described. The efficacy of this technique in overcoming particular cases of otherwise irreversible infertility is discussed.     

An analysis of the variation of plasma concentrations of placental protein 14 in artificial cycles.

OBJECTIVE: To analyze the factors affecting the variation of plasma concentration of placental protein 14 (PP14) in artificial cycles. DESIGN: The effects of different hormone replacement therapy (HRT) regimens were examined in a crossover design. SETTING: Jessop Hospital for Women, Sheffield, United Kingdom. PATIENTS: Eighteen women with premature ovarian failure: 6 associated with Turner's syndrome and 12 with idiopathic premature ovarian failure. INTERVENTIONS: Four different HRT regimens; 36 study cycles. MAIN OUTCOME MEASURES: Plasma PP14 concentrations on days 1, 15, 19, and 29 of the artificial cycles. RESULTS: In cycles treated with a standard HRT, the levels were similar to those of the natural cycle. Subjects with Turner's syndrome did not have elevated PP14 levels, whereas the majority (9/12 [75%]) of those with idiopathic premature ovarian failure had elevated levels on day 29 of the cycle. Levels of PP14 were reduced when either the doses of estradiol valerate were reduced to 1/3 or the doses of progesterone (P) were reduced to 1/5 of the standard HRT. CONCLUSIONS: Plasma levels of PP14 are dependent not only on P stimulation but also on adequate estrogen priming.     

Factors that determine discordant outcome from shared oocytes

OBJECTIVE: To investigate the factors that may be related to pregnancy in oocyte recipients who shared oocytes from the same donor and showed discordant pregnancy outcome. DESIGN: Matched pair analysis. SETTING: IVF academic center. PATIENT(S): Five hundred forty-two oocyte donation cycles that shared oocytes from 197 donors with discordant outcome. INTERVENTION(S): Egg donation and embryo transfer. MAIN OUTCOME MEASURE(S): Pregnancy rate and implantation rate. RESULT(S): Three hundred sixty-five matched-paired discordant outcome oocyte recipients were analyzed. Pregnant and nonpregnant recipients were similar in terms of age, serum E(2) levels, endometrial thickness, indications for oocyte donation, and abnormal sperm parameters. No differences were found in the number of oocytes received per patient, fertilization rate, IVF/intracytoplasmic sperm injection (ICSI) distribution, embryo quality, or on embryo transfer difficulty. CONCLUSION(S): Discordant pregnancy outcome could not be explained by the different egg recipients and cycle factors studied. In addition to chance, other factors must be investigated that could explain discordant outcome in egg recipients sharing oocytes from single donors.