Comparison of embryo quality between intracytoplasmic sperm injection and in vitro fertilization in sibling oocytes.

BACKGROUND: The aim of the present study was to compare the quality of embryos derived from sibling oocytes by in vitro fertilization (IVF) or ICSI. METHODS: Consecutive patients with a less than 40% fertilization rate in a previous standard IVF cycle or with relative male factor infertility were recruited for the study. The oocytes retrieved from each patient were divided into two groups for either conventional insemination (group A) or ICSI (group B). Power analysis showed that to detect a 25% difference in the rate of high-quality embryos between the groups with a power of 0.8, at least 1,200 oocytes were needed in each group. RESULTS: One hundred seventy-seven patients were included in the study. Group A was comprised of 1,526 oocytes and group B of 1,480 sibling oocytes. As expected, the fertilization rate was significantly higher in group B than group A (67.1 vs. 43.6%, p < 0.001). No significant between-group differences were observed in cleavage rate (92.7 and 89.7%, respectively) and the rate of either grade A embryos (22.6 and 23.9%, respectively) or grade A(1) embryos (37.3 and 33.5%, respectively). However, in the subgroup of patients with relative male-factor infertility (n = 36), the rate of grade A(1) embryos was significantly higher in the IVF than the ICSI group (46.4 vs. 29.0%, respectively, p = 0.02). CONCLUSIONS: Embryo quality does not seem to be influenced by the mode of fertilization (IVF or ICSI). We assume that embryo quality depends on intrinsic factors of the gametes involved rather than on the fertilization process per se.

Pregnancy rate fluctuations during routine work in an assisted reproduction technology unit.

BACKGROUND: Fluctuations in spontaneous pregnancy rates have been observed in the general population. The purpose of this study was to evaluate whether pregnancy rates fluctuate over time in a homogeneous assisted reproduction treatment unit. METHODS: The study sample consisted of 3522 consecutive assisted reproduction cycles conducted from January 1996 to December 1999. Only fresh cycles in women <41 years old were included. All pertinent clinical data were prospectively collected on a computerized database and analysed at the end of the study. RESULTS: Throughout the 4 years of the study, monthly pregnancy rates fluctuated between 10.5 and 34.1% (mean 21.4%) per cycle, and between 13.6 and 41% (mean 27.26%) per transfer. These fluctuations did not follow any specific seasonal pattern. CONCLUSION: During routine work in an assisted reproduction treatment unit, there are random fluctuations in the pregnancy rate. This factor should be considered in studies performed in a specific time-period.

Sonographic evaluation of the puerperal uterus: correlation with manual examination.

OBJECTIVES: To document uterine involution after vaginal delivery and cesarean section by abdominal sonography and to compare the efficacy of manual examination and ultrasonography. STUDY DESIGN: Postpartum manual and sonographic assessment of uterine involution was performed in 120 patients following vaginal and cesarean delivery with an attempt to build a database of changes in uterine dimensions. The patients' reports on the intensity of uterine contractions and vaginal bleeding were compared to the results of sonographic imaging. RESULTS: Palpation revealed proper uterine involution in 80 and 25% of patients after vaginal delivery and cesarean section, respectively. It could not be performed in 2.5% after vaginal delivery compared to 50% after cesarean section. Uterine length was found to be significantly greater after cesarean section than after vaginal delivery (p = 0.0001), and the anterior uterine wall was significantly thinner than the posterior wall (p = 0.0001). Uterine length was significantly greater in the presence of blood accumulation in the uterine cavity (20.7 cm), than when the uterus was empty (18.8 cm) (p = 0.001). In correlating between the patient's report of intense bleeding and the sonographic picture of blood in the uterine cavity sonography had a sensitivity of 0.56 and a specificity of 0.83, whereas the patients' reports had a positive predictive value of 0.22. The difference in information provided by the patients versus that provided by sonography was highly significant (p = 0.001, chi(2) test). CONCLUSION: Within 3 days after delivery, patients particularly those having had a cesarean section, should undergo uterine sonographic scanning and manual palpation to evaluate involution and presence of blood in the uterine cavity.

Turner's syndrome and fertility: current status and possible putative prospects.

Women with Turner's syndrome should be carefully followed throughout life. Growth hormone therapy should be started at age 2-5 years. Hormone replacement therapy for the development of normal female sexual characteristics should be started at age 12-15 years and continued for the long term to prevent coronary artery disease and osteoporosis. Most women with Turner's syndrome have ovarian dysgenesis; therefore, they are usually infertile, and in very rare cases have spontaneous menses followed by early menopause. Only 2% of the women have natural pregnancies, with high rates of miscarriages, stillbirths and malformed babies. Their pregnancy rate in oocyte donation programmes is 24-47%, but even these pregnancies have a high rate of miscarriage, probably due to uterine factors. A possible future prospect is cryopreservation of ovarian tissue containing immature follicles before the onset of early menopause, but methods of replantation and in-vitro maturation still need to be developed. Should these autologous oocytes indeed be used in the future, affected women would need to undergo genetic counselling before conception, followed by prenatal assessment.

The polymorphic CAG repeat in the androgen receptor gene in Jewish Israeli women with endometrial carcinoma.

BACKGROUND: Endometrial carcinoma is considered a hormonal-dependent tumor; estrogen induces endometrial cellular proliferation, whereas progestins display an antiproliferative effect on endometrial tissue. The role that androgen and its receptor (androgen receptor [AR]) play in the pathogenesis of endometrial carcinoma is less clear. Although androgen has an in vitro inhibitory effect on endometrial cell proliferation, up to 75% of endometrial carcinoma express AR somatically. A polymorphic CAG repeat within exon 1 of the AR encodes for a polyglutamine tract, with length range of 8 to 33 repeats, which is inversely correlated with the transcriptional activity of the AR. METHODS: To gain insight into the role of AR in endometrial carcinoma, the authors analyzed the polymorphic CAG repeat in 79 Jewish Israeli patients with endometrial carcinoma as compared with 44 healthy Jewish women serving as controls. Analysis was conducted using germline DNA as template and using polymerase chain reaction primers flanking the CAG repeat with subsequent fluorescent determination of allele sizes. RESULTS: Allele size range of the longer of the two alleles in the patients was 11-33 (mean, 19.8 +/- 2.7) and in the controls 10-22 (mean, 17.9 +/- 1.9), a statistically significant difference (P < 0.01). Allele size variation within the patient group did not correlate with disease stage, grade, reproductive history, or age at diagnosis. CONCLUSIONS: The authors conclude that AR-CAG repeat length differs in Jewish patients with endometrial carcinoma as compared with healthy individuals in Israel, and this finding increases the possibility that the AR is involved in the predisposition to this neoplasm.

Triple-test screening in in vitro fertilization pregnancies.

PURPOSE: To determine whether the results of triple-test analysis differ between spontaneous and IVF pregnancies. METHODS: The study population consisted of 140 women with singleton pregnancies, 70 by IVF, and 70 by spontaneous conception. The groups were matched for maternal age, gestational week, and laboratory batch. The levels of all triple-test markers--alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), and unconjugated estriol (u-E3)--were compared between the groups. RESULTS: Significantly higher HCG levels were detected in the patients with IVF pregnancies than in the control group (1.31 +/- 0.8 vs. 0.95 +/- 0.5 multiple of the medians, respectively, (p < 0.006), but there were no significant differences in AFP or u-E3 levels. Overall, 18.5% of the IVF group were found to be screen-positive as compared with 11.4% of the control group (difference not statistically significant). Only 8 IVF pregnancies (11.4%) reached the lowest calculated risk possible (1:9999) compared with 17 (24.2%) in the control group (p < 0.05). CONCLUSIONS: Our findings support previous data demonstrating elevated maternal serum HCG in IVF patients in comparison with spontaneous ones.

Are singleton assisted reproductive technology pregnancies at risk of prematurity?

PURPOSE: Our purpose was to determine the risk of premature delivery among singleton pregnancies derived from assisted reproduction technology (ART). METHODS: Ninety-five singleton ART pregnancies and 190 matched spontaneous pregnancies were assessed for preterm delivery rates, pregnancy complications, and cesarean section rates in a retrospective study at an academic medical center. RESULTS: Among the ART singleton deliveries group (n = 95), 19 (20%) were preterm, which was statistically significantly higher than the 4% (8 of 190) found in the control group. Among the pregnancies achieved by intracytoplasmic sperm injection (ICSI) in the severe male-factor infertility subgroup (n = 22), only one preterm delivery occurred (4.5%). CONCLUSIONS: Singleton ART pregnancies are at an increased risk of preterm delivery compared to singleton pregnancies after spontaneous conception. The higher rate may be attributed to various infertility cofactors, such as uterine malformations, previous operative procedures that involved cervical dilatation, and a history of pelvic infection. This is supported by the finding that ICSI-derived pregnancies in couples with strict male-factor infertility are not at an increased risk of preterm delivery.

Influence of hormone replacement therapy on postmenopausal pelvic organs.

OBJECTIVE: To assess the influence of hormone replacement therapy (HRT) on the pelvic organs of postmenopausal women by vaginal ultrasonography. DESIGN: The study (case-control) included 753 consecutive, postmenopausal women who were referred for routine transvaginal ultrasound examination. A total of 290 women who were using HRT at the time of examination (study group) were compared with 463 who were not treated (control group). RESULTS: The women using HRT were younger and had been menopausal for a shorter period, compared with those who had not been treated. Mean uterine volume, endometrial thickness and ovarian area were all increased in the HRT group, compared to the control group. A negative correlation was found between menopausal age and uterine volume, and ovarian area in both treated and untreated groups. However, endometrial thickness was negatively correlated with menopausal age in the untreated group only. After controlling for various parameters, a multivariate logistic analysis demonstrated that endometrial thickness was treatment status-dependent only. Uterine volume was also treatment status-dependent, but was also negatively correlated with menopausal age. As expected, the endometrium was thicker and the uterine volume was larger in the treated group. Ovarian area was not found to be treatment-dependent for all menopausal ages. CONCLUSIONS: Postmenopausal women treated with HRT have a larger uterus and thicker endometrium than those of non-treated matched controls. There is a negative correlation between menopausal age and uterine and ovarian size. Endometrial thickness was found to be negatively correlated with menopausal age in only the untreated group, and is almost entirely HRT-dependent. In contrast to the uterus and the endometrium, the ovaries are not influenced by HRT.

Ultrasound-guided testicular sperm aspiration in azoospermic patients: a new sperm retrieval method for intracytoplasmic sperm injection.

PURPOSE: We investigated the technique of ultrasound-guided testicular sperm aspiration (USTSA) and compared it with "blind" testicular sperm aspiration (TSA) in patients with nonobstructive azoospermia. METHODS: Thirty-nine consecutive azoospermic men underwent TSA, 16 under sonographic guidance (USTSA group) and 23 with no imaging guidance (TSA group). Clinical and hormonal evaluation and sonography of the scrotum and testes were performed 1-2 days before the procedure. The aspiration was done using short-term general anesthesia. Follow-up consisted of sonographic reexamination of the scrotum and testes immediately and 1 month after the procedure. RESULTS: Intraoperative sonography with power Doppler imaging enabled good visualization of the testicular parenchyma, easy sampling, and avoidance of prominent vessels. Sufficient material was retrieved in 15 USTSA patients (94%) and 19 TSA patients (83%). No patients needed more than 4 hours' ambulatory hospitalization after the procedure. In the remaining 5 patients, aspiration failed to yield sperm, so open biopsy was performed. In those patients, postaspiration surgical exploration revealed subtunical bleeding in 3 patients after TSA but none after USTSA. Late minor complications occurred in 2 patients (13%) in the USTSA group and 7 (30%) in the TSA group. No difference was found between the 2 groups in pregnancy rate in the patients' female partners. CONCLUSIONS: USTSA is a safe and accurate method for sperm retrieval in azoospermic patients.

A randomized, double-blind clinical trial using fixed daily doses of 100 or 200 IU of recombinant FSH in ICSI cycles.

The effect of 100 and 200 IU per day recombinant FSH (rFSH) on numbers of oocytes retrieved and the total dose used in ovarian stimulation before intracytoplasmic sperm injection was investigated in a double-blind, randomized multicentre trial. A total of 91 women was treated with a low-dose protocol and 88 with a high-dose regimen at five centres. For each started cycle, significantly more oocytes were retrieved in the 200 IU group than in 100 IU group (12.0 versus 5.7, P < 0.001); total rFSH consumption was 1121 and 1875 IU in the low- and high-dose groups respectively. Significant variations were noted between centres with regard to numbers of oocytes collected per started cycle, ranging from 2.8 to 7.2 in the 100 IU group and from 9.0 to 19.1 in the high-dose group. Exploratory analyses of secondary outcomes suggested there were no differences in vital pregnancy rates per started cycle (19.2 versus 16.9%) and per embryo transfer (26.2 versus 19.3%) in the low- and high dose groups respectively. There were four hospitalizations due to ovarian hyperstimulation syndrome, all in the 200 IU group.

Soluble L-selectin levels during controlled ovarian hyperstimulation.

We sought to determine whether neutrophil activation, as reflected by soluble L-selectin levels, plays a role in controlled ovarian hyperstimulation (COH) and the possible correlation between soluble L-selectin and serum sex steroid levels. The study population consisted of 14 consecutive patients undergoing our routine in vitro fertilization (IVF) long gonadotropin-releasing hormone (GnRH) analog protocol. Blood was drawn three times during the COH cycle: (1) on the day when adequate suppression was obtained (Day-S); (2) on the day of, or the day prior to, human chorionic gonadotropin (hCG) administration (Day-hCG); and (3) on the day of ovum pick-up (Day-OPU). Levels of sex steroids and plasma soluble leukocyte selectin (L-selectin) were compared among the three time points. Soluble L-selectin was measured with a commercial sandwich enzyme-linked immunosorbent assay (ELISA). The results showed significantly higher levels of soluble L-selectin on Day-OPU than on Day-S and Day-hCG, and significantly lower levels on Day-hCG than Day-S. Though no significant correlations were found between soluble L-selectin and serum estradiol or hCG levels, soluble L-selectin positively correlated with serum progesterone levels. We conclude that hCG administration leads to neutrophil activation, which correlates with the degree of luteinization. Further studies are required to elucidate the relationship between the immune system and COH. These may lead to new strategies for predicting and preventing complications of COH.

Real-time intraoperative ultrasound guidance: the transrectal approach.

OBJECTIVE: To assess the role of real-time transrectal ultrasound guidance in complicated gynecologic procedures. DESIGN: In 1998-99, real-time guidance with transrectal ultrasound was utilized in our department to assist the gynecologic surgeon in two procedures: completing the evacuation of the uterine cavity after identification of uterine wall perforation during first trimester termination of pregnancy, and drainage of infected vaginal vault hematoma following hysterectomy. RESULTS: The technique was applied for 11 patients, six abortions and five infected hematomas. All the procedures were completed without any further complications and the patients were discharged on the following day. Follow-up was uneventful. CONCLUSIONS: On-line intraoperative transrectal ultrasound can effectively provide real-time assistance to the gynecologic surgeon during complicated pelvic procedures.

Effect of thrombophylaxis on uterine and fetal circulation in pregnant women with a history of pregnancy complications.

PURPOSE: The aim of this study was to investigate the effect of thromboprophylactic therapy on fetal and maternal Doppler flow parameters in pregnant women with severe complications in previous pregnancies and evidence of acquired or congenital thrombophilia in the current pregnancy. METHODS: Sixty-five patients with a history of recurrent abortions, intrauterine fetal death, intrauterine growth restriction (IUGR), and severe early-onset preeclampsia were tested for the presence of acquired or congenital thrombophilia. Those with positive findings were prescribed low-dose aspirin plus low-molecular-weight heparin (LMWH) (enoxaparin); the remainder received low-dose aspirin only. A Doppler flow study was performed before and after treatment and in the third trimester of pregnancy. RESULTS: Of the 65 pregnancies, four ended in spontaneous abortion and were excluded from the analysis. Of the 61 women with completed pregnancies, 37 (61%) had evidence of acquired or congenital thrombophilia: 22 (36%) protein S deficiency; 1 (2%) protein C deficiency; 2 (3%) activated protein C resistance (APC-R); 2 (3%) IgG for antiphospholipid antibodies; 1 (2%) circulating anticoagulant; and 9 (15%) a combined defect. This group showed a significant decrease in mean uterine artery pulsatility index (PI) before and after treatment (1.32+/-0.36 vs. 1.04+/-0.23, P=.006), whereas the remaining 24 patients treated with low-dose aspirin only had nonsignificant changes. Pearson's correlation test yielded no correlations of the pregnancy outcome parameters with Doppler flow values in the umbilical or uterine arteries. CONCLUSIONS: Thromboprophylactic therapy transiently improves maternal circulation parameters in patients with thrombophilia at risk of fetal loss and other severe complications of pregnancy, but not in correlation with their pregnancy outcome. Therefore, Doppler examination of maternofetal circulation in the second trimester is not predictive of pregnancy outcome.

10% hydroxyethyl starch for plasma expansion in the treatment of severe ovarian hyperstimulation syndrome. A case report.

BACKGROUND: Severe ovarian hyperstimulation syndrome is a complication of hormonal therapy for in vitro fertilization and carries the risk of renal failure. The injection of 6% hydroxyethyl starch has been used as a preventive measure. CASE: A 33-year-old woman was admitted with severe ovarian hyperstimulation syndrome after receiving gonadotropins as part of our in vitro fertilization protocol. Despite treatment with saline, albumin and abdominal taps, oliguria developed on the third day. The patient was transferred to the general intensive care unit and treated with 10% hydroxyethyl starch, furosemide and a further abdominal tap. Recovery was rapid. CONCLUSION: Ten percent hydroxyethyl starch is an efficient plasma expander. It is safe, biohazard free and cost-effective. It seems to effectively control severe ovarian hyperstimulation syndrome and to overcome acute prerenal failure. Larger prospective studies are necessary to further evaluate its role in the treatment of severe ovarian hyperstimulation syndrome.

Morphological study of fully and partially isolated early human follicles.

OBJECTIVE: To compare the development of fully and partially isolated human follicles by using various culture systems. DESIGN: Human ovarian material was incubated with collagenase and deoxyribonuclease. Fully and partially isolated follicles (30-50 microm) were dissected and studied under light and electron microscopy. The follicles were then cultured on and within various matrices. Fully isolated follicles were also cocultured with stromal cells. SETTING: Rabin Medical Center, a major care and referral center. PATIENT(S): Women undergoing laparoscopy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Microscopy studies, follicular measurements. RESULT(S): Electron microscopy studies revealed an excess of lipid droplets in the granulosa cells of freshly isolated follicles. An increase in follicular size and granulosa cell number was observed only in the fully isolated follicles cultured within collagen gels for 24 hours. Most of the partially isolated follicles detached from the collagen gels. When cultured on collagen, extracellular matrix, and poly-L-lysine, both the fully and the partially isolated follicles deteriorated within the first 24 hours; coculture with stromal cells had no beneficial effect. CONCLUSION(S): The excess in lipid droplets in granulosa cells of isolated follicles might suggest that the isolation process does not yield completely healthy follicles. However, despite this finding, our studies show that fully isolated follicles, but not partially isolated follicles, can grow within, but not on, a culture matrix.

Hospitalization for early bonding of the genetic mother after a surrogate pregnancy: report of two cases.

BACKGROUND: In surrogate pregnancies the genetic parents have little opportunity for early bonding to their infant, either prenatally (in utero) or in the immediate postnatal period. The purpose of this article is to describe a new method for encouraging early parent-infant bonding after surrogate pregnancy by hospitalizing the genetic mother in the maternity ward immediately after the delivery. METHODS: Two genetic mothers were hospitalized in the maternity ward (rooming-in system) at the Rabin Medical Center in Israel immediately after delivery of their infants by surrogate arrangement. The first birth was a singleton pregnancy with vaginal delivery and the second, a twin pregnancy with delivery by cesarean section. The genetic parents were counseled by a social worker from the adoption agency, starting 3 months before the estimated date of delivery. The parents were referred to the hospital social worker before the delivery. To assess attachment, we observed the parents' behavior toward their children during two daily 15-minute periods of free, unstructured interaction. RESULTS: The parents showed good primary caregiving functions and established affective verbal and physical contact with the infants. They began to recognize the infants' needs and temperament, and exhibited an aura of self-confidence during their interactions. All expressed satisfaction with the method at discharge and reported on reduction of their fears about returning home with the infants. CONCLUSIONS: We believe that early hospitalization of the genetic mother in a surrogate delivery may be desirable to establish good and safe early mother-infant bonding, and that it should be considered for adoption as regular hospital policy. Further randomized studies with larger samples over the long term are warranted.

Spectrum of normal intrauterine cavity sonographic findings after first-trimester abortion.

OBJECTIVE: To characterize the sonographic appearance of the uterine cavity after uncomplicated first-trimester abortion. METHODS: Women who underwent uterine evacuation for first-trimester abortion were referred for endovaginal sonographic examination within the week after the procedure. Special attention was directed to characterizing the intrauterine cavity. Demographic and clinical parameters were collected. A repeated postmenstrual examination was carried out in selected cases. RESULTS: In all, 57, 10, and 7 sonographic examinations were performed after termination of pregnancy, incomplete (spontaneous) abortion, and missed abortion, respectively. Fifty-seven (77%) of the 74 examinations showed considerable amounts of intrauterine content with various echogenicities (anteroposterior thickness range, 7-61 mm). No association could be documented between the pattern of appearance and gravidity, parity, gestational age, or type of abortion procedure. All postmenstrual reevaluations of patients with excessive amounts of intrauterine material at the initial examination (n = 7) showed empty intrauterine cavities. CONCLUSION: Within the week after first-trimester abortion, the uterine cavity is seldom empty. Thick heterogeneous material is an expected finding after examination. By being familiar with this normal range of appearances, clinicians can avoid unnecessary repeated invasive evacuation procedures. A follow-up sonographic evaluation during the follicular phase of the next menstrual cycle is recommended to confirm the absence of retained products of pregnancy.