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Biomedical subjects

Zev Rosenwaks

Publications and source records attributed to Zev Rosenwaks.

At least 19 recordsLinked to original sources

Outcome of in vitro fertilization in women 45 years and older who use autologous oocytes.

OBJECTIVE: To determine the IVF outcome in women over the age of 44 years. DESIGN: Retrospective analysis. SETTING: University-based IVF center. PATIENT(S): Two hundred eighty-eight consecutive IVF cycles in women over the age of 44 years. INTERVENTION(S): IVF. MAIN OUTCOME MEASURE(S): Ovarian response and cycle outcome. RESULTS: The mean age of the patients was 45.4 (+/-0.73) years, with a range of 45-49 years. Fifty-seven of 288 (19.8%) did not start because of an elevated FSH or ovarian cyst. Just over 30% (70/231) had their cycle cancelled before retrieval. The mean number of oocytes was 6.8 (+/-3.8), and the mean number of fertilized zygotes was 5.4 (+/-3.4). On average, the mean numbers of embryos replaced were 3.2 (+/-1.5). An overall pregnancy rate of 21.1% (34/161) per retrieval was found. Of these, 85.3% (29/34) experienced a pregnancy loss. The overall delivery rate was 3.1% (5/161) per retrieval. Only patients at 45 years of age with a good response (>5 oocytes) achieved a delivery. CONCLUSION(S): We have shown that IVF is a reasonable option for women of very advanced maternal age (>44 years) but is limited to those at the age of 45 years with a response of >5 oocytes.

Age Factors↗

Immunohistochemical expression of endometrial L-selectin ligand is higher in donor egg recipients with embryonic implantation.

OBJECTIVE: To correlate L-selectin ligand (LSL) expression in human endometrium with embryonic implantation. DESIGN: Retrospective cohort analysis. SETTING: University-based fertility center. PATIENT(S): Donor egg recipients (DERs) who underwent programmed hormonal replacement for ET with prior mock cycle luteal phase endometrial biopsy. INTERVENTION(S): Immunohistochemical expression of LSL using MECA-79 antibody was examined. Slides were scored with a new scoring system, the IHC-Level (range 0-4) as follows: strength of staining-absent (0), weak (1), or strong (2); plus distribution of staining-absent (0), <50% of tissue (1), and >50% (2). Cellular apex and cytoplasm were scored independently in both the endometrial glandular and surface epithelium. MAIN OUTCOME MEASURE(S): Endometrial LSL expression in pregnant versus nonpregnant patients. RESULT(S): MECA-79 IHC-Level of the apex of surface epithelium was significantly higher for pregnant versus nonpregnant DERs (3.8 vs. 3.4). When controlling for embryo morphology, there continues to be a significant difference in apex score on surface epithelium (3.8 vs. 3.3, respectively). The new scoring system results correlated with an established scoring system, the HSCORE. CONCLUSION(S): We demonstrate significantly higher expression of LSL at the apex of human endometrial surface epithelium obtained from DERs with embryonic implantation. Furthermore, we present the IHC-Level, a method of evaluating immunohistochemistry that may be applied to other markers of endometrial receptivity.

Adult↗

Simultaneous bilateral ovarian torsion in the follicular phase after gonadotropin stimulation.

OBJECTIVE: To present and discuss the first report of follicular phase bilateral ovarian torsion following a cancelled IVF cycle. DESIGN: Case report. SETTING: University-based assisted reproductive technology program. PATIENT(S): A 41-year-old nulligravid patient on day 3 of her menses following a cancelled IVF cycle. INTERVENTION(S): Gonadotropin ovulation induction; laparoscopy with detorsion of left and right ovaries; aspiration of cysts. RESULT(S): Ovarian torsion resolved; follicular development in the following natural cycle. CONCLUSION(S): This is a unique case of simultaneous bilateral ovarian torsion following a cancelled IVF cycle and presenting in the ensuing follicular phase. Physicians should be aware of this unusual risk related to persistently enlarged ovaries in the cycle following gonadotropin stimulation. Furthermore, management of the infertility patient should be conservative and focused on ovarian preservation whenever feasible. Early surgical intervention can permit reperfusion and salvage of the affected adnexa.

Abdominal Pain↗

Correlation of somatic cell steroid secretion and quality of generated oocytes after in-vitro stimulation of mouse follicles.

PURPOSE: To test the possibility of follicular somatic cell steroidogenesis as a marker for quality of their embraced oocytes. METHODS: Mechanically isolated mouse preantral follicles were cultured and matured in-vitro (IVC/IVM) for study. RESULTS: During IVC/IVM, oogenesis occurred concomitantly with folliculogenesis in a coordinated manner and simultaneously with progressive increments of somatic cell steroidogenesis. Follicular E(2) production of matured oocytes were significantly higher than that of immature ones. The majority of MII oocytes (32/36) and all developed blastocysts(12/12) were associated with active E(2) production prior to ovulation. In this study, 18 MII oocytes met both requirements for active and optimal E(2) production. 13 of them were fertilized and 10 developed into blastocysts. CONCLUSION: Active somatic cell steroidogenesis prior to ovulation and an optimal steroid milieu at ovulation are prerequisites for generation of competent oocytes after follicular maturation in-vitro.

Animals↗

Mouse ascites Golgi mucin expression abnormalities in natural cycle endometrial biopsies predict subsequent in vitro fertilization-embryo transfer (IVF-ET) failure in patients with previous IVF-ET failures.

We performed a double-blinded retrospective cohort study to determine whether endometrial expression of mouse ascites Golgi mucin in a natural, unmedicated cycle predicts subsequent IVF-ET outcome among women with prior IVF-ET failure and poor pre-embryo quality. We found a statistically significant decrease in clinical pregnancy rate among women with abnormal mouse ascites Golgi expression, a test which was found to have high positive predictive value for failed IVF-ET.

ABO Blood-Group System↗

Hormonally active nontransformed human ovarian cell culture from oophorectomy specimens: methods of development and initial characterization.

We repeatedly established a nontransformed steroidogenically active human ovarian cell culture derived from oophorectomy specimens. The cells maintained steroidogenic activity for 3-5 passages (6-8 weeks) and responded to stimulation by insulin and gonadotropin. With pregnenolone as substrate, LH stimulated progesterone production up to 124% and FSH up to 121%. Insulin alone stimulated progesterone production up to 135%, in the presence of LH up to 191%, and in the presence of FSH up to 170%. With dehydroisoandrosterone (DHA) as substrate, insulin alone stimulated testosterone production up to 117%, and in the presence of LH (but not FSH) up to 125%. With androstenedione as substrate, insulin alone stimulated estradiol production up to 133%, FSH alone up to 188%, and LH with insulin up to 217%. With progesterone as substrate and in the presence of LH (but not FSH), 17-alpha-hydroxylase activity was stimulated up to 131%. With DHA as substrate and in the presence of LH, 3-beta-hydroxysteroid dehydrogenase (3-beta-HSD) activity was stimulated up to 139%. With androstenedione as substrate, insulin alone stimulated aromatase activity up to 202%, LH up to 208%, and FSH up to 251%. Under the same conditions, in the presence of LH and insulin, aromatase activity was stimulated up to 342%, and in the presence of FSH and insulin, up to 318%. With testosterone as substrate, insulin alone stimulated aromatase activity up to 122%. With testosterone as substrate, in the presence of LH and insulin, aromatase activity was stimulated up to 136%, and in the presence of FSH and insulin, up to 156%. Immunocytochemistry studies directly confirmed presence of aromatase and 3-beta-HSD in these cultured cells. We conclude that a steroidogenically active nontransformed long-term human ovarian cell culture can be repeatedly established from oophorectomy specimens, providing uninterrupted supply of cultured human ovarian cells for a variety of studies of ovarian physiology.

3-Hydroxysteroid Dehydrogenases↗

Success of testicular sperm extraction [corrected] and intracytoplasmic sperm injection in men with Klinefelter syndrome.

PURPOSE: The aim of this study was to report the successful fertility treatment of men with Klinefelter syndrome using testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). METHODS: A total of 42 men with Klinefelter syndrome who underwent 54 TESE procedures were identified. Before TESE, patients with serum testosterone levels less than 15.6 nmol/liter were treated with an aromatase inhibitor. Sperm retrieval rates and results of ICSI, including fertilization and clinical pregnancy, were collected. RESULTS: Mean pretreatment FSH and testosterone levels were 33.2 IU/liter and 9.8 nmol/liter. During medical therapy, the mean testosterone level rose to 17.0 nmol/liter (P < 0.01). Spermatozoa were found during 39 microdissection TESE procedures, on the day before, or day of oocyte retrieval during a programmed in vitro fertilization cycle. The sperm retrieval rate was 72% (39 of 54) per TESE attempt, and 29 of the 42 different men (69%) had adequate sperm found for ICSI. Thirty-three in vitro fertilization cycles yielded embryos for transfer in the 39 (85%) cycles with sperm retrieved. Eighteen clinical pregnancies have resulted in 21 live births [18 of 39 (46%)]. All children had a normal karyotype. CONCLUSION: TESE/ICSI is a successful intervention for the majority of patients with azoospermia and Klinefelter syndrome. Sperm retrieval and ICSI success in men with Klinefelter syndrome are comparable with other men with nonobstructive azoospermia treated at our center.

Adult↗

Ultrasound-guided trial transfer may be beneficial in preparation for an IVF cycle.

BACKGROUND: The objective of this study is to determine if ultrasound-guided trial transfer (UTT) in the office in preparation for an IVF cycle can be utilized as an alternative and/or adjunct to ultrasound-guided embryo transfer (UGET). METHODS: Patients planning to undergo an IVF cycle at an academic centre were included. Each patient underwent an UTT in the office by the same practitioner. The difference in length (DL), if any, was measured from the perceived top of the uterine cavity (catheter tip) to the actual cavity apex as visualized by ultrasound. RESULTS: Of the 64 patients enrolled, 19 patients (29.7%) had a measurable DL, of which 14 (21.9%) had a DL exists 0.5 cm, and nine (14.1%) had a DL exists 1.0 cm. Significant differences were noted between patients when comparing DL to previous pregnancy status and the total cavity depth (sounding depth + DL) (P < 0.05). CONCLUSION: UTT in the office setting appears to be beneficial in preparation for an IVF cycle with embryo transfer.

Adult↗

Fertility preservation in breast cancer patients: a prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation.

PURPOSE: To develop safe ovarian stimulation methods to perform in vitro fertilization (IVF) in breast cancer patients who wish to preserve their fertility via embryo cryopreservation before chemotherapy. PATIENTS AND METHODS: Sixty women (age range, 24 to 43 years) with breast cancer were prospectively studied. Twenty-nine patients underwent 33 ovarian stimulation cycles with either tamoxifen 60 mg/d alone (Tam-IVF) or in combination with low-dose follicle-stimulating hormone (TamFSH-IVF) or letrozole 5 mg in combination with FSH (Letrozole-IVF). After IVF, all resultant embryos were cryopreserved to preserve fertility. Recurrence rates were compared with controls (n = 31) who elected not to undergo IVF. RESULTS: Compared with Tam-IVF, both TamFSH-IVF and Letrozole-IVF patients had greater numbers of follicles (2 +/- 0.3 v 6 +/- 1 and 7.8 +/- 0.9, respectively; P < .0001), mature oocytes (1.5 +/- 0.3 v 5.1 +/- 1.1 and 8.5 +/- 1.6, respectively; P < .001), and embryos (1.3 +/- 0.2 v 3.8 +/- 0.8 and 5.3 +/- 0.8, respectively; P < .001). Peak estradiol (E2) levels were lower with Letrozole-IVF and Tam-IVF compared with TamFSH-IVF. After 554 +/- 31 days (range, 153 to 1,441 days) of follow-up, cancer recurrence rate was similar between IVF and control patients (three of 29 v three of 31 patients, respectively; hazard ratio, 1.5; 95% CI, 0.29 to 7.4), and this estimate was not affected by cancer stage. CONCLUSION: The combination of low-dose FSH with tamoxifen (TamFSH-IVF) or letrozole (Letrozole-IVF) results in higher embryo yield compared with Tam-IVF. Recurrence rates do not seem to be increased, but the letrozole protocol may be preferred because it results in lower peak E2 levels.

Adult↗

Ultrasound-guided embryo transfer and the accuracy of trial embryo transfer.

BACKGROUND: Studies have suggested that ultrasound-guided embryo transfer (UG-ET) may improve the outcome in IVF; however, several factors may account for the improvement in pregnancy rate. This study examines the use of ultrasound to determine the accuracy of trial transfer (TT) in preparation for ET. METHODS: Sixty-seven consecutive patients prospectively underwent UG-ET over a 2 month period. Total cavity length by US was compared with the length noted by TT. A difference of > or = 1 cm was considered significant. All embryos were placed within 1-2 cm of the fundus by US. RESULTS: Twenty patients (29.9%) had a difference of > or = 1 cm and 13 patients (19.4%) had a difference of < or = 1.5 cm. Patients with a difference of > or = 1 or > or = 1.5 cm had a significantly greater depth at transfer (P < 0.001) and uterine cavity length (P < 0.001) when compared with patients without a difference. Clinical pregnancy, implantation, delivery and overall miscarriage rates did not differ between patients with a difference of > or = 1 or > or = 1.5 cm versus no difference. There were no ectopic pregnancies. CONCLUSIONS: Nineteen percent of patients had a discrepancy of > or = 1.5 cm and approximately 30% had a difference of > or = 1 cm from TT at UG-ET, suggesting a benefit to UG-ET. A large prospective randomized trial comparing UG-ET with blind transfer is required to assess further if UG-ET should be used in all cases of ET.

Abortion, Spontaneous↗

Egg production predicts a doubling of in vitro fertilization pregnancy rates even within defined age and ovarian reserve categories.

OBJECTIVE: To examine the age-independent association of ovarian response and IVF outcome in women with normal and abnormal ovarian reserve. DESIGN: Retrospective analysis. SETTING: Academic IVF center. PATIENT(S): Four thousand eight hundred sixty-two consecutive IVF cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Outcome of IVF was analyzed as a function of ovarian response to controlled ovarian hyperstimulation and ovarian reserve. RESULT(S): The mean patient age was 36.2 +/- 4.5 years. Younger patients and patients with normal ovarian reserve were found to have better implantation and clinical pregnancy rates. Patients with normal ovarian reserve had a higher number of oocytes retrieved, mature oocytes, two-pronuclei embryos, and embryos transferred. A greater number of embryos were transferred for patients with higher ovarian response. Higher clinical pregnancy rates were seen in those patients who had more oocytes retrieved for all patients, regardless of age and ovarian reserve. In fact, clinical pregnancy rates more than doubled for specific patient groups. CONCLUSION(S): In an age-independent fashion, ovarian response is highly predictive of IVF outcome in women with normal and abnormal ovarian reserve. These findings highlight the importance of not solely relying on age when presenting and discussing IVF outcome data and are useful information when helping patients interpret their IVF cycle response.

Adult↗

Spontaneous ovarian hyperstimulation caused by a follicle-stimulating hormone-secreting pituitary adenoma.

OBJECTIVE: To report a case of spontaneous ovarian hyperstimulation resulting from an FSH-secreting pituitary adenoma. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 29-year-old previously healthy, nulligravid woman. INTERVENTION(S): Transphenoidal resection of the adenoma. MAIN OUTCOME MEASURE(S): Clinical remission. RESULT(S): After transphenoidal resection of the adenoma, the patient had an uneventful postoperative recovery with complete resolution of ovarian hyperstimulation and associated symptoms. Postoperative magnetic resonance imaging demonstrated residual tumor within the cavernous sinus. CONCLUSION(S): Follicle-stimulating hormone-secreting pituitary adenoma may present as acute spontaneous ovarian hyperstimulation.

Adenoma↗

Taking a basal follicle-stimulating hormone history is essential before initiating in vitro fertilization.

OBJECTIVE: To analyze IVF outcomes in patients with a history of one or more elevations in basal FSH who have a normal basal FSH at the start of their IVF cycle, compared with the general IVF population. DESIGN: Retrospective clinical study. SETTING: University hospital. PATIENT(S): General IVF patient population. INTERVENTION(S): Patients received standard IVF gonadotropin protocols, oocyte retrieval, and embryo transfer. MAIN OUTCOME MEASURE(S): Oocyte yield, fertilization, implantation, clinical pregnancy, and cancellation rate. RESULT(S): Oocyte yields were lower in patients with a history of elevated basal FSH, for all age groups, and showed an age-dependent decline in all patients. Over the age of 40 years, both implantation and clinical pregnancy rates were lower in these patients, with no significant difference observed in patients under the age of 40 years. No pregnancies were observed in patients with a history of three or more elevated FSH levels, regardless of age. CONCLUSION(S): A history of elevated basal FSH levels in patients under the age of 40 years predicts a lower oocyte yield in IVF cycles with normal basal FSH levels but does not translate to either lower pregnancy or implantation rates. Patients aged >40 years with prior elevations in basal FSH levels have both compromised ovarian response and compromised embryo quality relative to those with normal FSH levels, as illustrated by lower oocyte yield, higher cancellation rates, and lower implantation and pregnancy rates.

Adult↗

Births using sperm retrieved via immediate microdissection of a solitary testis with cancer.

OBJECTIVE: To determine the feasibility of achieving births using sperm retrieved from a solitary testis with cancer. DESIGN: Prospective clinical study of azoospermic men with testis cancer in a solitary testis. SETTING: Infertility patients in an academic environment. PATIENT(S): Azoospermic men with previous history of orchiectomy and testis cancer in a remaining solitary testis. INTERVENTION(S): Viable sperm were retrieved by immediate microdissection of paratumor testicular tissue from orchiectomy specimen. MAIN OUTCOME MEASURE(S): Live births were achieved using sperm from immediate microdissection of orchiectomy specimen with testis cancer. CONCLUSION(S): Azoospermic men with cancer in a solitary testis have potential for fertility.

Adult↗

Effect of treating induced mitochondrial damage on embryonic development and epigenesis.

Germinal vesicle transplantation (GVT) has been proposed as a possible treatment to correct age-related oocyte aneuploidy caused by dysfunctional ooplasm. How healthy ooplasm regulates normal meiosis and subsequent development has yet to be elucidated, but impaired mitochondrial metabolism may be attributable to incomplete segregation of the oocyte chromosomes. In the present study, after ooplasmic mitochondrial damage by photoirradiating chloromethyl-X-rosamine, examination of the oocyte nuclei's ability to survive after transfer into healthy ooplasts was performed. To assess their fertilizability and potential for development, GVT oocytes were fertilized by intracytoplasmic sperm injection (ICSI) and transferred to foster mice. Condition of the offspring at birth was assessed, and epigenetic analysis was performed. Photosensitization consistently inhibited oocyte maturation. However, after GVT of photosensitized nuclei into healthy ooplasts, 67.2% were reconstituted, and 76.2% of these matured normally, with an overall rate of 51.2%, much higher than that (6.0%) in the mitochondrially injured oocytes. After ICSI, 65.8% (52/79) of GVT oocytes were fertilized normally, and 21.1% (11/52) eventually reached the blastocyst stage. The transfer of 132 two-cell GVT embryos into the oviducts of pseudopregnant females resulted in 17 apparently healthy live offspring. For some key developmental genes, a high level of expression was identified in the GVT and "rescue"-derived fetal adnexa. Thus, one can induce in oocyte mitochondria a photosensitization-based type of damage, which consistently inhibits GV breakdown, meiotic spindle formation, chromosomal segregation, and polar body extrusion. Germinal vesicle transplanted and rescued oocytes were able to undergo maturation, fertilization, and embryonic cleavage and, ultimately, to develop to term. This approach may provide a model with which to study the age-related ooplasmic dysfunction seen in human oocytes.

Animals↗