Faculty Bibliography

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

We describe the longest-known continuous use of clomiphene citrate ever reported in a human. As a result of a pharmacy error, a woman took 50 mg/day clomiphene citrate for three months. The prolonged use of this medication resulted in ovarian hyperstimulation and unilateral oophorectomy for torsion

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

To assess the association of zona pellucida micromanipulation and subsequent development of monozygotic twins, cases of assisted embryo hatching (AH) and intracytoplasmic sperm injection (ICSI) were identified and related to treatment type, implantation and zygosity data. Embryology records from all patients undergoing in-vitro fertilization (IVF) at this centre from January 1995 to March 1998 were reviewed. In this study, 3546 transfer cycles were completed, with clinical pregnancy established in 1911 (54% per transfer) patients undergoing a single IVF cycle. These pregnancies occurred in 1674 (88%) IVF cycles, 120 (6%) donor oocyte cycles (DER), and 117 (6%) frozen embryo transfer (FET) cycles. During the study period, 23 cases of monozygotic (MZ) twins were identified, representing an overall frequency of 1.2%. Chorionicity was determined by transvaginal ultrasound at 7 weeks when the number of embryos transferred was less than the number of fetal heart-beats, or when >1 fetal heartbeat per gestational sac was seen. Zygosity was confirmed by placental evaluation at delivery, and corroborated the antenatal diagnosis in all cases. Among IVF study patients the frequency of MZ twinning was not statistically different between zona manipulated and zona intact subgroups. While this investigation is the largest to date describing the relationship between MZ twins and zona procedures, studies with even greater statistical power are needed to clarify it more precisely, particularly in DER and FET settings. A greater overall frequency of MZ twinning for IVF patients may be a function of the higher number of embryos transferred in IVF, rather than discrete zona manipulations

The human zygote relies on the paternal gamete to provide the centrosome component essential for the first mitotic division. It is not known whether normal centrosome function requires an intact spermatozoon, or whether donation of an isolated paternal centrosome component can result in normal zygotes and embryos. To explore this possibility, mature human oocytes were microinjected with either intact or dissected spermatozoa. Fertilization and cleavage rates were documented; nuclear and cytoskeletal changes were observed with fluorescent immunocytochemistry; and chromosomal normality was assessed with fluorescent in-situ hybridization. A pilot study was performed to identify cytoskeletal features suggestive of centrosome function. Unfertilized oocytes and tripronucleate (3PN) zygotes from in-vitro fertilization or intracytoplasmic sperm injection were assessed to confirm the sequence of the landmarks of human fertilization. Oocytes injected with mechanically-dissected spermatozoa appear to be capable of normal pronuclear formation and embryonic cleavage, but do not undergo normal mitotic division. Although decondensed, apposed nuclei are noted in combination with diffuse cytoskeleton assembly, no spindle was detected in any zygote resulting from the injection of a dissected spermatozoon. Analysis of selected embryos resulting from dissected sperm injection revealed chromosomal mosaicism in the majority of specimens. The lack of a bipolar spindle, in combination with chromosomal mosaicism, suggests abnormalities of the mitotic apparatus when sperm integrity is impaired following dissection

The commercial availability of highly purified, s.c. administered urinary follicle stimulating hormone (FSH) preparations for ovarian stimulation marked the beginning of a new era in the treatment of infertility. As these new formulations contain essentially no luteinizing hormone (LH), supplemental LH may be needed for optimal folliculogenesis. It was the aim of this pilot study to compare fertilization rates, embryo morphology, implantation rates and pregnancy outcomes prospectively in two age-matched patient groups: women who received highly purified FSH (FSH-HP) (n = 17), and women who received FSH-HP plus recombinant human LH (rhLH, n = 14) throughout ovarian stimulation. All patients received mid-luteal pituitary down-regulation with s.c. gonadotrophin-releasing hormone agonist (GnRHa) (leuprolide). Mean implantation rates were 26.9 and 11.9% in the FSH-HP only and FSH-HP + rhLH groups respectively. The mean clinical pregnancy/initiated cycle rate was 64.7 and 35.7% for the FSH-HP only and FSH-HP + rhLH patients respectively. FSH-HP patients and FSH-HP + rhLH patients achieved clinical pregnancy/transfer rates of 68.8 and 45.5% respectively. One patient in the FSH-HP + rhLH group had a spontaneous abortion; no pregnancy losses occurred in the FSH-HP only group. There were more cancellations for poor ovarian response among FSH-HP + rhLH patients (n = 3) than among FSH-HP patients (n = 1). The trend toward better pregnancy outcomes among patients who received FSH-HP without supplemental rhLH did not reach statistical significance. It is postulated that appropriate endogenous LH concentrations exist despite luteal GnRHa pituitary suppression, thereby obviating the need for supplemental LH administration

While the fertilising spermatozoon supplies the active centre directing the human zygote's first mitotic division, the relative contributions of the sperm head and tail (as well as the importance of the sperm's general structural integrity) to subsequent developmental processes remain incompletely studied. The sperm nucleus contains paternal chromatin necessary for restoration of a diploid genome, but the functional role of the sperm tail (either attached or dissected) in early human embryonic growth is not known. In this investigation using oocytes donated by in vitro fertilisation patients, human oocytes were injected with isolated sperm heads (n = 73), isolated sperm flagella (n = 11) or both (dissected sperm heads + free sperm tails, n = 26). The formation of bipronucleate zygotes was recorded for each method. Among oocytes surviving injection with isolated sperm heads, 44 of 66 (67%) formed two pronuclei. Of oocytes receiving only sperm tails, 2 of 11 (18%) displayed two pronuclei, but a single polar body was evident in both cases. When dissected spermatozoa parts (head + tail) were jointly injected, 12 of 26 (46%) developed two pronuclei. From embryos resulting from each of these three fertilisation regimes, blastomere biopsies were obtained and subjected to multiprobe fluorescent in situ hybridisation (FISH) analysis to detect mosaicism or aneuploidy arising from these experimental treatments. Only embryos with growth sufficient to permit sampling of at least two blastomeres were evaluated, and FISH analysis was successful in 25 of 29 (86%) embryos tested. Of 12 embryos derived from injection of an isolated sperm head, only one was normal diploid; the remaining 11 were mosaic. Both embryos resulting from injection of an unattached sperm tail were mosaic. Of 11 embryos generated from oocyte injection with sperm head + tail segments, 10 (91%) were mosaic and only one was normal diploid. Results from this study show that injection of isolated sperm segments can permit oocyte activation and bipronuclear formation. However, a high rate of mosaicism in human embryos originating from disrupted sperm or sperm components suggests that more than a 'sum of parts' is needed for later development. The structural integrity of the intact fertilising spermatozoon appears to contribute to normal human early embryogenesis

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

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