Thelma M. Macaso

In vitro fertilization in unstimulated cycles: the University of Southern California experience*

OBJECTIVE To describe the clinical experience of our center with in vitro fertilization (IVF) in unstimulated cycles and to provide a comparison to stimulated cycles. DESIGN Spontaneous ovulatory cycles were triggered with human chorionic gonadotropin in the midcycle, and 78 aspirations for IVF were performed, with the remainder of the IVF cycle proceeding in a standard manner. SETTING The IVF program of the University of Southern California and the California Medical Center, Los Angeles, California. PATIENTS Spontaneously ovulatory women (n = 46) with predominantly pelvic factor as their principal cause of infertility, under the age of 40, and no male factor. INTERVENTIONS Human chorionic gonadotropin administration in midcycle, follicle aspiration, IVF, and embryo transfer. MAIN OUTCOME MEASURES Embryo implantation and pregnancy. RESULTS Seventy-eight follicle aspirations resulted in 11 clinical (14%) and 9 ongoing (12%) pregnancies. The per embryo implantation rate was 13% clinical and 11% ongoing. There was no decrease in per cycle pregnancy rates (PRs) for up to three unstimulated cycles. CONCLUSIONS Unstimulated IVF is a viable alternative to stimulated cycles with PRs approximately one half those of stimulated cycles. It is reasonable to offer patients up to three cycles of unstimulated IVF without expecting a decrease in PRs.

Establishment of a nonanonymous donor oocyte program: preliminary experience at the university of Southern California

Transvaginal ultrasound-directed oocyte retrieval was performed on eight women functioning exclusively as gamete donors for 10 patients with ovarian failure. Donors included sisters, personal friends, and compensated participants selected by the recipient couple. Oocyte donors underwent controlled ovarian hyperstimulation and transvaginal oocyte aspiration. Thirteen initiated cycles resulted in 11 embryo transfers and six ongoing pregnancies. There were no complications, and all donors stated a willingness to undergo the procedure again. The use of nonanonymous oocyte donation appears both efficacious and efficient and is recommended as an option for achieving pregnancy in women with ovarian failure.

Oocyte and pre-embryo donation to women with ovarian failure: an extended clinical trial

The outcome of a series of pre-embryo transfers to 31 women with ovarian failure is described. Twenty six fertile women functioned as nonanonymous donors, providing oocytes for in vitro fertilization after undergoing controlled ovarian hyperstimulation and transvaginal ultrasound directed oocyte aspiration. Recipients, 24 to 44 years of age, received hormone replacement therapy before pre-embryo transfer (ET). A mean of 13.7 +/- 1.1 oocytes were obtained per aspiration resulting in the transfer of 4.5 +/- 0.2 pre-embryos to each recipient couple. Twenty-five of 47 ET resulted in pregnancy (53.2% per ET); 5 preclinical, and 20 clinical, of which 18 are ongoing or delivered. The overall implantation rate per individual transferred fresh pre-embryo was 21.1%. We conclude that oocyte donation is a safe and highly efficient means of achieving pregnancy for women with ovarian failure.

In vitro fertilization in unstimulated cycles : a clinical trial using hCG for timing of follicle aspiration

In vitro fertilization in spsontaneous ovulatory cycles triggered with hCG was associated with a high rate of oocyte retrieval and fertilization, and gave pregnancy rates in the range of national avaerages for stimulated cycles

Preovulatory follicular fluid steroid levels in stimulated and unstimulated cycles triggered with human chorionic gonadotropin.

The purpose of this study was to analyze follicular fluid (FF) samples for steroid levels from stimulated and unstimulated cycles triggered with human chorionic gonadotropin (hCG) and to assess the influence of controlled ovarian hyperstimulation and luteinizing hormone/hCG on these levels. Spontaneous ovulatory cycles were monitored with serial ultrasound examinations, and hCG 10,000 IU was given when the lead follicle was mature. Fourteen FF samples yielding fertilizable oocytes were compared with 13 FF samples from controlled ovarian hyperstimulation cycles. Progesterone (P) was higher in controlled ovarian hyperstimulation than in unstimulated cycles (9.0 +/- 1.2 micrograms/mL versus 4.4 +/- 0.6 microgram/mL; mean +/- SEM), whereas estradiol (E2) was lower (0.8 +/- 0.1 microgram/mL versus 1.3 +/- 0.2 microgram/mL), resulting in a higher P:E2 ratio (15.5 +/- 3.3 versus 4.4 +/- 0.7). Androstenedione (A), testosterone (T), and T:E2 ratios were all higher in unstimulated than controlled ovarian hyperstimulation cycles. We conclude that controlled ovarian hyperstimulation is associated with increased FF P, decreased FF E2, T, and A levels, and decreased T:E2 ratios, suggesting altered steroidogenesis and enhanced follicular aromatase activity.

Pregnancy following nonsurgical donor ovum transfer to a functionally agonadal woman

We report this countrys first nonsurgical donor ovum transfer pregnancy in a functionally agonadal woman who had received chemotherapy and radiation for Hodgkins lymphoma. For women with ovarian failure, nonsurgical uterine lavage and ovum transfer may provide an opportunity for motherhood that was not possible previously.

The significance of elevated early follicular-phase follicle stimulating hormone (FSH) levels: Observations in unstimulated in vitro fertilization cycles

AbstractObjective: Our objective was to determine the effect of elevated early follicular-phase serum follicle stimulating hormone (FSH) levels on follicle growth and oocyte maturity in unstimulated in vitro fertilization (IVF) cycles. Study Design: We compared cycles with elevated day 3 FSH levels (>20 mIU/ml) to subsequent cycles in the same patients when day 3 FSH returned to normal and to cycles among women with normal day 3 FSH levels. Patients: Seven cycles in seven patients had an elevated day 3 FSH (high-FSH group). These were compared to 11 subsequent cycles in which there was a return to a normal baseline FSH and to 13 cycles in 13 patients that entered the unstimulated protocol with a normal baseline day 3 FSH. Results: The day of human chorionic gonadotropin (hCG) administration was similar in all groups as were the serum estradiol (E2) levels. Although the high-FSH group tended to have smaller maximum follicular diameters, the difference was not statistically significant. The highest FSH level on cycle day 3 in a completed cycle was 56.2 mIU/ml. The total number of oocytes aspirated and the number of embryos obtained was similar in all groups. Whereas there were no pregnancies in the high-FSH group, 2 of the subsequent 11 normal day 3 FSH cycles resulted in clinical pregnancies. Two of the 13 patients in the normal day 3 FSH values also achieved pregnancies. Conclusions: We conclude that cycle day 3 serum FSH levels as high as 56.2 mIU/ml may be associated with apparently normal follicular growth, oocyte fertilization, and embryo cleavage in unstimulated cycles. However, pregnancies are not observed. In addition, FSH levels vary widely from cycle to cycle and elevated levels in one cycle do not necessarily imply that pregnancy may not occur in a subsequent cycle when FSH levels return to normal.

Preimplantation adoption: establishing pregnancy using donated oocytes and spermatozoa

The experience of transferring embryos produced through in-vitro fertilization (IVF) utilizing donated oocytes and spermatozoa is described. Recipients (n = 28; aged 38-59 years) received oral micronized oestradiol and i.m. progesterone and were synchronized to donors undergoing ovarian stimulation. Reasons for selecting therapy included advanced reproductive age (> 42 years; n = 21) or hypergonadotrophic hypogonadism (n = 7), combined with severe male factor infertility in 23 couples. Five women were single and without partners. Oocytes were fertilized by cryopreserved spermatozoa designated for use by the recipient. Up to five embryos were transferred transcervically. Supernumerary embryos were cryopreserved. A total of 36 aspirations produced 15.6 +/- 7.3 oocytes per retrieval. In 10/36 cycles (27.8%), embryos were available for cryopreservation. Using fresh embryos, the overall pregnancy rate was 38.9% (14/36), clinical pregnancy rate 33.3% (12/36), and ongoing/delivered pregnancy rate 30.6% (11/36). Three ongoing pregnancies were later established by transferring cryopreserved embryos. Adjusting for these events, the per aspiration overall pregnancy rate per retrieval was 47.2%, clinical pregnancy rate 41.7%, and ongoing/delivered pregnancy rate 38.9%. Implantation rates per individual embryo transferred were 16.6% following fresh embryo transfer. A viable pregnancy was achieved by 14 of 28 women (50% cumulative pregnancy rate). We conclude that using donor oocytes and donor spermatozoa is efficacious and allows couples of whom both members suffer from severe gamete abnormalities and single functionally agonadal women an effective means of achieving pregnancy.

Embryotoxicity of three commercially available powderless surgical gloves.

The one-cell mouse embryo bioassay was utilized to test the embryotoxicity of three brands of powerless surgical gloves; Pristine, Ansell, and BioGel. The Pristine gloves demonstrated no significant embryotoxicity, while the other two brands demonstrated a consistent inhibition of blastocyst development of one-cell mouse embryos.

The effect of chemiluminescent light exposure on the in vitro development of mouse embryos

Chemiluminescent lighting has recently been introduced for use in gynecologic procedures. A chemical lightstick (Cyanamid, American Cyanamid Company, Wayne, N J) containing an oxalate ester may be activated and attached onto a plastic adaptor inside a speculum blade (Speculite, Trylon Ltd., Harbor City, CA) to provide diffuse, shadowless illumination of the cervix and vagina without generating heat. The enhanced view facilitates the performance of procedures involving the uterine cervix. This property makes the lighting device especially attractive for use in the performance of embryo transfer, where excellent visualization of the ectocervix is essential. Visible fluorescent lighting has been implicated as a possible inhibitor of embryogenesis (1-3). For this reason, human embryos grown in culture following in vitro fertilization are often shielded from exposure to direct light. Similarly, direct lighting is usually kept to a minimum during the transfer of the embryos from the incubator to the patient. To test for possible detr imental effects of chemiluminescent light exposure upon cleavage and blastulation of mouse embryos in vitro, we cultured one-cell embryos in vitro after prolonged exposure to a chemiluminescent light source. One-cell embryos were assayed in the presence of either a white or a gold chemiluminescent light. A series of separate mouse experiments was performed, along with internal controls for each bioassay. Our purpose was to document the safety of this product as a lighting adjunct for laboratory and clinical use in in vitro fertilization (IVF) programs.