Efficacy of oocytes donated by older women in an oocyte donation programme

Population and insemination studies indicate that women experiencedeclining fertility with ageing. The question therefore ariseswhether older women are suitable oocyte donors. This study addressesthis issue by examining the relationship between oocyte donorage and clinical outcome in a large oocyte donation programme.We retrospectively reviewed data from 458 consecutive oocytedonation cycles completed by 164 different designated oocytedonors. Data were divided into two groups: group A, cycles withdonors aged 21–30 years at the time of follicular aspiration(193 cycles, 88 donors); and group B, cycles with donors aged31–40 years at the time of follicular aspiration (265cycles, 86 donors). Five donors, because of ageing during repetitivedonations, contributed data to groups A and B. In a given cycle,all oocytes for a recipient came from only one designated donor.Comparing the two donor groups, there was no difference in theamount of gonadotrophin used to achieve optimal stimulation;however, more oocytes were obtained from group A than groupB donors (16.8 ± 6.9 and 15.1 ± 8.1 respectively,P < 0.05). Similar percentages of oocytes were fertilizedin each group, resulting in the transfer of comparable numbersof embryos (4.5 ± 1.1 and 4.4 ± 13 respectively).Comparable clinical pregnancy rates were achieved (group A,36%; group B, 37%). The spontaneous abortion rates were alsosimilar (group A, 20%; group B, 12%), resulting in comparableongoing and delivered pregnancy rates per cycle (group A, 29%;group B, 32%) and per embryo transferred (group A, 6.4%; groupB, 7.3%). In conclusion, women of proven fertility should notbe excluded from donating oocytes simply because of their age.There exists a cohort of fertile women who resist the decreasingfecundity and increasing spontaneous abortion rates associatedwith ageing. With careful screening, many women of proven fertilitycan donate oocytes until the age of 40 years with an efficacyequal to that of younger women. Given the relative shortageof suitable oocyte donors, and increasing requests from recipientswith previous donor oocyte babies to obtain oocytes from thesame, now older, donor, the findings of this study are of practicalclinical importance.     

Increased frequency of detection of human papillomavirus deoxyribonucleic acid in exfoliated cervical cells during pregnancy

Exfoliated cells of the uterine cervix obtained from women during pregnancy and at the time of their first postpartum examination were used to monitor the prevalence of human papillomavirus infections in this population and to study the natural fluctuations in viral expression. When deoxyribonucleic acid hybridization analysis alone was used to monitor the presence of human papillomavirus infection, 20.9% of our study population had results that were positive for human papillomavirus deoxyribonucleic acid during their first-trimester examinations. A dramatic increase in the percentage of women with positive results for human papillomavirus deoxyribonucleic acid was observed at the time of the patients' third-trimester examinations (46%). The overall increase in human papillomavirus-positive patients was a combination of a small number of patients who had positive results on their first examination and negative results on their second examination, and a larger number of patients who had negative results on their first-trimester examination and positive results for human papillomavirus deoxyribonucleic acid in the exfoliated cervical cells at the time of their third-trimester examination. The total percentage of patients with positive results for human papillomavirus deoxyribonucleic acid in their cervical cells at one or both assay points during pregnancy was 52.5%. Samples obtained at the postpartum examination demonstrated a dramatic decrease in the number of samples positive for human papillomavirus deoxyribonucleic acid (17.5%). This result was a combination of a large decrease in human papillomavirus-positive patients coupled with a small increase in detectable levels of human papillomavirus deoxyribonucleic acid in cervical samples from patients who had negative results on their previous examination. This study demonstrates a very high level of detectable human papillomavirus deoxyribonucleic acid in exfoliated cervical cells obtained during pregnancy and shows that the detectable levels of human papillomavirus deoxyribonucleic acid fluctuate during pregnancy.     

Mechanism for human papillomavirus transmission at birth

We attempted to investigate mechanisms, in addition to sexual contact, by which human papillomaviruses associated with anogenital tract lesions could be transmitted. Samples of exfoliated cervical cells were obtained from 45 pregnant women and were assayed by Southern blot hybridization analysis for the presence of human papillomavirus nucleic acids. Twenty-five of the 45 women had cells positive for human papillomavirus deoxyribonucleic acid. A neonatal nasopharyngeal aspirate was obtained at term and analyzed for the presence of human papillomavirus deoxyribonucleic acid. We documented the presence of human papillomavirus deoxyribonucleic acid in the oral pharyngeal cavity of the neonates in 15 of 45 nasopharyngeal samples analyzed. Amniotic fluid was obtained from 13 patients when their membranes were artificially ruptured. These samples were assayed for the presence of human papillomavirus deoxyribonucleic acid; two of the 13 amniotic fluid samples contained human papillomavirus deoxyribonucleic acid. The detection of human papillomavirus deoxyribonucleic acid in the oral cavity of neonates is indicative of a perinatal mechanism of viral transmission. The detection of human papillomavirus deoxyribonucleic acid in the amniotic fluid may suggest an in utero mechanism of transmission. However, problems encountered in collecting the amniotic fluid samples preclude us from definitive interpretation of these data.     

21-hydroxylase deficiency and Turner's syndrome: a reason for diminished endometrial receptivity

OBJECTIVE: To report a case of cryptic 21-hydroxylase deficiency identified at the time of ovum donation in a patient with Turner's syndrome. DESIGN: Case report. SETTING: University IVF practice. PATIENT(S): A 28-year-old woman with Turner's syndrome who presented for ovum donation. INTERVENTION(S): Four cycles of donor IVF. MAIN OUTCOME MEASURE(S): Pregnancy, endometrial appearance, progesterone, and 17-hydroxyprogesterone values. RESULT(S): The patient failed two fresh and two frozen ET cycles with donated oocytes. The appearance of the endometrium suggested elevated progesterone before progesterone supplementation. An elevated progesterone was detected but not suppressed by leuprolide acetate. Progesterone was suppressed by adding dexamethasone. The diagnosis of cryptic 21-hydroxylase deficiency was confirmed biochemically. CONCLUSION(S): Patients with Turner's syndrome reportedly have poorer outcomes with donor IVF than other women. They also have an increased incidence of carrying a defective 21-hydroxylase gene. We suggest that some of the poorer outcomes may be explained by the presence of elevated progesterone and recommend evaluation of possible congenital adrenal hyperplasia in patients with Turner's syndrome who want oocyte donation.     

New medical treatments for endometriosis

The medical treatment of endometriosis has long centered upon producing a hypoestrogenic environment by producing pituitary suppression or a progestin-dominant environment. However, as more is uncovered regarding the pathogenesis and pathophysiology of this disease, more targeted therapies can be developed. Current research has focused upon medications designed to attack specific aspects of the development and maintenance of endometriosis. These include progesterone receptor modulators, gonadotropin releasing hormone (GnRH) antagonists, aromatase inhibitors, tumor necrosis factor alpha (TNF-alpha) inhibitors, angiogenesis inhibitors, matrix metalloproteinase inhibitors, pentoxifylline (and other general immune modulators), and estrogen receptor beta agonists. It is hoped that this new wave of medications will improve the response to medical therapy for this disorder.     

Non-surgical management of leiomyoma: impact on fertility

PURPOSE OF REVIEW: This review is designed to discuss the literature, published from December 2002 to January 2004, on the non-surgical treatment of fibroid. All established and new modalities are reviewed, and all new developments in the field are discussed. The resulting impact on the treatment of infertility will also be evaluated. RECENT FINDINGS: In the past year important advances occurred in the medical treatment of uterine fibroids. It was found, in a large randomized trial, that preoperative treatment with gonadotropin-releasing hormone analogue did not improve surgical results or decrease blood loss. However, important strides were made in understanding the molecular biology of the effect of the hormone analogue on fibroids. Other medical therapies investigated include danazol, raloxifene, mifepristone, aromatase inhibitors, and the levonorgestrel-containing intrauterine device. Most promising in terms of long-term usage for reduction of size and symptoms appears to be the combination of gonadotropin-releasing hormone analogue and raloxifene, although selective progesterone receptor modulators may also achieve this aim. However, none avoid producing an anovulatory state that inhibits fertility, and none have been shown to enhance fertility following discontinuation. Uterine artery embolization is another non-surgical technique under intense investigation. The year's literature suggests that while results are comparable with hysterectomy in terms of complication rate and patient satisfaction, there may be important issues for women who wish to undergo the procedure and retain future fertility. Specifically, there is a significant rate of premature ovarian failure, as well as occasional damage to the endometrial vasculature with resulting atrophy and adhesion formation. Improvements in technique, in particular the use of larger and more spherical microspheres for embolization, may reduce these unwanted effects. However, few data exist regarding the course of pregnancy and outcome following embolization. SUMMARY: A number of non-surgical treatments exist for uterine fibroids, but none has been shown to be of value in the patient desiring future fertility. Myomectomy remains the standard of care for such women, and all other therapies should be designated experimental and limited to appropriate investigational studies.     

Circulating leptin levels during ovulation induction: relation to adiposity and ovarian morphology

OBJECTIVE: To assess serum leptin levels based on body habitus and ovarian morphology during controlled ovarian hyperstimulation. Design: Prospective analysis. SETTING: University IVF program. PATIENT(s): Women undergoing IVF-ET were divided into two groups, obese ovulatory women (n = 6; mean (+/-SD) body mass index, 30.1 +/- 0.6 kg/m(2)) and lean ovulatory women (n = 20); mean (+/- SD) body mass index 22.0 +/- 0.2 kg/m(2)). Lean women were categorized further according to whether they had polycystic-appearing ovaries (n = 8) or normal-appearing ovaries (n = 12). INTERVENTION(s): Controlled ovarian hyperstimulation and IVF. MAIN OUTCOME MEASURE(s): Serum estradiol, testosterone, and leptin. RESULT(s): Mean (+/- SD) leptin levels were significantly higher before and after GnRH agonist down-regulation in obese women (41.7 +/- 5.2 pg/mL and 36.1 +/- 5.8 pg/mL, respectively) compared with lean women (8.4 +/- 1.0 pg/mL and 6.9 +/- 1.1 pg/mL, respectively). Mean (+/- SD) leptin levels increased significantly in both groups (54.5 +/- 5.1 pg/mL and 11.7 +/- 1.2 pg/mL, respectively), and the mean (+/-SD) percentage increase was similar (55% +/- 18% and 54.8% +/- 17%, respectively). Mean (+/-SD) leptin levels were similar in women with polycystic-appearing and normal-appearing ovaries before controlled ovarian hyperstimulation, but increased significantly in women with polycystic-appearing ovaries afterward (14.7 +/- 1.8 pg/mL and 9.3 +/- 1.0 pg/mL, respectively). CONCLUSION(s): Significant increases in leptin levels occur during controlled ovarian hyperstimulation, suggesting that leptin plays a role in follicular growth and maturation. The exaggerated response in women with polycystic-appearing ovaries reflects either a greater number of recruited follicles or a predisposition of adipocytes to leptin production.