Treatment of atypical endometrial hyperplasia with an insulin-sensitizing agent.

Endometrial cancer and hyperplasia have long been associated with diabetes. Hyperinsulinemia may have a direct mitogenic effect on the endometrium and may inhibit the effect of progestogen therapy. This case report describes the treatment of a patient with atypical endometrial hyperplasia with an insulin-sensitizing agent. A 37-year-old patient presented after failed treatment of endometrial hyperplasia with progestogen therapy. One month after initiating metformin therapy the patient's endometrial biopsy demonstrated proliferative endometrium. This patient's atypical endometrial hyperplasia regressed after the initiation of treatment with an insulin-sensitizing agent. This relatively new class of drugs may provide an adjunct to the therapy of endometrial hyperplasia.     

Dual suppression with oral contraceptives and gonadotrophin releasing- hormone agonists improves in-vitro fertilization outcome in high responder patients

Certain patients have a tendency for high response to gonadotrophin therapy which is often not ameliorated with prior gonadotrophin- releasing hormone agonist (GnRHa) suppression. As a result, these patients are frequently cancelled and often experience ovarian hyperstimulation syndrome (OHSS) episodes during in-vitro fertilization (IVF)-embryo transfer cycles. Patients with polycystic ovarian syndrome (PCOS) have been noted to be particularly sensitive to exogenous gonadotrophin therapy. We have developed a protocol which is effective in improving IVF outcome in high responder patients, including those with PCOS. Oral contraceptive pills (OCP) are taken for 25 days followed by s.c. leuprolide acetate, 1 mg/day, which is overlapped with the final 5 days of oral contraceptive administration. Low-dose gonadotrophin stimulation is then initiated on the third day of withdrawal bleeding in the form of either human menopausal gonadotrophins or purified urinary follicle-stimulating hormone at a dosage of 150 IU/day. Over a 5 year period, we reviewed our experience utilizing this dual method of suppression in 99 cycles obtained in 73 high responder patients. There were only 13 cancellations prior to embryo transfer (13.1%). The clinical and ongoing pregnancy rates per initiated cycle were 46.5 and 40.4% respectively. Only eight patients experienced mild-moderate OHSS following treatment. For those patients who had undergone previous IVF-embryo transfer cycles at our centre, significant improvements were noted in oocyte fertilization rates, embryo implantation rates and clinical/ongoing pregnancy rates with this protocol. Hormonal analyses revealed that the chief mechanism may be through an improved luteinizing hormone/follicle-stimulating hormone ratio following dual suppression. An additional feature of this dual method of suppression is significantly lower serum androgen concentrations, particularly dehydroepiandrosterone sulphate.      

False-positive Y-microdeletion result for a fertile male caused by an alteration under a PCR primer

The pathogenic relationship between the presence of Y chromosomal microdeletions and male infertility is unclear. Nevertheless, a causal relationship is thought to be probable when loci are shown to be deleted in infertile males but are present in fertile males. Polymerase chain reaction (PCR) analysis of the Y chromosome is now routinely performed in the evaluation of the infertile male, although, until recently, there has been no consensus on how the diagnosis should be performed and which loci or markers should be analysed. The European Academy of Andrology (EAA) published guidelines for the molecular diagnosis of Y chromosomal microdeletions in 1999. Following these guidelines, our laboratory developed assays that incorporated the suggested primer pairs for the recommended Sequence Tagged Sites (STS). A number of fertile (n = 117), infertile (n = 17) and unknown samples (n = 20) were tested in our laboratory as part of the validation to provide a clinical assay. Two multiplex PCR assays were optimized, each of which examined STS markers in the centre of the AZFa, b and c regions of the Y chromosome. We correctly identified all but one of the 154 samples (according to the expected result based on fertility or previous testing at another laboratory). A single equivocal result was observed for a sample obtained from a known fertile male who appeared to be deleted for a single marker, sY84, in the AZFa region but not the adjacent marker, sY86. Follow-up analysis showed that proximal and distal markers within the same region (sY82 and sY98) were also present. Sequencing the region flanking and including the sY84 primer set revealed a single base alteration under the reverse primer, which probably caused the amplification failure. Furthermore, the sY84 sequence itself was present, as was the flanking sequence 50 bp on either side of both primers. This observation underlines the importance of using at least two closely linked STS markers for the reliable diagnosis of Y chromosome microdeletions as proposed by the EAA guidelines.     

Anonymous oocyte donation performed exclusively with embryos cryopreserved at the pronuclear stage

OBJECTIVE: To evaluate the clinical outcomes of patients who participated in an anonymous oocyte donation program that used embryos cryopreserved at the pronuclear stage. DESIGN: Observational study. SETTING: A tertiary care reproductive medicine unit. PATIENT(S): Anonymous oocyte donors and their respective recipients. INTERVENTION(S): Oocyte donors underwent a standard controlled ovarian hyperstimulation protocol and transvaginal ultrasound-guided oocyte retrieval. Oocyte recipients underwent at least one programmed hormone replacement cycle with transcervical ET. MAIN OUTCOME MEASURE(S): Thaw survival, implantation, clinical and ongoing pregnancy rates. RESULT(S): Thirty-six oocyte retrievals resulted in one ET to date. The mean numbers of oocytes that were retrieved and normally fertilized were 18.2 and 11.6, respectively. Fifty-one embryo thaw-transfer cycles were performed, with an embryo thaw survival rate of 93.5%. The clinical and ongoing pregnancy rates per ET were 52.9% and 51%, respectively. The overall implantation rate was 28.7%. The percentage of oocyte retrievals that resulted in at least one ongoing pregnancy to date was 69.4%. CONCLUSION(S): Anonymous oocyte donation can be conducted efficiently with the exclusive use of embryos cryopreserved at the pronuclear stage. This approach facilitates synchronization of the donor-recipient pair, eliminates the risk that recipients will begin hormonal therapy without embryo availability, and produces an acceptable ongoing pregnancy rate per oocyte donation.     

Body mass index and uterine receptivity in the oocyte donation model

OBJECTIVE: To evaluate the relationship of body mass index (BMI) to uterine receptivity under conditions of programmed hormonal support and standardized embryo quality. DESIGN: Retrospective cohort study.A tertiary referral center. PATIENTS: Ninety-seven consecutive first-cycle recipients of anonymous oocyte donation.After programmed hormone replacement, recipients had transfer of embryos derived from oocyte donation. Anonymous oocyte donors received ovarian stimulation and underwent transvaginal ultrasound-guided oocyte retrieval. SETTING: A receiver operator characteristic (ROC) curve of implantation versus BMI.Area under the ROC curve was 0.51, 95% confidence interval (CI) 0.41-0.62, suggesting no relationship between BMI and implantation. There was no difference in implantation rates between obese (BMI >or=30) and nonobese (BMI <30) recipients, odds ratio 1.1, 95% CI 0.5-2.4. CONCLUSION(S): Uterine receptivity was unimpaired in women with increased BMI when hormonal support and embryo quality were standardized.     

Successful elective single blastocyst transfer in a patient with prior repetitive high-order multiple gestations

Multiple gestations remain one of the leading causes of morbidity related to infertility therapy. In the realm of assisted reproductive technologies, multiple gestations can be significantly limited by the reduction in the number of embryos transferred. Significant concern remains that a reduction in the number of embryos transferred may appreciably lower overall chances for pregnancy. Promising new developments are unfolding that may permit improved detection of a single human embryo with high implantation potential. One such development is the use of sequential culture media to allow prolonged culture of embryos to the blastocyst stage. We report a case in which sequential culture and elective transfer of one blastocyst was successfully used in a patient with a profoundly poor obstetrical history because of the complications of high-order multiple gestations.     

Embryo cryopreservation at the pronuclear stage and efficient embryo use optimizes the chance for a liveborn infant from a single oocyte retrieval

OBJECTIVE: To estimate the potential for a liveborn in our program achieved through either fresh or frozen embryos derived from a single oocyte retrieval. DESIGN: Retrospective analysis. SETTING: A tertiary referral reproductive medicine unit. PATIENT(s): All consecutive patients undergoing oocyte retrieval from January 1, 1996, to June 30, 1997. INTERVENTION(s): All couples undergoing IVF-ET at our center are counseled about a specific embryo transfer number after oocyte retrieval based on demographic and historical factors. Only this specified number of embryos is retained in culture. All normally fertilized (2PN) oocytes exceeding this number are immediately cryopreserved at the pronuclear stage. For couples who do not conceive after fresh embryo transfers, frozen embryo transfers are subsequently performed by usually thawing only the number of embryos intended for transfer, thereby conserving remaining embryos for further potential frozen embryo cycles. MAIN OUTCOME MEASURE(s): Liveborn delivery per oocyte retrieval.39.0 years were 61.2%, 59.7%, and 18.5%, respectively. CONCLUSION(s): For women <39 years of age, the efficient use of embryo cryopreservation at the pronuclear stage and economical embryo utilization policies results in cumulative chances for a liveborn exceeding 60%.     

Ovarian hyperstimulation syndrome prevention strategies: oral contraceptive pills-dual gonadotropin-releasing hormone agonist suppression with step-down gonadotropin protocols

The identification of patients at high risk for excessive responses to ovarian stimulation for in vitro fertilization and embryo transfer is essential in the tailoring of safe and effective treatment strategies. Known factors associated with increased sensitivity to gonadotropins include polycystic ovary syndrome, young age, prior ovarian hyperstimulation syndrome (OHSS), high baseline antral follicle count, and high baseline ovarian volume. Although several treatment strategies have been proposed for these patients, this report describes the experience using the dual suppression with gonadotropin step-down protocol. This protocol uses oral contraceptive pretreatment in combination with a long gonadotropin-releasing hormone agonist followed by a programmed step-down in gonadotropin dosing. Hormonal characteristics of dual suppression include an improved luteinizing hormone-to-follicle-stimulating hormone ratio and lower serum androgens, particularly dehydroepiandrosterone sulfate. Clinical characteristics of the protocol include a lower cancellation rate and favorable clinical and ongoing pregnancy rates per initiated cycle while mitigating the risk of OHSS.