Frozen-thawed embryo transfer and live birth: Long-term follow-up after one oocyte retrieval.

Frozen-thawed embryos accounted for 39% (249 of 639) of live births from 931 consecutive first oocyte retrievals after median follow-up of 6.5 years with consistent use of pronuclear-stage freezing and cleavage-stage transfer. Survival after thaw was 95% (2,129 of 2,247). Implantation and live birth rates per individual frozen-thawed embryo transfered were 22% (431 of 1,937) and 18% (346 of 1,937), respectively.

Diagnosis of polycystic ovaries by three-dimensional transvaginal ultrasound.

OBJECTIVE: To study diagnostic thresholds for polycystic ovary (PCO). DESIGN: Retrospective cohort study. SETTING: Academic hospital. PATIENT(S): Normoandrogenic ovulatory women and patients with polycystic ovary syndrome (PCOS). INTERVENTION(S): Two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasound. MAIN OUTCOME MEASURE(S): The mean follicle number per ovary (FNPO) of both ovaries and the maximum number follicles in a single sonographic plane (FSSP) of either ovary were determined using 3D transvaginal ultrasound. Ovarian volume was determined using 2D transvaginal ultrasound. RESULT(S): Twenty-nine normoandrogenic ovulatory women were compared with 10 patients with PCOS. Diagnostic thresholds for PCO with 100% specificity as determined by receiver operator characteristic (ROC) curves were > or =20 for mean FNPO, > or =10 for maximum FSSP, and > or =13 cm3 for ovarian volume. Both 2D and 3D transvaginal ultrasound were highly accurate in the diagnosis of PCO as determined by areas under the curve (AUC) that were >90% for all three measures. CONCLUSION(S): Mean FNPO and maximum FSSP by 3D transvaginal ultrasound have comparable high accuracy for diagnosis of PCO. The diagnostic threshold with 100% specificity for mean FNPO is > or =20, which is greater than suggested by the Rotterdam Consensus Workshop in 2003. Use of the consensus standard, consequently, may result in overdiagnosis of PCO. A threshold of > or =20 mean FNPO using 3D transvaginal ultrasound may be appropriate to minimize false-positive diagnoses of PCO.

Polycystic ovaries and ovarian hyperstimulation syndrome: a systematic review*.

OBJECTIVES: To assess and quantify the relationship between polycystic ovaries (PCOs) and ovarian hyperstimulation syndrome (OHSS). DATA SOURCES: Published studies, any language, identified through MEDLINE, EMBASE, BIOSIS, Web of Science, and bibliographies. Studies were selected if exposure (ultrasound findings of PCO before treatment) and outcome (OHSS) could be abstracted to two-by-two tables. RESULTS: Ten studies, meeting inclusion and exclusion criteria, were analyzed. When PCO were present, the combined odds ratio for OHSS was 6.8 (95% confidence interval 4.9-9.6). CONCLUSION: There is a significant and consistent relationship between PCO and OHSS. When PCO are present before treatment with assisted reproduction, deliberate policies to moderate treatment appear justified.

Cryosystem assessment by glucose uptake of murine blastocysts.

Glucose uptake was used as a measure of metabolic activity and implantation potential to compare vitrification and slow freezing in a prospective randomized trial using murine blastocysts. Frozen 2-cell embryos (n = 132) thawed and cultured for 48 h to the blastocyst stage were randomly divided into four groups: (i) control - not refrozen; (ii) slow freezing using a programmed rate (PR); (iii) vitrification by super-cooled (VSC) liquid nitrogen; and (iv) vitrification in liquid nitrogen (VLN). Upon re-thawing, embryos were cultured individually for 24 h to determine glucose uptake non-invasively. Morphological assessments included total cell counts and inner cell mass (ICM) detection following immunosurgery. Mean glucose uptake was lower for each treatment (PR and VSC, 4.3 pmol/embryo per h; VLN, 4.9 pmol/embryo per h) versus controls (6.8 pmol/embryo per h). PR and VSC embryos had fewer cells (57.4 +/- 24.2 and 64.1 +/- 31.5) versus controls (85.7 +/- 26.2), and fewer embryos containing a detectable ICM (42.9 and 61.8%) compared with controls (88.2%). The only difference between control and VLN embryos was absolute glucose uptake, although in both treatments glucose uptake was increased from embryos with an ICM compared with those without. Glucose uptake appears to be a sensitive, non-invasive method to validate cryopreservation protocols.

Insulin and messenger ribonucleic acid expression of insulin receptor isoforms in ovarian follicles from nonhirsute ovulatory women and polycystic ovary syndrome patients.

Insulin action is mediated by two insulin receptor (IR) isoforms, differing in mitogenic and metabolic function. IR isoform expression might occur in human granulosa cells and could be altered in polycystic ovary syndrome (PCOS) from hyperinsulinemia. To determine the relationship between granulosa cell IR isoform expression and follicular fluid insulin concentration in individual follicles, 18 normal women and seven PCOS patients receiving gonadotropins for in vitro fertilization were studied. Glucose tolerance testing was performed before pituitary desensitization, and fasting serum insulin was measured at oocyte retrieval. Granulosa cells and fluid aspirated from the first follicle were used to determine IR isoform mRNA expression and insulin concentration, respectively. IR isoform A mRNA expression was greater than that of IR isoform B expression in normal mural granulosa and cumulus cells, without a cell type effect. Intrafollicular insulin levels increased with adiposity and serum insulin levels at oocyte-retrieval but did not predict IR mRNA expression. Total IR mRNA expression, but not intrafollicular insulin levels, was elevated in PCOS patients, whereas intrafollicular insulin levels were increased in women with impaired glucose tolerance. Granulosa cell IR heterogeneity, together with adiposity-dependent intrafollicular insulin availability, introduces a novel mechanism by which insulin may affect granulosa cell function within the follicle.

Vitrification versus programmable rate freezing of late stage murine embryos: a randomized comparison prior to application in clinical IVF.

A prospective randomized trial was performed to compare post-thaw development of murine blastocysts following programmable rate freezing and two methods of vitrification. Frozen 2-cell murine embryos (n = 429) thawed and cultured for 48 h, were randomly allocated by stage of development into four groups: control (not refrozen), programmable rate freezing (PR) in 0.25 ml straws, vitrification in flexible micropipettes by immersion in super-cooled (VSC) liquid nitrogen (LN2), and vitrification in flexible micropipettes by immersion in LN2 (VLN). Survival, developmental stage progression, presence or absence of an inner cell mass (ICM), and cell counts were recorded 24 h post-thaw. All measured outcomes were different between embryos from the control group and all freezing methods. Controlled-rate freezing resulted in the lowest total cell counts and fewest embryos with a distinct ICM. A higher percentage of embryos survived 24 h post-thaw, progressed to more advanced developmental stages and had higher total cell counts after VLN compared with PR. Moreover, fewer embryos, frozen by either PR or VSC, contained a detectable ICM compared with VLN. These data demonstrate that vitrification may be a better method for freezing murine blastocysts than PR, and may prove to be a superior method for freezing human blastocysts.

Lidocaine vaginal gel versus lidocaine paracervical block for analgesia during oocyte retrieval.

BACKGROUND: Evidence from randomized trials suggests that pain relief during oocyte retrieval is superior when adjunctive paracervical block is used in addition to sedation alone. Vaginal application of lidocaine gel is a non-invasive alternative to lidocaine paracervical block. The goal of the present trial was to compare analgesia with lidocaine vaginal gel versus lidocaine paracervical block. METHODS: A parallel-group randomized trial of adjunctive lidocaine vaginal gel versus adjunctive lidocaine paracervical block (with sedation for both groups) was performed in participants undergoing oocyte retrieval. Measured outcomes were subjective pain experiences. Subjects provided self-reported ratings of pain and anxiety. Visual analogue scales were used to measure pain during different procedural stages. The McGill Pain Questionnaire was used to measure pain character and the total pain experience. RESULTS: During application of lidocaine, pain ratings were less for vaginal gel than paracervical block. In contrast, during insertion of the aspiration needle and aspiration of follicles, pain ratings were greater for lidocaine vaginal gel. Total pain experience was greater with lidocaine vaginal gel. CONCLUSIONS: Subjective measures of pain intensity and the total pain experience were greater with lidocaine vaginal gel compared with lidocaine paracervical block.

Cumulative first live birth after elective cryopreservation of all embryos due to ovarian hyperresponsiveness.

OBJECTIVE: To estimate cumulative chance for first live birth after elective pronuclear stage cryopreservation of all embryos due to ovarian hyperresponsiveness. DESIGN: Retrospective analysis with longitudinal follow-up. SETTING: Academic hospital. PATIENT(S): Thirty subjects with elective cryopreservation of all embryos due to ovarian hyperresponsiveness. INTERVENTION(S): Elective cryopreservation of all embryos at the pronuclear stage (n = 30) and subsequent cryopreserved-thawed ET (n = 51). MAIN OUTCOME MEASURE(S): Cumulative chance for first live birth. RESULT(S): Cumulative chance for first live birth was 77% when analyzed by intention to treat and 82% by treatment with ET. Nearly 40% of live births were multiple. CONCLUSION(S): Cumulative first live birth increased with repetitive ET after elective pronuclear stage cryopreservation of all embryos due to ovarian hyperresponsiveness. Multiple births, however, were frequent. In the context of initial ET attempts in young women, transfer of no more than two cryopreserved-thawed embryos is advised.

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.

Embryo donation: attitudes toward donation procedures and factors predicting willingness to donate.

BACKGROUND: The aim of the study was to assess infertile couples' attitudes toward the procedures of embryo donation (ED) and to identify factors predicting interest in donation. METHODS: Fifty-one couples who had received IVF treatment and had subsequently had embryos cryopreserved for >3 years were located and sent written information about the procedures for ED and possible implications of donation. A total of 49 couples agreed to participate in the study with 36 women and 31 men subsequently returning questionnaires describing their reasons for not claiming unused embryos and attitudes towards ED. RESULTS: Patients were supportive of donor screening procedures, but less comfortable sharing non-identifying information. Comfort levels declined as information became increasingly personal. Support for unconditional (i.e. the donation of embryos without conditions attached) and conditional (i.e. where couples could limit the donation of their embryos to persons/couples according to their preferences) models of donation was highly polarized and a substantial minority expressed strong opposition to each model. Willingness to donate was associated with greater comfort about disclosing personal information, a desire to know the outcome of donation and willingness to have future contact with a child, but not with current family size. CONCLUSIONS: Comfort in sharing information with a recipient couple is more important than acceptance of screening procedures, or attainment of family size goals in predicting willingness to donate embryos. Offering the option of conditional donation could increase the acceptability of ED for some patients.

SOGC clinical practice guidelines. Hirsutism: evaluation and treatment.

OBJECTIVES: To review the etiology, evaluation, and treatment of hirsutism. EVALUATION: A thorough history and physical examination plus selected laboratory evaluations will confirm the diagnosis and direct treatment. TREATMENT: Pharmacologic interventions can suppress ovarian or adrenal androgen production and block androgen receptors in the hair follicle. Hair removal methods and lifestyle modifications may improve or hasten the therapeutic response. OUTCOMES: At least six to nine months of therapy are required to produce improvement in hirsutism. EVIDENCE: The quality of evidence reported in this guideline has been determined using the criteria described by the Canadian Task Force on the Periodic Health Examination. RECOMMENDATIONS: Hirsutism can be slowly but dramatically improved with a three-pronged approach to treatment: mechanical hair removal, suppression of androgen production, and androgen receptor blockade. Lifestyle changes including weight loss and exercise will lower serum androgen levels and improve self-esteem. The patient should be educated regarding associated health problems or long-term medical consequences of hyperandrogenism, including obesity, irregular menses, anovulation, infertility, pregnancy-induced hypertension, diabetes, hyperlipidemia, hypertension, and heart disease.

Success of intrauterine insemination in women aged 40-42 years.

OBJECTIVE: To determine how advancing female age decreases successful outcomes of intrauterine insemination (IUI) alone or combined with ovarian stimulation. DESIGN: Retrospective review. SETTING: Academic fertility center. PATIENT(S): Infertile men and women. INTERVENTION(S): Intrauterine insemination alone or combined with ovarian stimulation. MAIN OUTCOME MEASURE(S): Pregnancy rates, miscarriage rates, and live birth rates per insemination cycle according to female age. RESULT(S): The 1,117 cycles of IUI resulted in 217 pregnancies, for an overall pregnancy rate for all female ages of 19.4% and a live birth rate of 12.9% per cycle inseminated. The overall live birth rate per insemination declined with advancing maternal age. CONCLUSION(S): Advancing female age decreases successful outcomes with IUI. The live birth rate with IUI for women 40-42 years old (n = 82) was 9.8% per insemination and may demonstrate that IUI is an appropriate treatment for this age group of women.

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.