Correlation between sonographic follow-up of follicular growth, serum and salivary estradiol in women undergoing controlled ovarian stimulation (IVF/ICSI).

AIM OF THE STUDY: Investigation of the correlation between serum estradiol (E2), salivary E2 and sonographic measurements of follicles in women undergoing controlled ovarian stimulation (COS) for IVF/ICSI. METHODS: This is a prospective study performed at the Department of Reproductive Medicine of Ghent University Hospital (Belgium) between November 2016 and January 2017 over a total of 40 patients. During routine COS, two-dimensional measurements of the follicles were performed using transvaginal ultrasound (TVUS) and E2 was measured in saliva and serum. A linear Mixed-Effects model (MIXED) was built, using SPSS Statistics 24. RESULTS: Statistical analysis shows a strong linear correlation between serum and salivary E2. For every single unit increase in serum E2 (+ 1 ng/L) the estimated saliva E2 concentration is expected to increase with 0.011 pg/mL (95% CI [0.009 - 0.01]). Strong linear correlations between both saliva and serum E2 and follicular dimensions were also found. For every millimetre increase in follicle diameter the estimated serum E2 concentration is expected to increase with 8.32 ng/L (95% CI [7, 10-9, 54]). For every millimetre increase in follicle diameter the estimated saliva level of E2 is expected to increase with 0.11 pg/mL (95% CI [0.09 - 0.13]). CONCLUSIONS: A strong correlation between serum and salivary E2 concentrations was found. In addition, both are strongly correlated with the product of the number of follicles and their average diameter, measured by TVUS. More investigation needs to be done to find out if salivary E2 is an effective tool for monitoring IVF cycles.

Gender bias in the disposition of frozen embryos.

OBJECTIVE: To examine the gender differences found among couples when choosing the disposition of their frozen embryos. DESIGN: Retrospective chart review. SETTING: University affiliated in vitro fertilization (IVF) center. PATIENTS: Couples undergoing their first cycle of assisted reproductive technology (ART). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Choice of disposition of gametes and embryos. RESULT(S): Gender bias is found when couples choose the disposition of their frozen embryos, but not when they choose the disposition of their gametes. CONCLUSION(S): Gender bias was found in couples who made decisions regarding the disposition of their frozen embryos.

To blastocyst or not to blastocyst? That is the question.

Recent advances in culture media preparations have allowed for cleavage embryos to be developed to the blastocyst stage. Blastocysts are regarded as having increased implantation potential, and two blastocysts are typically transferred, which reduces the occurrence of high order multiple gestations. However, with current techniques, most cleavage embryos do not become blastocysts and it is not clear how many of these embryos would have implanted had they been replaced at the cleavage stage. Furthermore, experience with blastocyst cryopreservation is lacking and the overall benefit of blastocyst culture is unknown, unless we consider the combined pregnancy rates of both fresh and frozen blastocysts.

Multivariate analysis of factors predictive of successful live births in in vitro fertilization (IVF) suggests strategies to improve IVF outcome.

PURPOSE: Our purpose was (1) to identify characteristics correlated with pregnancy outcome, (2) to use these characteristics to predict in vitro fertilization (IVF) outcome, and (3) to develop strategies that might improve IVF success. METHODS: Maternal age, cause for IVF, donor insemination, rank of attempt, serum estradiol and luteinizing hormone levels on the day of human chorionic gonadotropin administration, flexible vs rigid catheter, number of embryos transferred of each morphologic type, and cell number were analyzed by logistic regression. RESULTS: Variables positively correlated with success are as follows: (1) for pregnancy, endometriosis and 2-, 3-, and 4-cell good and 4-cell excellent embryos; (2) for live births, 2-, 3-, and 4-cell good and 4-cell excellent embryos and donor insemination; and (3) for multiple births, 2- and 4-cell good and 4-cell excellent embryos. Maternal age was negatively correlated with live births. CONCLUSIONS: Embryos derived from IVF have different potentials for implantation, live births, and multiple births. Transferring one additional good-quality embryo for each 5 years of incremental increase in maternal age is predicated to improve live birth rates without increasing multiple births.

Sperm morphology and in vitro fertilization outcome: a direct comparison of World Health Organization and strict criteria methodologies.

OBJECTIVE: To perform a direct comparison of two sperm morphology methodologies with regard to IVF outcome. DESIGN: Blinded comparison of two methods of morphology assessment using the same morphology slides. PATIENTS: Data were obtained from 132 couples in a consecutive series of patients undergoing IVF. MAIN OUTCOME MEASURES: Two practical end points were selected for analysis for each couple: the presence of any fertilization and the number of fertilized eggs. Normal traditional morphology was defined as > or = 40% normal forms in a sample and normal strict criteria was defined as > or = 4%. RESULTS: Traditional morphology demonstrated a higher sensitivity and negative predictive value than strict criteria (87% versus 61%, and 68% versus 36%, respectively). Positive predictive value and specificity were also numerically greater but did not reach statistical significance. Abnormal traditional morphology, but not strict criteria, was associated with reduced fertilization even among samples with normal sperm concentration and motility. Samples with normal morphology were associated with a greater number of fertilized eggs per couple than those with abnormal morphology: this difference was 3.2 fertilized eggs for traditional morphology and 1.6 for strict criteria. Overall, for samples with < 40% by traditional morphology only one case yielded more than two fertilized eggs. In contrast, up to five fertilized eggs were noted for the lowest strict criteria scores. CONCLUSIONS: Comparison of traditional morphology and strict criteria with regard to IVF outcome favored traditional morphology in several areas. In particular, low scores were more predictive of poor IVF outcome.

Success rates with gamete intrafallopian transfer and in vitro fertilization in women of advanced maternal age.

OBJECTIVE: To evaluate the effect of maternal age on outcomes for IVF and GIFT in women 40 to 45 years of age. DESIGN: Retrospective. SETTING: Boston IVF, a free-standing university-affiliated IVF and GIFT unit. PATIENTS: A total of 2,931 cycles of IVF and 1,826 cycles of GIFT were analyzed in women undergoing assisted reproductive technologies (IVF or GIFT) using autologous eggs. INTERVENTIONS: Medical records of patient outcomes were reviewed. RESULTS: For patients undergoing IVF, the cancellation rate for initiated cycles showed significant differences in women aged 25 to 39 (38.3%), women aged 40 to 43 (49.5%), and women aged 44 to 45 years (69.5%). A significantly lower delivery rate per stimulation and delivery rate per retrieval was found in women aged 40 to 43 years when compared with women aged 25 to 39 years. No deliveries occurred in 59 cycles in women aged 44 to 45 years, thereby representing a significant difference when compared with both women aged 25 to 39 years and women aged 40 to 43 years. For patients undergoing GIFT, the cancellation rate for initiated cycles was significantly higher in women aged 40 to 43 (25.0%) and 44 to 45 years (31.0%) when compared with women aged 25 to 39 years (15.1%). A significantly lower delivery rate per stimulation and delivery rate per retrieval was found in women aged 40 to 43 and 44 to 45 years when compared with women aged 25 to 39 years. CONCLUSIONS: Success rates for IVF and GIFT decline significantly in women > 40 years old. Women aged > or = 44 years are unlikely to benefit from the use of IVF and GIFT.

Gonadotropin-releasing hormone antagonist versus agonist administration in women undergoing controlled ovarian hyperstimulation: cycle performance and in vitro steroidogenesis of granulosa-lutein cells.

OBJECTIVES: We sought to determine the effectiveness of a gonadotropin-releasing hormone antagonist compared with an agonist in suppressing a spontaneous luteinizing hormone surge in women undergoing controlled ovarian hyperstimulation for in vitro fertilization and gamete intrafallopian transfer and to examine whether in vivo administration of these analogs effects granulosa-lutein cells steroidogenesis in vitro. STUDY DESIGN: This prospective case-control study included 30 healthy women undergoing ovarian hyperstimulation with human menopausal gonadotropins. Fifteen women received the Nal-Glu antagonist, 5 mg intramuscularly daily, when the lead follicle was > or = 15 mm or serum estradiol level was > or = 500 pg/ml. The control group included 15 women who underwent oocyte retrieval on the same day as the study subjects and were given the agonist leuprolide acetate, 250 micrograms subcutaneously daily, starting on cycle day 1. Granulosa-lutein cells were purified from follicular aspirates from six subjects and six controls and cultured in parallel, evaluating basal progesterone production, progesterone response to follicle-stimulating hormone or luteinizing hormone and aromatase activity. RESULTS: No difference was demonstrated in the total amount of gonadotropins received by the two groups. Overall, the gonadotropin-releasing hormone antagonist was given for only 2.5 +/- 0.2 (mean +/- SEM) days before human chorionic gonadotropin administration. The antagonist group showed significantly lower levels of serum luteinizing hormone than did the agonist group, 1.0 +/- 0.2 versus 4.2 +/- 0.5 mIU/ml (p = 0.0001) on the day of human chorionic gonadotropin administration. Serum estradiol levels were significantly lower in the antagonist than the agonist group, 820 +/- 120 versus 1361 +/- 110 pg/ml (p = 0.003) on the day of human chorionic gonadotropin administration. There was no difference in the number of retrieved oocytes, but the antagonist group had a higher proportion of mature oocytes, 82% +/- 4% versus 62.4% (p = 0.02), and a higher proportion of embryos of good quality, 69.8% +/- 9.8% versus 44.3% +/- 7.2% (p = 0.03) in the agonist group. Granulosa-lutein cells from antagonist-treated women showed significantly lower aromatase activity the first 6 hours after retrieval, 17.6 +/- 1.6 versus 31.3 +/- 7.4 ng/ml per 6 hours estradiol (p = 0.03), whereas basal and gonadotropin-stimulated with progesterone responses were similar. CONCLUSION: Gonadotropin-releasing hormone antagonist administration during the late follicular phase resulted in lower serum luteinizing hormone and estradiol levels and more mature oocytes and embryos of better quality compared with gonadotropin-releasing hormone agonist administration. These results suggest that gonadotropin-releasing hormone antagonist administration in ovarian hyperstimulation has practical advantages over the agonist regimen. Gonadotropin-releasing hormone analogs may have direct action on ovarian function with differential effects on granulosa-lutein cell aromatase activity. This could explain the lower serum estradiol levels routinely observed in women given gonadotropin-releasing hormone antagonist.

Relationship between urinary estrone conjugates as measured by enzyme immunoassay and serum estradiol in women receiving gonadotropins for in vitro fertilization.

OBJECTIVE: Our purpose was to determine whether urinary estrone conjugates (E1C) as measured by enzyme immunoassay correlate with serum estradiol (E2) in women undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins. DESIGN: This was a prospective, clinical study. SETTING: The study took place in an outpatient, university-affiliated in vitro fertilization (IVF) unit. INTERVENTIONS: First morning urine samples were analyzed for E1C using a competitive solid-phase microtiter enzyme immunoassay and the value was corrected for urinary creatinine (E1C/Cr). The value was compared to morning serum E2 as determined by radioimmunoassay. RESULTS: Mean E2 and E1C/Cr levels demonstrated a similar pattern on the days before hCG administration. The correlation between E1C and E2 was 0.85 (P < 0.0001). Furthermore, the correlation between the number of follicles greater than 12 mm was as high for E1C/Cr (rho = 0.71, P < 0.001) as it was for E2 (rho = 0.74, P < 0.0001). CONCLUSIONS: Urinary E1C/Cr levels in women receiving hMG correlate with serum E2. Further studies are necessary to determine whether E1C is clinically useful to predict ovarian hyperstimulation syndrome.

Fertility and the use of assisted reproductive techniques in the adult male exstrophy/epispadias patient.

These three cases exemplify, in increasing order of complexity, how the common sense application of already successful techniques might be applied to augment the chance of pregnancy in this group of patients. We believe this to be the first report specifically outlining measures that may assist this group in their goal of pregnancy achievement. To our knowledge, vasal sperm aspiration has never been used for this indication.

Comparison of pregnancy rates following gamete intrafallopian transfer (GIFT) under general anesthesia with thiopental sodium or propofol.

STUDY OBJECTIVE: To determine whether the pregnancy rate for gamete intrafallopian transfer (GIFT) patients who received thiopental sodium was different from the pregnancy rate for patients who received propofol for the induction of general anesthesia. DESIGN: Retrospective review of clinical records. SETTING: Private outpatient infertility clinic. PATIENTS: Two hundred eighty-two consecutive GIFT procedures performed on 230 patients with infertility. INTERVENTION: Patients undergoing GIFT were divided into two groups on the basis of whether they received thiopental or propofol for induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: Clinical pregnancy following each GIFT procedure was assessed by multiple-serum beta human chorionic gonadotropin and ultrasound determinations. The pregnancy rates of 24.6% and 25.8% for the thiopental and propofol groups, respectively, were not significantly different. CONCLUSIONS: The pregnancy rate following GIFT for patients given propofol for induction of general anesthesia did not differ from that for patients given thiopental.

Laparoscopic salpingectomy using conventional laparoscopy equipment.

Laparoscopic surgery has gained wide acceptance in the treatment of ectopic pregnancy. When compared with conventional surgical techniques, the laparoscopic approach reduces perioperative morbidity, hospital costs, length of hospital stay, and recovery time. Laparoscopic surgery, however, often requires special surgical skills and expensive equipment. In this paper we review the literature on the efficacy of the laparoscopic approach to salpingectomy and report a simple technique for such a procedure. Any gynecologist who performs laparoscopic tubal sterilization by electrocautery has the necessary equipment and can develop the skills to carry out this procedure.

Comparison of unilateral and bilateral tubal transfer in gamete intrafallopian transfer (GIFT).

Gamete intrafallopian transfer (GIFT) is traditionally performed by delivering gametes into the ampullary region of either one or two fallopian tubes. The choice is made by the surgeon at the time of laparoscopy based upon the patient's anatomy, the number of oocytes available, and clinical judgment. In this nonrandomized, retrospective review, 399 tubal gamete transfers were performed over a period of 18 months, 133 to a single tube and 266 to both tubes. A clinical pregnancy rate of approximately 24% was observed in each modality. The multiple pregnancy rate of 31.3% for one tube was not significantly different from the 25% seen for two tubes. Unilateral tubal transfer offers the distinct advantages of less gamete and tissue handling. This, along with the apparent same outcome parameters, makes unilateral tubal transfer the preferred method of returning gametes at GIFT.

Gamete intrafallopian transfer: assessment of the optimal number of oocytes to transfer.

The optimum number of oocytes that should be transferred at the time of gamete intrafallopian transfer (GIFT) is important information. Nonessential oocytes can be inseminated and frozen for later use or the extra oocytes can be donated to another women. In this preliminary study, the results of 399 consecutive GIFT procedures were evaluated retrospectively as a function of the number of oocytes transferred. Women who received four or more oocytes were three times more likely to achieve a clinical pregnancy than those who received three or less. There was no statistically significant difference in pregnancy rates between patients who received five, six, seven, or eight oocytes. Oocytes in excess of five may be more effectively used if they are fertilized and frozen as embryos for later transfer rather than replacing them all at the time of GIFT.

Successful use of gamete intrafallopian transfer does not reverse the decline in fertility in women over 40 years of age.

To assess the impact of assisted reproductive technologies on the potential fertility of older women, we report our experience with gamete intrafallopian transfer (GIFT) in a large number of women 40 years of age and older. One hundred twenty-two GIFT cycles were initiated in 59 women over 18 months. Seventy-three tubal transfers were performed, resulting in seven clinical pregnancies, a rate of 9.6% per transfer. This contrasts with a 27.3% clinical pregnancy rate per transfer in women under 40. Thus, older patients require thorough counseling regarding the decreased likelihood of success despite the use of assisted reproductive technologies.

Pregnancy after gamete intrafallopian transfer in a woman with primary infertility and in utero exposure to diethylstilbestrol. A case report.

In utero exposure to diethylstilbestrol (DES) has an adverse effect on reproductive performance and may be associated with infertility. Gamete intrafallopian transfer (GIFT) is a new reproductive technique that has been advocated as an alternative to in vitro fertilization in women with at least one normally functioning fallopian tube. The process involves the translaparoscopic placement of oocytes and sperm into the fallopian tube. The technique has been successful in treating infertility due to endometriosis, male factors and immunologic factors as well as unexplained infertility. We accomplished the first successful GIFT procedure in a woman with significant uterine effects from prenatal DES exposure. This technique may prove to be an effective treatment for infertile women with DES exposure who have no adequate explanation for their infertility.

Comparison of follicular fluid hormones in patients with one or two ovaries participating in a program of in vitro fertilization.

The authors recently reported on the follicular response to clomiphene citrate (CC) and human menopausal gonadotropins (hMG) in patients with one or two ovaries participating in a program of in vitro fertilization. This study was designed to analyze the follicular fluid hormones in patients with one or two ovaries in order to elucidate the compensatory mechanisms by which a single ovary achieves folliculogenesis equal to that of two ovaries. Twenty-one follicles from ten patients with one ovary were compared to 30 follicles from eight patients with two ovaries present. Ovulation induction was achieved using a standard protocol with sequential CC and hMG. Human chorionic gonadotropin (hCG) was administered after appropriate estradiol (E2) values and ultrasonic findings, and oocyte aspiration by laparoscopy was performed 33 hours later. Follicular fluid (FF) hormones were assayed by standard radioimmunoassay techniques and no differences were found in the levels of progesterone (P), testosterone, estradiol/testosterone ratio, prolactin, follicle-stimulating hormone, and luteinizing hormone. However, follicles from patients with one ovary had a lower mean concentration of E2 (286 versus 542 ng/ml, P = 0.001) and a lower mean E2/P ratio (0.055 versus 0.107, P = 0.016). Also, the mean follicular diameters and volumes were similar in both groups. In view of the authors' previous finding of a comparable number of mature oocytes from patients with either one or two ovaries, these data suggest that follicles from patients with a single ovary may achieve comparable oocyte maturity despite less efficient production of E2. Although FF E2 levels were lower in patients with one ovary, this dysynchrony between oocyte maturity and FF E2 values does not appear to affect outcome adversely.

Elevated serum dehydroepiandrosterone sulfate levels in patients with insulin resistance, hirsutism, and acanthosis nigricans.

The association of insulin resistance, hyperandrogenism, and acanthosis nigricans is well established. The ovary is thought to be the site of the excess androgen production. The purpose of this study was to assess the adrenal contribution to the hyperandrogenic state in these women. Twenty-three patients presenting with the combination of hyperinsulinemia, elevated testosterone (T) levels, and acanthosis nigricans were investigated for the source of the increased androgen production. Twelve patients had elevated serum dehydroepiandrosterone sulfate (DS) levels (high DS group) suggestive of increased adrenal androgen production. Eleven patients had normal DS levels (normal DS group). Both normal DS and high DS groups had similar basal serum insulin levels and similar insulin response curves after a 3-hour, 75-gm, oral glucose tolerance test. No correlation was found between serum T or DS levels and either basal serum insulin levels or the area under the insulin response curve. These data suggest that DS levels are frequently elevated in patients with hirsutism, acanthosis, and hyperinsulinemia. Furthermore, the lack of association between serum DS and serum insulin levels suggests that insulin does not directly affect adrenal androgen production, or vice versa.

Premature ovarian failure. Current concepts.

Premature ovarian failure is not uncommon. It can occur at any age and has important implications for both patient and clinician. Various therapeutic options are available, including in vitro fertilization with donor oocytes.