Analysis of Implantation in Assisted Reproduction Through the Use of Serial Human Chorionic Gonadotropin Measurements

Purpose: Our purpose was to examine implantation of singleton pregnancies achieved following various assisted reproductive technologies (ARTs) through the appearance and rising titers of serum human chorionic gonadotropin (hCG) levels. Methods: A total of 114 singleton pregnancies resulting from in vitro fertilization and intrauterine insemination was analyzed. Patients were divided into five groups according to the type of ovarian stimulation protocol [gonadotropin stimulation with/without the use of gonadotropin-releasing hormone agonist (GnRHa), long protocol, or flare-up technique] and to the day of embryo transfer (day 2 or day 3 after oocyte retrieval). Serial serum hCG levels were measured between 10 and 25 days after fertilization and log-transformed. Linear regression analyses were performed and extrapolated to hCG = 10 mIU/ml (hCG ₁₀ ), which was used as an estimate of detectable implantation. The slopes of the regression lines were used to estimate the rising speed of hCG. Results: There were no significant differences in the days of hCG in maternal serum to reach 10 mIU/ml (implantation) or in the slopes of the regression lines for all five studied groups. Conclusions: The appearance of hCG in maternal serum was used to assess the time of clinically detectable implantation. Furthermore, because hCG production is a marker of trophoblastic activity, its serum doubling time was used as an indicator of embryo quality. Results showed that in various ART protocols with and without GnRHa, there were no significant differences in implantation time or embryo quality. Embryo development in early pregnancy follows a preprogrammed-timing schedule and depends mainly on the embryonic age of the health, successfully implanted conceptus.     

Intra-articular methylprednisolone acetate injection at the knee joint and the hypothalamic–pituitary–adrenal axis: a randomized controlled study

The objective of this study was to evaluate the effect of intra-articular corticosteroid injection (IACI) of methylprednisolone acetate (MPA) on the hypothalamic–pituitary–adrenal (HPA) axis in patients with osteoarthritis of the knee. Patients with symptomatic osteoarthritis of the knee who failed to respond to nonsteroidal anti-inflammatory medications and physical therapy were randomized between group 1 and group 2. Group 1 patients had an IACI of 80 mg of MPA at the knee joint and group 2 patients had an intra-articular injection (IAI) of 6 ml (60 mg) of sodium hyaluronate (control group). Immediately prior to the IAI and on weeks 1, 2, 3, 4, and 8 following IAI, patients from both groups underwent a low-dose (1 μg) adrenocorticotropin hormone (ACTH) stimulation test. Demographic, clinical, laboratory, and radiologic variables were documented in all patients. Both criteria of <7 μg/dl increase in the serum cortisol level and absolute levels of <18 μg/dl 30 min following the ACTH stimulation test were used to define secondary adrenal insufficiency (SAI). Twenty patients were randomized in each group. In group 1, 25 % of patients had SAI vs. none in group 2 (p?=?0.0471). The earliest SAI was observed at week 2, and latest SAI was observed at week 4. SAI was observed at one time point, two consecutive time points, or two separate time points in the same patient. There was no correlation between SAI and any of the demographic, clinical, or laboratory variables. An IACI of 80 mg MPA at the knee joint induced a transient SAI in 25 % of the patients, an effect that was observed between week 2 and week 4 following the IACI.     

Ovarian stimulation for in vitro fertilization in low-responder patients using pulsatile intravenous follicle stimulating hormone

There is a subset of patients who fail to respond adequately to exogenous gonadotropin stimulation for in vitro fertilization (IVF). In this study, six such low-responder patients who had inadequate stimulations with high-dose intramuscular (im) follicle stimulating hormone (FSH) were treated in a subsequent cycle with pulsatile intravenous (iv) FSH. A paired analysis was performed to compare the cycles using high-dose im FSH with those using pulsatile iv FSH. Trough serum FSH levels were significantly higher with pulsatile iv FSH. No significant difference was noted in the stimulation characteristics or the number or quality of oocytes retrieved and embryos transferred. No pregnancies occurred in either group. While pulsatile iv administration of gonadotropin increases serum FSH levels, it does not appear to have a major impact on follicular stimulation or outcome in low-responder patients undergoing IVF.     

In vitro fertilization and embryo transfer (IVF/ET): An established and successful therapy for endometriosis

The purpose of this report is to present a 6-year experience in the management of endometriosis with in vitro fertilization and embryo transfer (IVF/ET). We divided 136 patients who underwent 280 cycles into three groups: (1) previous history of endometriosis but normal pelvis at the time of oocyte retrieval, (2) stages I–II endometriosis (revised AFS classification), and (3) stages III–IV endometriosis. The stimulation protocols, estradiol (E₂) responses, and distribution of terminal E₂ patterns were similar in all groups. Group 3 had significantly fewer preovulatory and immature oocytes retrieved and fewer embryos transferred. The fertilization rate and the per cycle/per transfer pregnancy rates were similar in all groups. The miscarriage rate was higher in group 3, and the on-going pregnancy rate per cycle was lower, Luteal phase E₂ and progesterone levels were comparable in all groups. No differences were found when groups 2 and 3 were analyzed for the presence of one or two ovaries or the presencelabsence of ovarian endometriosis. The overall fertilization rate, the per cycle/per transfer pregnancy rates, and the miscarriage rate were similar to those of tubal factor patients. We underscore the excellent out-come of patients with minimal or mild endometriosis in IVF/ET. We conclude that patients with moderate or severe endometriosis have a compromised reproductive potential, probably because of a reduced oocyte recovery rate and poor embryo quality.     

Is the Timing of Implantation Affected by Zona Pellucida Micromanipulation?

Purpose: Our purpose was to examine the timing ofimplantation and early embryo development following uterinetransfer of oocytes/embryos previously subjected to zonapellucida micromanipulation. Methods: A total of 68 singleton pregnancies resulting fromIVF and embryo transfer with/without micromanipulation.Patients were divided into four groups according to the typeof micromanipulation technique: assisted hatching, embryobiopsy, intracytoplasmic sperm injection, and nomicromanipulation (control group). Serial serum -hCG levels weremeasured between 10 and 25 days after fertilization andlog-transformed. Linear regression analyses were performedand extrapolated to hCG = 10 mIU/ml (hCG₁₀) to estimatedetectable implantation. The slopes of the regression lineswere used to estimate the rising speed of hCG, an indirectsign of embryo development. Results: There were no significant differences among groupswith respect to hCG₁₀, the slopes or intercepts of theregression lines. Conclusions: Various oocyte/embryo microsurgicalprocedures used in ART involving zona pellucida manipulationdo not appear to affect the timing of implantation or earlyembryo development.     

A prospective randomized comparison of single- and double-lumen needles for transvaginal follicular aspiration

Patients undergoing ultrasound-directed transvaginal follicular aspiration in a large in vitro fertilization (IVF) program were randomized for retrieval with either a single-lumen needle (SLN;N=22) or a double-lumen needle (DLN;N=22) to compare recovery rates and the technical aspects of their use. Two hundred ten and two hundred two follicles were aspirated with each needle, respectively. Follicular diameters were measured ultrasonically at the time of aspiration and recorded. One or more washes were performed when using the DLN and the SLN was withdrawn each time to recover the fluid in the dead space of the needle. The distribution of follicular sizes was the same for both needles. Oocyte recovery rates (SLN=65.7%; DLN=63.9%) and the incidence of fractured zonae (SLN=9.1%; DLN=6.4%) were the same for both needles (>0.50; <0.01). Although there were no differences between the two needles in the number of oocytes provided for IVF, there were technical differences. The DLN needle was more flexible and frequently deviated from the projected path as observed by ultrasound. The SLN may be preferable because it is technically easier to use; however, there may remain specific indications for the use of the DLN.     

Pycnodysostosis. Orthopedic aspects with a description of 14 new cases.

Pycnodysostosis is an uncommon form of osteosclerosing bone disease. The orthopedic aspects are illustrated by 14 new cases.     

The prevalence of human immunodeficiency virus in patients and their spouses entering a large in vitro fertilization program

Between September 1987 and August 1989, all patients and their spouses entering our in vitro fertilization (IVF) program were screened for the human immunodeficiency virus (HIV) using the enzyme-linked immunosorbent assay (ELISA). Of 848 patients and 848 spouses tested, all but 4 patients and 1 husband tested negative. Of those who tested positive on repeat testing with ELISA, only one was positive on Western blotting (HIV prevalence, 0.59 per 1000). During this same time period 1187 samples of human cord blood were used to make tissue culture medium for the IVF embryology laboratory. One sample was discarded because of positive HIV on ELISA and Western blotting; two other samples were discarded because of positivity to the hepatitis B surface antigen. While we believe that routine HIV screening of IVF patients and their spouses is indicated, this population is of low risk for HIV positivity. Furthermore, continued screening of human sera used to make tissue culture media for IVF is mandatory.Presented at the 45th Annual Meeting of the American Fertility Society, November 11–16, 1989, San Francisco, California.