Morey Schachter

Intravenous albumin for the prevention of severe ovarian hyperstimulation syndrome in an in vitro fertilization program : a prospective, randomized, placebo-controlled study

OBJECTIVE To evaluate the efficacy of i.v. administration of human albumin solution for the prevention of severe ovarian hyperstimulation syndrome (OHSS). DESIGN A prospective, randomized, placebo-controlled study comparing the effects of i.v. administration of human albumin solution versus sodium chloride 0.9% solution at the time of oocyte retrieval with patients undergoing IVF-ET who are at high risk for the development of severe OHSS. SETTING Specialized assisted reproduction unit. PATIENTS Thirty-one patients undergoing IVF-ET who had serum E2 levels of 1,906 pg/mL (> 7,000 pmol/L) and multiple follicular development on the day of hCG administration. INTERVENTIONS After hCG administration, patients were randomized to receive i.v., either 50 g of human albumin diluted in 500 mL of sodium chloride 0.9% or 500 mL of sodium chloride 0.9% at the time of oocyte retrieval. MAIN OUTCOME MEASURES Ovarian size as measured by pelvic ultrasonography, development of ascites, serum E2 concentrations during the luteal phase, and results of the IVF-ET cycles. RESULTS Although no patient who had received human albumin solution developed severe OHSS, there were four such cases in the control group. All four were hospitalized with marked ascites and ovarian enlargement. There were no significant differences between the two groups comparing serum E2 levels on the day of hCG administration and during the luteal phase, the number of oocytes retrieved, fertilization, and pregnancy rates. CONCLUSIONS Our preliminary results suggest that the administration of human albumin solution may help to prevent the development of severe OHSS in high-risk patients. Further research is needed to assess the potential of this novel approach.

The luteinizing hormone surge—the final stage in ovulation induction: modern aspects of ovulation triggering

OBJECTIVE To compile updated information regarding gonadotropin secretion, specifically the physiology of the midcycle LH surge, in natural cycles and under various ovulation induction protocols. DATA IDENTIFICATION AND SELECTION Studies that deal with the clinical aspects of LH surge manipulation or substitution were identified through literature and Medline searches. RESULTS Three major regulatory factors have been identified as participants in the induction of the midcycle gonadotropin surge. These are hypothalamic GnRH secretion, ovarian and adrenal steroids, and less well-characterized ovarian peptide hormones. Gonadotropin-releasing hormone pulsatility is regulated by a complex mechanism that integrates multiple neurotransmitters and sex steroids. Estradiol plays a central role in the pituitary secretion of LH, which also is influenced by P concentrations. Gonadotropin surge attenuating factor also has been implicated in the regulation of timing and amplitude of the LH surge. Human chorionic gonadotropin is used extensively as a LH surrogate, but its use is associated with a number of disadvantages. Induction of an endogenous LH surge through use of the flare effect of GnRH analogues has been examined more recently and has been found to have several advantages. Recombinant human LH is in the final stages of clinical testing. CONCLUSION Although much is known about the physiology of the midcycle LH surge and its variations under different clinical conditions, new approaches to the induction or substitution of the LH surge currently are being examined and learned. The introduction of recombinant gonadotropins into clinical practice is likely to influence ovulation induction and IVF practice to a significant degree in the near future.

Isolated tubal torsion : clinical and ultrasonographic correlation

A 13 year old girl developed sudden onset of left lower abdominal pain 30 hours prior to arrival. She previously had enjoyed perfect health, and menarche had occurred 3 months before the current episode. Family history was unremarkable, and no history of previous abdominal pain was elicited. After the onset of left abdominal pain, the pain assumed a colicky nature accompanied by nausea and vomiting. No urinary symptoms were encountered, and the patients temperature was normal. On examination, an ill-appearing girl with slight tachycardia of 92 beats per minute was encountered. Tanner pubertal development of grade III was assigned. The abdomen was soft to palpation, and no outright signs of peritoneal irritation were elicited, although some voluntary guarding in the left lower quadrant was noticed. On pelvic examination per rectum, labia and

CLINICAL ASSISTED REPRODUCTION: Improvement of IVF Outcome in Poor Responders by Discontinuation of GnRH Analogue During the Gonadotropin Stimulation Phase—A Function of Improved Embryo Quality

Purpose: To assess the efficacy of a protocol involving the discontinuation of the GnRH analogue at the mid-phase of ovarian stimulation for IVF in patients with a previous poor response.Methods: Prospective case-control evaluation compared with same patients previous performance. Thirty-six patients enrolled in an IVF program were treated in two consecutive cycles. The first with a standardized protocol utilizing mid-luteal administration of Nafarelin (N) 600 mcg/d continued throughout the stimulation phase with human menopausal gonadotropin (hMG) until follicles of 20 mm were identified by transvaginal ultrasound (Standard group). Patients with a poor response in the Standard cycle were treated in the subsequent cycle with N and hMG initially in a similar manner, then N was stopped after 5 days of hMG stimulation (N-stop group). All clinical and laboratory aspects of treatment were done in a similar fashion in both cycles, each patient acting as her own control.Results: Results were analyzed by paired t test. The change in each parameter in the N-stop cycle was expressed as the percent change as compared with the standard protocol cycle for each patient. Peak estradiol (E2) and number of aspirated oocytes were increased in the N-stop cycle (+16.9% and +28%, respectively), but insignificantly so. The percent of cleaving embryos was significantly increased by 27.9% (p = 0.03) in the N-stop cycle, as embryo morphology was improved by 22% (p = 0.02). The efficacy of gonadotropin treatment was enhanced in the N-stop cycle, as expressed by a 32.5% increase in oocytes retrieved per hMG ampoule administered (p = 0.04). Three cycles of 36 were cancelled during the N-stop cycle, whereas only one was cancelled in the standard protocol cycle. Of the 36 patients, 7 conceived in the N-stop protocol and 5 are ongoing pregnancies.Conclusion: Discontinuation of GnRH-a during ovarian stimulation for IVF has a beneficial, but not statistically significant, effect on both E2 and oocyte production. Embryo cleavage rates and morphology were significantly improved, this may be due to improved oocyte quality, which may have been responsible for achieving pregnancies. The efficacy of gonadotropin treatment was enhanced when GnRH-a was discontinued. These results hint that GnRH-a may have a direct negative effect on folliculogenesis and oocytes, which is apparent especially in poor responder patients.

Estrogen biosynthesis--regulation, action, remote effects, and value of monitoring in ovarian stimulation cycles.

OBJECTIVE To review current knowledge regarding estrogen biosynthesis, its regulation and action, specifically concerning local as opposed to remote effects of this hormone, and to examine the effectiveness and prognostic value of monitoring hormone concentrations and endometrial response in cycles of controlled ovarian hyperstimulation. DATA IDENTIFICATION AND SELECTION Studied that relate specifically to estrogen biosynthesis, enzymatic pathways, estrogen receptor physiology, and the clinical aspects of estrogen monitoring were identified through literature and Medline searches. RESULTS Folliculogenesis is the basic unit of ovarian activity, which has a dual purpose: oocyte maturation and steroid production. Steroidogenic granulosa and theca cells cooperate under gonadotropin control to produced estrogens by stimulating synthesis of steroidogenic enzyme messenger RNAs. Steroid synthesis is amplified further by local growth factors and follicular cell multiplication. Estrogen synthesis is directed by FSH, and only small amounts of LH are needed to amplify the follicular estrogenic potential. However, the growth of preovulatory follicles can proceed without LH, under FSH regulation only, even in the presence of low peripheral estrogen levels. Oocyte maturation and fertilization may proceed independently of ambient estrogen levels, leading to the assumption that estrogen exerts a minimal autocrine-paracrine function. The notable effect of follicular estrogen production is to promote adequate receptive endometrium for embryo implantation. Clinical treatment cycles may be monitored more effectively by evaluating end-organ response to estrogen rather than by evaluating absolute serum E2 concentrations or sonographic follicular measurements. CONCLUSION Follicular estrogen production is regulated by a complex set of signals that synergize to produce optimal steroidogenesis. Most importantly, the effect of estrogen is truly an endocrine effect, as it prepares the endometrium for implantation. Therefore, the goal of effective treatment and monitoring strategies should focus on direct assessment of the biologic activity of estrogen as it optimizes endometrial receptivity in anticipation of subsequent implantation.

Successful pregnancy after 24 consecutive fetal losses: lessons learned from surrogacy

OBJECTIVE To offer surrogacy as a treatment option to patients in whom maternal rather than fetal factors are responsible for high-order unexplained habitual abortions. DESIGN Case report. SETTING University hospital. PATIENT(S) A 36-year-old woman with 24 consecutive abortions over 11 years. INTERVENTION(S) A regular IVF procedure in the aborting woman and transfer of two good-quality embryos to the surrogate mother, who had previously received hormones. MAIN OUTCOME MEASURE(S) Ovarian response, oocytes, fertilization, and embryo quality in the aborting patient. Endometrial thickness, implantation, pregnancy, and delivery in the surrogate mother. RESULT(S) Transfer of two embryos to the surrogate mother led to a clinical pregnancy, which was uneventful until term. Cesarean section was performed for breech presentation, with delivery of a healthy male. CONCLUSION(S) Surrogacy can be offered as a treatment option to patients in whom maternal rather than fetal factors are responsible for high-order unexplained habitual abortions.