A comparison of the use of clomiphene citrate and letrozole in patients undergoing IVF with the objective of producing only one or two embryos.

AIM: The objective of this study was to compare the use of clomiphene citrate and letrozole in an IVF setting in which the objective was to produce only one or two embryos. Either clomiphene citrate or letrozole was used in conjunction with gonadotropins without the use of GnRH antagonists. METHODS: Sixty-two patients received either clomiphene citrate or letrozole with low dose gonadotropins in 128 non-randomized treatment cycles. HCG was given when one follicle was at least 17 mm. Oocyte retrieval was done 34 hours later and fertilization was performed using ICSI. RESULTS: There were no statistically significant differences in the number of large follicles produced, oocytes fertilized, endometrial thickness, clinical pregnancy rates, or delivery rates in patients taking letrozole compared to clomiphene citrate. More mature oocytes were retrieved after clomiphene citrate, but a subset analysis of patients undergoing both treatments did not support this difference. The only statistically different finding in both analyses was the peak estradiol levels during treatment, which averaged 516 pg/ml with letrozole and 797 pg/ml with clomiphene citrate (p = 0.005). Overall, the cancellation rate due to a premature LH surge was 5%. An average of 2.8 mature oocytes were recovered, 2.1 oocytes fertilized and 1.6 embryos were transferred. The overall clinical pregnancy rate per transfer was 25% (95% confidence interval 17.7% to 33.3%) and the overall live birth rate per transfer was 19.2% (95% confidence interval of 11.6% to 26.8%). CONCLUSIONS: Other than peak estradiol levels, there were no clinically significant differences when letrozole or clomiphene citrate was used for mild ovarian stimulation for IVF. There were only rare cancellations because of premature LH surges.

The potential of letrozole use for priming in vitro maturation cycles.

OBJECTIVE: To compare the pregnancy rates with two different methods of priming for in vitro maturation cycles (IVM). Cycles using letrozole together with hCG were compared to cycles using FSH together with hCG in 75 cycles in patients being treated for infertility by IVM. STUDY DESIGN: Retrospective cohort non-inferiority trial Results: Using letrozole for priming was found to not be inferior to using FSH for priming cycles. The live birth rate per transfer was 31.6% in letrozole primed cycles compared to 20.8% in FSH primed cycles (not significant). However, FSH priming produced more oocytes that were mature on the day of retrieval (p = 0.004) and also resulted in more high quality embryos than did letrozole priming (p = 0.004). CONCLUSION: Letrozole may be used for priming in IVM cycles in which the clinician views the characteristics of letrozole as more desirable than FSH.

Approaches to oocyte retrieval for advanced reproductive technology cycles planning to utilize in vitro maturation: a review of the many choices to be made.

PURPOSE: To evaluate the minutiae associated with oocyte retrieval for use in human in vitro maturation IVF cycles. Many of the relevant features of oocyte retrieval were identified by the Trounson group in the first publication on successful in vitro maturation using transvaginal oocyte harvesting and these were a major focus of this review. METHODS: Published human and animal studies, together with topics from mathematics and mechanics, were used to try to understand the importance of different choices that could be made in structuring a transvaginal oocyte retrieval procedure in humans. RESULTS: The published literature suggests that the highest oocyte recovery rate occurs using higher pressures and thicker needles, but this comes at the cost of damaging the cumulus oocyte complex. It is likely that this damage is caused by the sheer stress forces exerted on the cumulus oocyte complex due to parabolic forces associated with laminar flow within the needle and is likely worsened by irregular forces during intervals of turbulent flow occurring with entry into the needle. Larger needles also cause more pain and may be associated with more blood loss. Higher velocity entry into the follicle, needle rotation to prevent premature blockage of the lumen, and carefully timed applications of aspiration pressure theoretically optimize oocyte retrieval technique. CONCLUSIONS: Oocyte retrieval for in vitro maturation is effected by the interaction of the many choices that need to be made in planning for the procedure. The most difficult decision involves aspiration pressure or fluid flow rate and needle size.

A comparison of the Cook single lumen immature ovum IVM needle to the Steiner-Tan pseudo double lumen flushing needle for oocyte retrieval for IVM.

PURPOSE: This study compared the impact of using the Steiner-Tan pseudo double lumen needle for antral follicle oocyte retrieval to using a conventional non-flushing needle. The Steiner-Tan needle has a much smaller dead space than the needles commonly used for IVM oocyte retrievals. METHODS: This was a retrospective cohort study. The patient population was determined by the time period in which a patient underwent IVM in a single physician's IVF practice. The following data was abstracted from clinical and embryology records: oocytes retrieved, oocytes matured, early maturing oocytes, oocytes fertilized, embryo quality measures, retrieval time, needle punctures, clot formation, and clinical pregnancy rate. RESULTS: The Steiner-Tan needle did not increase the number of oocytes retrieved. It also did not increase the time required for retrieval. However, flushing of antral follicles significantly decreased clot formation in fluid aspirates. Use of the Steiner-Tan needle also significantly decreased the number of vaginal needle punctures during each case. There was a trend toward improved embryo quality, but statistical power was inadequate to show a difference. CONCLUSIONS: The primary benefit of the Steiner-Tan needle was on the embryological aspects of IVM. Decreased blood and blood clots in the aspirates made an IVM retrieval more like conventional IVF for the embryologist. The patient also experienced less tissue trauma without increasing anesthesia or surgical time. There was no improvement in the number of oocytes retrieved, but based on the results, we hypothesized that oocytes were more commonly retrieved from slightly large follicles than when using a routine needle.

Polar body fragmentation in IVM oocytes is associated with impaired fertilization and embryo development.

PURPOSE: The significance of finding a fragmented first polar body in an oocyte prepared for ICSI is controversial with most recent publications suggesting that it is not prognostic for oocyte fertilization or embryo development. Our purpose was to look at this question in the context of oocytes not stimulated for conventional IVF. METHODS: Oocytes obtained for IVM and obtained from follicles at most 12 mm in diameter were evaluated for their polar body morphology soon after they entered metaphase II when they were denuded in preparation for ICSI. Records were evaluated retrospectively for the fertilization rate and the embryo growth rate (cell number) on each day of development for embryos with normal appearing polar bodies or fragmented polar bodies, but no other cytoplasmic dysmorphisms. RESULTS: Oocytes with fragmented polar bodies were significantly less likely to fertilize than oocytes with normal appearing polar bodies (p < 0.0001). Embryos which developed from oocytes with fragmented polar bodies had significantly impaired growth compared to embryos that developed from oocytes with normal appearing polar bodies (p = 0.0328). CONCLUSIONS: Fragmented polar bodies likely reflect cytoplasmic incompetence.

Ovarian drilling in infertile women with polycystic ovary syndrome.

Ovarian drilling is a laparoscopic treatment for polycystic ovary syndrome. As with wedge resection, it is unclear why women with this syndrome ovulate after the procedure. Studies describing the clinical response of over 600 patients to this treatment have appeared in the medical literature. Attention to detailed steps can guide experienced laparoscopic surgeons to apply this technique to appropriate patients who are experiencing infertility due to polycystic ovary disease.

Pregnancy in women under 35 with elevated early follicular phase follicle-stimulating hormone levels. A report of five cases.

BACKGROUND: An elevated follicle-stimulating hormone (FSH) level in the early follicular phase in women over age 40 has been associated with decreased potential for achieving pregnancy utilizing in vitro fertilization (IVF). Also, pregnancies achieved by such women commonly result in miscarriage. CASES: A private infertility practice surveyed all patient records in women under age 35 who were undergoing either IVF or controlled ovarian hyperstimulation. Five women were identified with persistent early follicular phase elevation of FSH. Patients were reviewed in terms of ovulatory function and other fertility characteristics. Four of these patients achieved pregnancy and delivered normal infants. CONCLUSION: Women under age 35 with elevated early follicular phase FSH levels constitute a heterogeneous group of patients. An elevated FSH level in such women may not have the same prognosis as it does in women over age 40.

Laparoscopic management of polycystic ovarian disease.

Laparoscopic treatment of polycystic ovary syndrome has its roots in bilateral wedge resection. Although it is still unclear why surgery is effective in treating this syndrome, more than 600 cases of patients treated laparoscopically have been reported in the literature. Recent publications enhance our understanding of appropriate patient selection as well as the effectiveness of, and the complications associated with, this procedure.

Use of a single intrauterine insemination of defrosted cryopreserved sperm for therapeutic donor insemination.

OBJECTIVE: To evaluate the efficacy of a protocol employing defrosted cryopreserved sperm as a single well-timed intrauterine insemination. DESIGN: A retrospective observational study. SETTING: A university fertility service and a private fertility practice located in small metropolitan areas. PARTICIPANTS: All 138 donor sperm recipients (348 cycles) treated on this protocol by the author during a 27 month period were evaluated. All 86 patients (200 cycles) treated using intracervical inseminations bracketing the time of ovulation during the same time period were also evaluated. RESULTS: A single well-timed intrauterine insemination had an associated pregnancy rate of 13.8% per cycle. In contrast, intracervical inseminations bracketing the time of ovulation had an associated pregnancy rate of 5% per cycle (P < .005). CONCLUSIONS: A single well-timed intrauterine insemination of defrosted cryopreserved sperm is more efficacious and less expensive than intracervical inseminations bracketing the time of ovulation.

Sperm motility, morphology, hyperactivation, and ionophore-induced acrosome reactions after overnight incubation with mycoplasmas.

OBJECTIVE: To evaluate the effect on the function on human sperm of overnight incubation with mycoplasma species. DESIGN: Prospective controlled in vitro study. SETTING: Community-based sperm bank and andrology laboratory. INTERVENTIONS: Percoll-separated sperm were incubated overnight with a low densities of Myco-plasma hominis and Ureaplasma urealyticum serotypes. MAIN OUTCOME MEASURES: Motility, midpiece and tail morphology, hyperactivation after overnight capacitation, and acrosome status after incubation with calcium ionophore. RESULTS: Overnight incubation with mycoplasma species resulted in small but highly statistically significant differences in motility, morphology, hyperactivation after overnight capacitation, and proportion acrosome reacted after incubation with calcium ionophore compared with controls. CONCLUSIONS: Incubation with mycoplasma species impairs sperm physiology. Identification and treatment of mycoplasma may augment a physiology-based infertility evaluation.

A conservative, low-cost superovulation regimen.

The protocol reported decreases the cost and inconvenience of inducing the growth of multiple ovulatory follicles in selected infertility patients. Safety was maintained by treating patients with relatively small amounts of exogenous gonadotropins and using patient response to slowly increase gonadotropin stimulation in subsequent cycles. The pregnancy rate was 26% per cycle. For couples with male factor infertility, it was 20% per cycle. This regimen may be especially suitable for the practitioner with only a few patients requiring this therapy who may not have the capacity to obtain daily estradiol levels.

Abdominal instillation of high-molecular-weight dextran or lactated Ringer's solution after laparoscopic surgery. A randomized comparison of the effect on weight change.

Abdominal fluid retention after the instillation of lactated Ringer's solution into the abdomen after operative laparoscopy was evaluated by comparing the serial weights of patients receiving lactated Ringer's after surgery to those of patients treated with the abdominal instillation of high-molecular-weight dextran and to those of negative controls. Twenty-four patients were randomized to receive either lactated Ringer's or high-molecular-weight dextran after operative laparoscopy. Patients undergoing only diagnostic laparoscopy served as negative controls. Patients receiving either lactated Ringer's or high-molecular-weight dextran had increased weights as compared to the negative controls for at least 36 hours (P less than .5), although the weight gain in the treatment groups did not differ statistically significantly. The weight gain remained significantly greater than in the negative controls on postoperative days 3 and 4 in patients treated with dextran. Since the "flotation" effect of dextran in preventing pelvic adhesions is likely to be most pronounced in the immediate postoperative period, the findings suggest the need for a reinterpretation of adhesion prevention studies in which the use of dextran was compared to that of lactated Ringer's solution or to saline as a negative control.

Macromastia in a woman treated with penicillamine and oral contraceptives. A case report.

A patient with Wilson's disease treated with penicillamine developed severe hirsutism. After treatment with oral contraceptives, her breasts enlarged rapidly, and she experienced cyclic mastodynia. Around the time of her breast enlargement she also developed gingival hyperplasia.

The effect of human follicular fluid on endothelial cells: proliferation and DNA synthesis.

Human follicular fluid has been reported to cause angiogenesis. Although endothelial cell mitogenesis is a major component of the process of angiogenesis, the findings in the literature regarding the effects of human follicular fluid in in vitro endothelial cell growth assays are equivocal. In the present study, we examined the effect of human follicular fluid from preovulatory follicles on fetal bovine aortic endothelial cell proliferation. Human serum was used as a control since follicular fluid is largely a transudate of serum and could contain serum-derived endothelial cell mitogens. Neither human follicular fluid nor serum directly caused endothelial cell proliferation. However, follicular fluid, as well as serum, caused an increase in thymidine incorporation by endothelial cells, and resulted in an increased proportion of cells in the DNA synthesis and G2 phases of the cell cycle. Although follicular fluid was not directly mitogenic, it, in contrast to human serum, together with fetal bovine serum markedly enhanced endothelial cell proliferation beyond that caused by fetal bovine serum alone. These results suggest that a combination of factors, some of ovarian origin present in follicular fluid, and others from as yet unidentified sources, govern the mitogenic component of new blood vessel growth in the ovary.

Abbreviated tables for estimating fetal weight with ultrasound.

Tables containing 23 entries for estimating fetal weight with ultrasound parameters have proven to be equivalent to the longer tables in current use.

Multiple simultaneous predictors of gestational age. An application of Bayes' theorem.

Most obstetricians share the belief that an estimate of gestational age based on several clinical measures that agree with one another is more accurate than an estimate based on a single measurement. This paper presents a formal justification for this belief by applying Bayes' theorem to calculate the probability of a fetus being a certain gestational age by using information from several clinically established single predictors. The application of Bayes' theorem justifies the use of multiple measures of gestational age in individual ultrasound examinations and the use of serial ultrasound studies in the third trimester to more accurately estimate gestational age. The same technique could be applied to obstetric research studies that need to establish accurate gestational dating.

Steroid profiles of follicular fluids from a patient with the empty follicle syndrome.

Steroid profiles of follicular fluid obtained from a patient during a cycle in which no oocytes were recovered in 12 follicular aspirates were compared with those of fluid obtained both from cycles of the same patient and from cycles of other patients when oocytes were recovered. Follicles aspirated in the cycle when no oocytes were recovered were shown to be neither atretic follicles, follicular cysts, nor prematurely luteinized follicles. The steroid profile of follicular fluid from the index cycle was characterized by a markedly increased estradiol-to-progesterone ratio and an increased androstenedione level. This, together with a comparison to the steroid profiles of fluid from follicles containing either fertilizable or nonfertilizable oocytes, suggests that the empty follicle syndrome may reflect a dysfunctional ovulation induction.

Major congenital anomalies in infants and glycosylated hemoglobin levels in insulin-requiring diabetic mothers.

Glycosylated hemoglobin levels were obtained in 133 diabetic pregnancies. Nongestational diabetic mothers delivered of infants with major congenital anomalies had significantly higher glycosylated hemoglobin levels than the remaining nongestational diabetic mothers (P less than .001). The higher a mother's glycosylated hemoglobin level, the higher her risk of having a severely affected infant was. The positive predictive value for a nongestational diabetic mother having an infant with severe congenital anomalies was 26% if the glycosylated hemoglobin level was greater than or equal to 11%, 40% if the level was greater than or equal to 12%, and 56% if the level greater than or equal to 13%. However, high glycosylated hemoglobin levels in insulin-requiring gestational diabetic mothers were not predictive of major congenital anomalies.