William N. Burns

Complications associated with the absorption of hysteroscopic fluid media

OBJECTIVES To review the literature concerning complications resulting from absorption of hysteroscopic fluid distension media and to describe methods to treat and prevent these complications. DESIGN All pertinent literature on fluid distension media used for endoscopy, as well as relevant reports concerning the management of fluid and electrolyte imbalance, was reviewed. RESULTS The absorption of large volumes of electrolyte-free, low-viscosity fluid may result in volume overload with water intoxication. Volume overload may cause pulmonary edema, and water intoxication may lead to hyponatremia, hypo-osmolarity, and cerebral edema. In contrast, the absorption of dextran-70 may cause volume overload secondary to the oncotic effect of intravascular dextran. Dextran-70 has been associated with anaphylaxis and coagulation disorders. TREATMENT The use of diuretics is advocated. Urine output must be closely monitored. Judicious correction of electrolyte imbalance will prevent morbidity. PREVENTION Meticulous attention to intraoperative fluid balance is imperative. A multichannel hysteroscope is necessary to keep intrauterine pressure low. Extensive surgical procedures may need to be performed in stages. CONCLUSIONS Severe volume overload and electrolyte imbalance may result from fluid absorption during operative hysteroscopy. Most complications may be avoided by closely monitoring fluid balance intraoperatively.

Elevated serum progesterone levels on the day of human chorionic gonadotropin administration in in vitro fertilization cycles do not adversely affect embryo quality

OBJECTIVE To assess the effect of an elevated serum P level on the day of hCG administration in an IVF cycle on resulting embryos by evaluating their performance at subsequent frozen ET. DESIGN A retrospective study. PARTICIPANTS Ninety-six consecutive patients undergoing frozen ET cycles were studied in a tertiary care center. MAIN OUTCOME MEASURES Serum obtained on the day of hCG administration in an IVF cycle was assayed for E2 and P by RIA. The main outcome measured was the development of a clinical pregnancy in a subsequent frozen ET cycle. RESULTS Using a previously described breakpoint in serum P concentration of 0.9 ng/mL (2.86 nmol/L), 8 of 69 (11.6%) frozen ETs in which embryos from low P level IVF cycles were transferred and 7 of 27 (25.9%) frozen ETs of embryos from elevated P level IVF cycles were transferred resulted in the development of clinical pregnancies. Although this does not clearly demonstrate superiority of embryos obtained from elevated P cycles, employing a power calculation, the probability that the pregnancy rate in the elevated serum P group is at least equal to the observed rate in the low P group is 92.8%. CONCLUSION These data suggest that an elevated serum P level on the day of hCG administration does not adversely affect the quality of oocytes or resulting embryos.

A prospective, randomized trial comparing two different intrauterine insemination regimens in controlled ovarian hyperstimulation cycles *

OBJECTIVE To compare a single periovulatory intrauterine insemination (IUI) with a regimen employing two IUIs, one before ovulation and one after ovulation, in patients undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins (hMG) combined with human chorionic gonadotropin (hCG). DESIGN A randomized, prospective trial. PARTICIPANTS Thirty-one consecutive patients undergoing 49 cycles of controlled ovarian hyperstimulation/IUI were studied in a tertiary care setting. MAIN OUTCOME MEASURES Ovulation was determined sonographically. The establishment of a clinical pregnancy was defined by either ultrasonographic verification of cardiac activity within an intrauterine fetus, or histologic confirmation of trophoblast in a surgical specimen. RESULTS Clinical pregnancies developed in 2 of 23 cycles in the single insemination group, compared with 12 of the 23 cycles in the double insemination group. Cycle fecundity was significantly higher for group II (0.522) than for group I (0.087) patients (P = 0.003). CONCLUSION In hMG/hCG cycles, two IUIs timed as described above are superior to one periovulatory insemination.

Survival of cryopreservation and thawing with all blastomeres intact identifies multicell embryos with superior frozen embryo transfer outcome

OBJECTIVE To assess the impact of survival of cryopreservation and thawing with all blastomeres intact on the outcome of multicell frozen ET. DESIGN Retrospective study. SETTING Academic assisted reproductive technology program. PATIENT(S) One hundred sixteen exclusively multicell frozen ETs in 78 patients. INTERVENTION(S) Frozen ET. MAIN OUTCOME MEASURE(S) Relation of embryonic blastomere survival to the outcome of frozen ET (i.e., pregnancy). RESULT(S) When at least one embryo survived with all blastomeres intact, the total pregnancy rate (biochemical, clinical, or delivered) was 37.7%, the clinical pregnancy rate was 24.6%, and the delivered pregnancy rate was 18.8%. When no embryo survived with all blastomeres intact, the corresponding rates were 10.6%, 8.5%, and 6.4%. The differences in the total pregnancy rate and the clinical pregnancy rate were statistically significant. The delivered pregnancy rates approached statistical significance. CONCLUSION(S) Multicell embryonic survival of cryopreservation and thawing with all blastomeres intact identifies embryos with superior developmental potential.

Endometriosis and Infertility: Is There a Cause and Effect Relationship?

An association between endometriosis and infertility has long been noted. Endometriosis affects approximately 5% of the general population. In infertile women, the prevalence may be as high as 30%. Multiple studies, the majority of which are retrospective, indicate that the monthly fecundity of patients with endometriosis may be decreased by half compared to women without the disease. The precise cause-effect relationship between endometriosis and infertility remains controversial. In advanced cases of endometriosis, with distorted pelvic anatomy, the mechanism of infertility is more easily explained. Recent evidence suggests that treatment of early-stage endometriosis may increase pregnancy rates. Many etiologies of infertility in early-stage endometriosis have been proposed. These include endocrine dysfunctions such as luteal phase defect and luteinized unruptured follicle syndrome. In the last 15 years, alterations in the local pelvic immune environment have been the subject of multiple basic science investigations. Unfortunately, there is no satisfactory hypothesis that unequivocally explains the association of early stages of endometriosis with infertility.

Follicular size at the time of human chorionic gonadotropin administration predicts ovulation outcome in human menopausal gonadotropin-stimulated cycles

OBJECTIVE The objectives of this study were: (1) to correlate follicle size by transvaginal sonography with ovulation outcome in cycles of controlled ovarian hyperstimulation with human menopausal gonadotropins; (2) to determine if follicular size on the day of human chorionic gonadotropin (hCG) administration predicts the incidence of ovulation; and, if so, (3) to derive a mathematical model that predicts the number of expected ovulations in any given cycle of controlled ovarian hyperstimulation. DESIGN A retrospective analysis. PARTICIPANTS Forty-nine consecutive patients undergoing 122 cycles of controlled ovarian hyperstimulation were studied in a tertiary care setting. MAIN OUTCOME MEASURES Follicular size and evidence of ovulation were determined sonographically. The main outcome measure was the rate of ovulation per follicle size. RESULTS The percentages of follicles measuring less than or equal to 14 mm, 15 to 16 mm, 17 to 18 mm, 19 to 20 mm, and greater than 20 mm on the day of hCG administration that subsequently ovulated were 0.5%, 37.4%, 72.5%, 81.2%, and 95.5%, respectively. CONCLUSIONS (1) Follicular size on the day of hCG administration correlates with the incidence of ovulation. (2) The expected number of ovulations in any given controlled ovarian hyperstimulation cycle can be predicted with 95% confidence using the accompanying equation.

Serum progesterone concentrations on the day after human chorionic gonadotropin administration and progesterone/oocyte ratios predict in vitro fertilization/embryo transfer outcome.

PurposeIn gonadotropin-releasing hormone analogue-pretreated in vitro fertilization-embryo transfer cycles, pregnancy rates are inversely related to serum progesterone levels on the day of administration of human chorionic gonadotropin. The relationship of the progesterone concentration on other days in the periovulatory period to pregnancy rates in such cycles is little studied. We therefore retrospectively analyzed the relationship between progesterone concentrations on the day after human chorionic gonadotropin and pregnancy in 114 cycles, 28 and 23 of which produced clinical and ongoing/delivered pregnancies, respectively. To assess the effect of the extent of follicular luteinization on success, we also studied the relationship between the progesterone concentration per oocyte retrieved and pregnancy for the day of and day after human chorionic gonadotropin.ResultsProgesterone concentrations on the day after human chorionic gonadotropin were inversely associated with clinical pregnancy by multiple logistic regression analysis (P<0.05). Progesterone/oocyte ratios were inversely associated with clinical pregnancy (P<0.05) and ongoing/delivered pregnancy (P<0.02) for both the day of and the day after human chorionic gonadotropin.ConclusionThe study results extend the window of time during which elevated progesterone concentration is associated with poor outcome to at least 2 days. This finding is consistent with hypothetical mechanisms attributing the link between progesterone concentration and outcome to either endometrial or follicle/oocyte events. The association of lack of follicular luteinization (low progesterone per oocyte ratios) and favorable outcome suggests a predominant effect of progesterone on follicle/oocyte quality. Further studies are needed to clarify the mechanisms underlying the association between progesterone and in vitro fertilization-embryo transfer outcome.

Is there a risk of cytomegalovirus transmission during in vitro fertilization with donated oocytes

OBJECTIVE To define the risk of human cytomegalovirus (HCMV) transmission from donated oocytes. DESIGN Prospective study. SETTING University IVF program. PATIENT(S) Sixty-seven couples undergoing 72 cycles of IVF-ET. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Serum from both partners (women: n = 71; men: n = 60) was obtained for detection of antibodies to HCMV. Semen before preparation (n = 53), sperm after preparation (Percoll gradient; n = 47), cervical mucus aspirated at the time of oocyte aspiration (n = 70), and uninseminated oocytes and embryos not suitable for cryopreservation (n = 568) were frozen in liquid nitrogen. Polymerase chain reaction was used for detection of HCMV (immediate early 1 gene) in all samples collected. RESULT(S) Serum antibodies to HCMV were found in 62% of the women and 37% of the men tested. Human cytomegalovirus DNA was detected in 25% of the ejaculates and in 19% of the cervical mucus samples. There was no amplification of HCMV DNA from oocytes or embryos. CONCLUSION(S) Because we were unable to amplify HCMV DNA from any of the oocytes or embryos, it seems unlikely that HCMV is transmissible through oocyte or embryo donation.

Diminished α-inhibin messenger ribonucleic acid in in vitro fertilization-embryo transfer poor responders reflects declining follicle reserve *

OBJECTIVES To quantitate and compare granulosa cell alpha-inhibin messenger RNA (mRNA) levels in IVF-ET poor and good responders and thereby learn how alpha-inhibin mRNA levels change in states of diminished ovarian responsiveness. DESIGN Ribonucleic acid analysis of stored luteinized granulosa cell samples. SETTING Academic tertiary care institution. PATIENTS Fifty-three women undergoing follicle aspiration for IVF-ET were studied. Patients were classified as poor responders (n = 16) or good responders (n = 37) according to their E2 concentration on the day of hCG; the E2 of poor responders was < 1,000 pg/mL (3,671 pmol/L) and that of good responders was > or = 1,000 pg/mL (3,671 pmol/L). MAIN OUTCOME MEASURES Messenger RNA levels were measured using dot blot RNA analysis. The following parameters were determined or derived: total mRNA levels, total alpha-inhibin mRNA levels, alpha-inhibin mRNA per follicle, and proportional alpha-inhibin mRNA as the ratio of alpha-inhibin mRNA:total mRNA. RESULTS Proportional alpha-inhibin mRNA and alpha-inhibin mRNA per follicle were not significantly different between poor responders and good responders. Total mRNA and total alpha-inhibin mRNA levels, however, were diminished significantly in poor responders. CONCLUSIONS The observations that proportional alpha-inhibin mRNA and alpha-inhibin mRNA per follicle do not significantly change in poor responders, whereas total alpha-inhibin mRNA does, indicate that the decrease in total alpha-inhibin mRNA in poor responders reflects a decreased pool of total mRNA, likely because of a reduction in follicle number. These findings are in contrast to other recent reports that describe a change in granulosa cell function accompanying states of decreased ovarian responsiveness.

Expression of the human inhibin α-subunit gene in preovulatory granulosa-theca cells

Inhibin, a gonadal peptide that suppresses pituitary follicle-stimulating hormone, with lesser or no effect on luteinizing hormone, has recently been purified and the complementary deoxyribonucleic acid sequences cloned. Inhibin contains two subunits, labeled a-subunit and (3-subunit. Here we report for the first time the detection of human inhibin a-subunit gene expression in preovulatory granulosa-theca cells by Northern analysis. The transcript is the same size as previously reported for human placenta and corpus luteum, suggesting that the same gene is being expressed in all three tissues. These findings are consistent with previously reported Southern analysis of deoxyribonucleic acid, which showed only one copy of the a-inhibin gene in the human genome. Thus current data strongly suggest that there is only one copy of the inhibin a-subunit gene in the human genome, and this same gene is expressed in granulosa-theca cells, corpus luteum, and placenta. (AM J OBSTET GYNECOL 1990;162:273-7.)