Probability of live birth after IVF/ICSI treatments in female early onset cancer survivors: a Finnish population-based registry study.

STUDY QUESTION: Does the probability of a live birth after fresh IVF/ICSI cycles with autologous oocytes differ in early onset female cancer survivors compared to their siblings? SUMMARY ANSWER: The probability of a live birth was similar in female cancer survivors and siblings after four fresh IVF/ICSI cycles. WHAT IS KNOWN ALREADY: Fertility preservation strategies are rapidly being developed to help female cancer patients who wish to have children later. However, there are only a few studies available on fertility treatments and following live births in female cancer survivors before fertility preservation strategies became available. In one of them, the probability of a live birth was reduced after assisted reproductive technology with autologous oocytes in cancer survivors compared to siblings. STUDY DESIGN, SIZE, DURATION: In this retrospective, register-based study, data from Finnish registers on cancer, birth and prescribed medications were merged to identify 8944 female cancer survivors (diagnosed with cancer between 1953 and 2012 at the age of 0-40 years) and 9848 female siblings of survivors eligible for IVF/ICSI treatments between January 1993 and December 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fresh IVF/ICSI cycles and following live birth rates (LBRs) within 22-48 weeks in cancer survivors and siblings at the age of 20-41 years were identified. A binomial regression model with log-link function was used to calculate risk ratio (RR) for live births after fresh IVF/ICSI cycles in survivors compared to siblings, adjusting for attained age and calendar time. A Poisson regression model was used to estimate incidence rate ratios (IRRs) for an IVF/ICSI treatment, as well as overall live births, including both pregnancies after fertility treatments and spontaneous pregnancies, in survivors compared to siblings. MAIN RESULTS AND THE ROLE OF CHANCE: We observed an overall decreased LBR, irrespective of IVF/ICSI treatments, in cancer survivors compared to siblings (IRR 0.68, 95% CI 0.64-0.71). All in all, 179 (2.0%) survivors and 230 (2.3%) siblings were prescribed fertility drugs for IVF/ICSI treatments (IRR 0.72, 95% CI 0.62-0.84). For the first fresh IVF/ICSI cycle, the LBR was 17.2% among survivors and 15.7% among siblings (RR 1.13, 95% CI 0.72-1.87). The mean LBR after four fresh IVF/ICSI cycles was not statistically different in survivors compared to siblings. LIMITATIONS, REASONS FOR CAUTION: In this study, only IVF/ICSI treatments with autologous oocytes were included. The probability of a live birth after a frozen embryo transfer or oocyte donation could not be evaluated in this study. Information on miscarriages, extrauterine pregnancies or termination of pregnancies was not available. WIDER IMPLICATIONS OF THE FINDINGS: For those early onset cancer survivors, who received IVF/ICSI treatments, the probability of live birth was not different from siblings who received IVF/ICSI treatments. However, an overall decreased LBR, irrespective of IVF/ICSI treatments, was observed in cancer survivors compared to siblings, indicating that cancer survivors receiving IVF/ICSI treatments in our study consisted of a selected group with at least a moderate ovarian reserve. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a grant from the Cancer Foundation (Finland) (grant number 130079) and by a grant from LähiTapiola. The authors have no potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Prolactin and thyrotropin responses to thyrotropin-releasing hormone in patients with secondary amenorrhea: the effect of bromocriptine.

Prolactin (PRL) and thyrotropin (TSH) responses to a 200 mug intravenous thyrotropin-releasing hormone (TRH) bolus were measured by radioimmunoassay in 11 women with hyperprolactinemic amenorrhea and 9 with normoprolactinemic amenorrhea. In all cases, the tests were carried out under basal conditions and repeated during bromocriptine treatment. In women whose basal PRL level was normal; TRH caused a maximal PRL increment of 85 +/- 25.2 mug/l (mean +/- SE), while those women whose basal PRL level was raised showed a smaller increase (5.2 +/- 11.9 mug/l) (P=0.02). The peak levels were not significantly different in these two groups (95.0 +/- 26.7 and 134.6 +/- 35.9 mug/l) (P is greater than 0.1). During bromocriptine treatment, the raised PRL levels decreased in all cases, but levels over 30 mug/l remained in 3 patients, one of whom turned out to have a pituitary tumor. Prolactin responses to TRH were markedly inhibited in normoprolactinemic patients by the dose of bromocriptine used. The mean maximal net increase of PRL was 2.0 +/- 0.9 mug/l in normoprolactinemic patients and 11.0 +/- 8.1 mug/l in hyperprolactinemic patients taking bromocriptine. After TRH stimulation during bromocriptine, the peak PRL levels in hyperprolactinemic patients were higher (32.7 +/- 10.5 mug/l) than in normoprolactinemic patients (7.2 +/- 1.5 mug/l). Unlike what has been described for hypothyroid patients, the basal TSH level in euthyroid amenorrhea patients was not affected by bromocriptine, and we found that bromocriptine has no effect on the TRH-TSH response.

Prolactin and testosterone: independent circulating levels in hyperprolactinemic and normoprolactinemic amenorrhea. The effect of prolactin suppression by bromocriptine.

In order to elucidate the pituitary regulation of the female testosterone secretion, we studied by radioimmunoassay the circulating prolactin (PRL) and testosterone-dihydrotestosterone (T-dT) levels in 12 hyperprolactinemic and 12 normoprolactinemic patients with secondary amenorrhea. After the basal levels had been recorded, each patient was given bromocriptine for two weeks, 2.5 mg twice daily, and repeat estimations of the PRL and T-dT levels were done. We found no significant difference in the basal T-dT levels between normoprolactinemic and hyperprolactinemic patients, and no significant correlation between the PRL and T-dT levels in either group. Although the PRL levels of the hyperprolactinemic patients were greatly suppressed by bromocriptine, the T-dT levels showed no systematic change. In normoprolactinemic patients, the T-dT concentrations were somewhat lower during bromocriptine treatment, but the difference from basal levels was not statistically significant (0.05 less than P less than 0.1). Our results suggest that in patients with secondary amenorrhea PRL does not interfere directly with T-dT secretion, or vice versa.

Bromocriptine increases plasma estradiol-17 beta concentration in amenorrhea patients with normal serum prolactin.

In a series of 23 patients bromocriptine increased the plasma estradiol-17 beta level from 44.0 +/- 9.5 (mean +/- SE) to 144.1 +/- 31.8 pg/ml after 3 - 5 weeks' treatment (p less than 0.01). In normoprolactinemic patients (N = 12) the level increased from 59.6 +/- 16.3 to 186.5 +/- 50.5 pg/ml (p less than 0.05), and in hyperprolactinemic patients (N = 11) the corresponding values were 27.0 +/- 6.2 and 97.8 +/- 34.6 pg/ml (p less than 0.05). Bromocriptine treatment did not significantly alter the FSH and LH levels. The results suggest that bromocriptine treatment induces endocrine recovery also in patients whose clinical findings give no indication of prolactin suppression.

Sex hormones in amenorrheic women with alcoholic liver disease.

Urinary excretion of estrogens and plasma concentrations of estrone, estradiol, LH, FSH, PRL, progesterone, testosterone, and sex hormone binding globulin were measured in nine chronic alcoholic women with cirrhosis or alcoholic fatty liver. They were aged 24-40 yr and all had secondary amenorrhea which had lasted for at least 3 months. The response of pituitary gonadotropin secretion to administration of LHRH and estradiol benzoate and of PRL secretion to TRH were also investigated. Urinary excretion of estrogens in the alcoholic women with liver disease was similar to that in normal postmenopausal women and less than half that in normal women of the same age in the midfollicular phase of the menstrual cycle. Plasma estradiol levels in the alcoholic women were lower than in the menstruating women but higher than in the postmenopausal women, whereas their plasma estrone levels were higher than in the menstruating women. Plasma concentrations of progesterone and testosterone in the alcoholic women did not differ from those in the postmenopausal women but were lower than in the menstruating women. In spite of the relative estrogen deficiency plasma LH and FSH levels were not elevated in the alcoholic women. The responses of LH and FSH to LHRH were similar in the patients and in the menstruating women. Intramuscular administration of estradiol benzoate did not increase plasma LH and FSH concentrations in the alcoholic women. Hyperprolactinemia was not found and there were no differences in the PRL responses to TRH between the patients and the control groups. In conclusion, disturbed regulation of gonadotropin secretion is an important factor in the genesis of estrogen deficiency and amenorrhea in alcoholic women with liver disease, although ovarian function may also be directly impaired.

Effects of danazol and lynestrenol on serum lipoproteins in endometriosis.

The treatment of endometriosis with danazol or lynestrenol decreased cholesterol content of plasma high-density lipoproteins by 50% and 32%. There were simultaneous increases in low-density lipoprotein cholesterol content of 51% and 19%. We suggest that changes induced by lynestrenol are due to progestational activity, while in the case of danazol both antigonadotropic and androgenic activities are involved.

Metabolic impact of adding medroxyprogesterone acetate to conjugated estrogen therapy in postmenopausal women. The Menopause Study Group.

OBJECTIVE: To evaluate the impact of different dosages of medroxyprogesterone acetate (MPA) on metabolism and hemostasis in postmenopausal women treated with conjugated estrogens. METHODS: In this prospective, double-blind study, 525 women were randomized to five treatment groups at 26 sites in the United States and Europe. All participants received 0.625 mg conjugated estrogens daily for up to 13 cycles; four groups also received MPA, either 2.5 or 5.0 mg/day continuously or 5.0 or 10.0 mg/day for the last 14 days of each cycle. Effects on lipid and carbohydrate metabolism and coagulation were evaluated. RESULTS: Beneficial changes in plasma lipid levels occurred in all groups, but were greatest with conjugated estrogens alone (P < or = .05). Fasting glucose and insulin levels were significantly lower and the insulin response to glucose challenge was significantly blunted in all groups (P < or = .05). No major changes of clinical significance occurred in hemostatic levels. CONCLUSIONS: Metabolic levels were not affected adversely by the addition of MPA to conjugated estrogens, but some beneficial changes were greater with conjugated estrogens alone. Hemostatic levels were not affected.

Progestins.

The history of progesterone and hormone replacement therapy goes back to 1934 when Butenandt obtained crystalline progesterone and Kaufmann started to treat ovariectomized women with both estrogens and progesterone (Table 1). Today synthetic perorally active 19-nortestosterone and 17-alpha-hydroxyprogesterone derivatives are used in addition to contraception and hormone replacement therapy in a variety of gynecological disorders. In hormone replacement therapy progestin is added only to prevent development of hyperplasia of the endometrium and its consequences. However, because progestins may cause both subjective and metabolic adverse effects minimum effective antiproliferative doses are recommended. The duration of the progestin phase cannot be shortened to less than 10 days whereas the frequency of administration apparently can be reduced without increased risk of hyperplasia. Development of new modes of administration may further help in reduction of the doses.

Comparison of two hormone replacement regimens--influence on lipoproteins and bone mineral content.

Two hormone replacement therapy regimens were tested in a double-blind clinical trial involving 49 patients. In both cases the oestrogen component was 2 mg oestradiol valerate. This was administered for 21 days and sequentially combined for 10 days with either 0.5 mg norgestrel + (Cyclo-Progynova) or 1 mg cyproterone acetate (SH D 461 A). Each treatment cycle was followed by a 7-day tablet-free period. Both regimens proved to be equally effective in alleviating climacteric complaints. However, the low-density-lipoprotein cholesterol lowering effect of SH D 461 A was found to be superior to that of Cyclo-Progynova. There were no changes in bone mineral content during the one-year treatment period with either combination.

A randomized, double-blind, multicentre study comparing the clinical effects of two sequential estradiol-progestin combinations containing either desogestrel or norethisterone acetate in climacteric women with estrogen deficiency symptoms.

OBJECTIVES: The aim of this study was to compare a new estradiol-desogestrel (E2-DG) regimen with an E2-norethisterone acetate (NETA) combination (Trisekvens) regarding the treatment of menopausal complaints, bleeding pattern, histology of the endometrium and the occurrence of adverse experiences. METHODS: A total of 310 peri-/postmenopausal women with climacteric symptoms were randomly allocated to oral sequential treatment with either the E2-DG combination (1.5 mg E2 for 24 days with 0.15 mg DG for the last 12 days followed by 1 placebo tablet for 4 days) or with the E2-NETA combination (Trisekvens, 2 mg E2 for 22 days with 1 mg NETA for the last 10 days followed by 1 mg E2 for 6 days). Treatments were administered double-blind for 12 cycles of 28 days. RESULTS: One hundred and four women, 48 in the E2-DG group and 56 in the E2-NETA group, discontinued the study due to bleeding irregularities and various adverse effects. Both treatments reduced menopausal symptoms and complaints effectively and almost equally. The alleviation of perspirations and the improvement of general fitness were more apparent (P = 0.009) during cycle 1 with the E2-NETA treatment but were greater (P < 0.02) during the last 9/10-12 cycles of E2-DG treatment compared to E2-NETA. Regular withdrawal bleeding appeared in 93% and 90% of the women during treatment with E2-DG and E2-NETA, respectively. Intermenstrual bleeding occurred in 8% of women receiving E2-DG and in 13% of women treated with E2-NETA. The corresponding figures for intermenstrual bleeding-spotting were 21% and 22%. Secretory endometrium was detected in 65% and 54% of the samples taken at the end of treatment with E2-DG and E2-NETA, respectively. No hyperplasia or atypia was found. No serious adverse events related to treatment occurred. CONCLUSIONS: Both regimens alleviated effectively menopausal complaints and did not induce hyperplasia of endometrium. The minor differences recorded between the two regimens were probably due to the differences in their composition concerning the amount of estradiol and its distribution along the cycle, the amount and type of progestin and the length of estradiol/progestin combination phase.

A novel oestradiol--desogestrel preparation for hormone replacement therapy: effects on hormones, lipids, bone, climacteric symptoms and endometrium.

Desogestrel is a strong progestogen with low androgenicity which has so far been used only in oral contraceptives. We studied the feasibility of administering desogestrel in combination with oestradiol as hormone replacement therapy (HRT). Thirty women received a sequential combination containing 1.5 mg micronised oestradiol (24 days) and 0.15 mg desogestrel (last 12 days of cycle) for 6 months. At that stage 6 of the women dropped out; the remaining 24 were studied for a total of 12 months. The treatment alleviated vasomotor symptoms effectively in all the women and induced regular withdrawal bleeding in 86% of them. Secretory changes were observed in the endometria of 16 of the 20 women with adequate endometrial samples assessed after 12 months of treatment. No signs of hyperplasia or atypia were found. Six months of treatment resulted in a decrease in the mean serum follicle-stimulating-hormone concentration from 66.2 (+/- 4.3, S.E.M.) to 23.3 (+/- 3.1) IU/l and a rise in the oestradiol and sex-hormone-binding globulin concentrations from 87.9 (+/- 13.7) to 233.1 (+/- 20.4) pmol/l and from 52.1 (+/- 4.6) to 70.2 (+/- 5.6) nmol/l, respectively. Testosterone levels decreased. There were significant reductions in serum total and low density lipoprotein (LDL) cholesterol and triglycerides. After 12 months of treatment high-density lipoprotein (HDL) cholesterol values did not differ significantly from the pretreatment levels. The HDL/LDL and HDL/total cholesterol ratios increased. The treatment reduced bone turnover as indicated by decreases in bone alkaline phosphatase and osteocalcin serum levels and by lowered urinary calcium/creatinine and hydroxyproline/creatinine ratios. An increase of about 2% in forearm bone mineral density was also observed. This new oestradiol-desogestrel preparation therefore appears to be a promising alternative form of HRT. It alleviates climacteric symptoms effectively, exhibits favourable effects on serum lipids and lipoproteins and prevents bone loss.

New natural oestradiol/cyproterone acetate oral contraceptive for pre-menopausal women.

Fifty (50) healthy ovulating women aged between 35 and 47 yr (mean age 39) were randomly allocated to one of two groups treated with biphasic formulations of either oestradiol valerate/cyproterone acetate (Group A) or oestradiol valerate/norethisterone (Group B). A double-blind design was used during the first 6 mth of treatment. In Group A, 21 out of 26 women (81%), and in Group B, 16 out of 24 (67%) completed the first year of treatment. No pregnancies occurred. The mid-cycle serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) peaks were suppressed, but there were no differences between the pretreatment serum oestradiol values and those observed during the treatment cycles. The serum progesterone values indicated that only one ovulatory cycle occurred during the first year in Group A, while there were 11 in Group B. Ultrasonic studies revealed follicular growth during treatment in both groups, most follicles becoming atretic or persistent without ovulation. No significant changes were observed in 11 coagulation factors studied in 16 women in Group A. Serum total cholesterol decreased by about 10% in both groups. In Group A bleeding became scantier and dysmenorrhoea disappeared. The incidence of spotting varied between 30% and 40%, but it is important to note that the total number of bleeding days per cycle fell. The oestradiol valerate/cyproterone acetate combination was thus found to inhibit ovulation, provide tolerable cycle control and to be free from adverse metabolic side effects.

Oral contraceptive containing natural estradiol for premenopausal women.

An open multicenter trial was performed in six centers in Finland to study the efficacy, safety and acceptability of a new biphasic oral contraceptive pill containing natural estradiol and cyproterone acetate. The participants were 288 women with a mean age of 39.3 +/- 3.4 years (range 30-49) who were willing to use the new pill as their only contraceptive method. In total, 23% of the women were smokers. The cumulative experience was 2800 treatment cycles during the first year. The net 12-month continuation rate was 63%. One pregnancy occurred in a woman who lost 5 tablets in the second treatment cycle, which gives a 12-month cumulative pregnancy rate of 0.4%. Serum progesterone values, determined twice during the third treatment cycle, showed ovulation inhibition in 95% of women. There were no serious side effects. Intermenstrual bleeding was recorded by 35.5% and 24.5% of women at 3 and 12 months, respectively. The bleedings became scantier in most women and dysmenorrhoea disappeared. No changes were observed in total and high density lipoprotein cholesterol concentrations after 1 year. With the exception of intermenstrual spotting, the efficacy, safety and acceptability of the new pill was almost as good as that of the modern low dose oral contraceptives. This is the first pill containing natural estradiol that has gained clinical acceptance and which can also be prescribed for smokers over 35 years old until the climacteric.

PIP: Gynecologists accepted 288 women aged 30-49 from six different clinics in Finland into a clinical trial of a new biphasic oral contraceptive (OC) containing natural estradiol and cyproterone acetate (manufactured by Leiras Oy, Turku, Finland). They aimed to determine the contraceptive efficacy, safety, cycle control, and acceptability of this OC. 24% of the women smoked cigarettes. Gastrointestinal upset in one woman led to failure to take the fourth and fifth tablets at the beginning of the second treatment cycle. She became pregnant (pregnancy rate = 0.35%). 9.3% and 13.3% of women missed pills at the 3-month and 12-month follow-up visits, respectively. 95% of the women had serum progesterone values lower than 9 nmol/l, indicating ovulation suppression. OC use reduced excessive menstrual bleeding (30% before study vs. 3% after 13 cycles; p 0.0005). It also reduced dysmenorrhea (14% vs. 2%; p 0.0005). No one had any serious side effects. The minor side effects (breast tension, edema, headache, and depression) subsided with time. The 12-month continuation rate was 63%. The main reason for discontinuation was side effects (25.9%). Total serum cholesterol and HDL-cholesterol levels did not change significantly, while serum triglyceride levels increased from 0.92 to 1.14 mmol/l (p = 0.02). Even though serum potassium and creatinine levels changed significantly, the 13-month levels fell within the normal range. These findings show that this new OC is an effective contraceptive for premenopausal women. The absence of adverse effects on the blood coagulation system and lipoprotein metabolism make this new OC safe for smokers.

Clinical and lipid metabolic effects of unopposed oestrogen and two oestrogen-progestogen regimens in post-menopausal women.

No differences in the clinical effects on climacteric complaints of an unopposed oestrogen and two oestrogen-progestogen regimens were observed in a double-blind cross-over study. Only 4 out of 18 women with an intact uterus had withdrawal bleeding during oestradiol valerate (2 mg/day) treatment alone, but 14 out of 18 had regular bleeding during the two oestrogen-progestogen regimens (oestradiol/medroxyprogesterone acetate and oestradiol/levonorgestrel (LNG], each of which prevented the development of endometrial hyperplasia. High-density-lipoprotein cholesterol (HDL-CH) concentration remained 6% above the initial level and the atherogenic index (low-density-lipoprotein (LDL) cholesterol to HDL-CH ratio) improved significantly during the oestradiol/medroxyprogesterone acetate regimen, while the HDL-CH concentration fell by 20% in relation to the initial level and there was a deterioration in the atherogenic index during the oestradiol/LNG regimen. The data suggest that both of these oestradiol/progestogen combinations are clinically as effective and well-tolerated as oestradiol alone, but that combined oestradiol/medroxyprogesterone acetate causes fewer adverse lipid metabolic effects than the oestradiol/LNG combination.

Can progestin be limited to every third month only in postmenopausal women taking estrogen?

We evaluated whether a progestin, added for 14 days every 3 months to estrogen replacement therapy, is capable of preventing the development of endometrial hyperplasia in postmenopausal women during a treatment period of 2 years. Postmenopausal women (263) in 10 hospitals and medical centers in Finland participated in this non-randomized prospective multicenter trial. The women received estradiol valerate 2 mg daily for 84 days and 20 mg of medroxyprogesterone acetate daily for days 71-84 followed by seven drug-free tablets. This regimen was repeated four times per year. The first year of treatment was completed by 227 (86%) women and the second year by 143 out of 146 women. The incidence of unscheduled and heavy bleedings was higher in women who were postmenopausal for less than 3 years. Endometrial biopsies demonstrated progestational response in 64% at 12 and 24 months, respectively. The 3 month regimen prevented development of endometrial hyperplasia but was not able to restore a hyperplastic endometrium to normal.

Ovulation inhibition by a new low-dose progestagen.

PIP: A new synthetic progestagen, Org 2969 (13-ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-17-ol) was administered to 9 healthy normally menstruating women. 3 subjects (Group 1) ingested .030 mg, while 6 (Group 2) ingested .015 mg of the compound daily on Days 1-20 of 1 menstrual cycle. The previous menstrual cycle served as control. Serum follicle stimulating hormone, luteinizing hormone, progesterone, and estradiol analyzed on the Days 8-23 showed that all the treatment cycles of Group 1 were anovulatory and 2 subjects from Group 2 had ovulatory cycles. Serum activities of aspartase amino transferase, alanine amino transferase, alkaline phosphatase, gamma glutamyl transpeptidase, and bilirubin concentration determined on Days 8, 15, and 23 did not reveal any change in liver function. Serum cortisol measured on Days 8 and 23 remain unchanged. 1 subject from Group 1 and 3 from Group 2 experienced bleeding irregularities.^ieng

Effects on the hemostatic system and liver function in relation to Implanon and Norplant. A prospective randomized clinical trial.

In this prospective randomized clinical trial, two long-term contraceptive implants were studied with respect to hemostasis and liver function in 86 healthy young women. The two implants used were Implanon, containing the progestagen etonogestrel (the biologically active metabolite of desogestrel) and Norplant, the implant containing the progestagen levonorgestrel. The results of the trial showed that both implants had similar small effects on the hemostatic system that are not suggestive of a tendency towards thrombosis. The effect on liver function was characterized by increases in total bilirubin and gamma-glutamyl transferase and decreases in alanine aminotransferase and aspartate aminotransferase.

The adverse hemodynamic effects of anesthesia, head-up tilt, and carbon dioxide pneumoperitoneum during laparoscopic cholecystectomy.

BACKGROUND: The increased intra-abdominal pressure during pneumoperitoneum, together with the head-up tilt used in upper abdominal laparoscopies, would be expected to decrease venous return to the heart. The goal of our study was to determine whether laparoscopy impairs cardiac performance when preventive measures to improve venous return are taken, and to analyze the effects of positioning, anesthesia, and increased intra-abdominal pressure. METHODS: Using invasive monitoring, hemodynamic changes were investigated in 15 ASA class I or II patients under isoflurane-fentanyl anesthesia during laparoscopic cholecystectomy. Before laparoscopy, the patients received an intravenous (IV) infusion of colloid solution if cardiac filling pressures were low, and their legs were wrapped from toes to groin with elastic bandages. Measurements were taken while the patients were awake in the supine (baseline) and head-up tilt (15-20 degrees) positions, and after the induction of anesthesia in the same positions. Measurements were repeated at regular intervals during laparoscopy (intra-abdominal pressure at 13-16 mm Hg), after deflation of the gas, and in the recovery room. RESULTS: With the passive head-up tilt in awake and anesthetized patients, the cardiac index (CI), stroke index (SI), central venous pressure (CVP), and pulmonary capillary wedge pressure (PCWP) decreased, and systemic vascular resistance increased. With the patient under anesthesia, SI decreased, but CI did not change significantly as a result of the compensatory increase in heart rate. Carbon dioxide (CO2) insufflation at the start of laparoscopy produced increases in CVP and PCWP as well as mean systemic and mean pulmonary arterial pressures without changes in CI or SI. Toward the end of the laparoscopy, CI decreased by 15%. The hemodynamic values returned to nearly prelaparoscopic levels after deflation of the gas, and CI was elevated during the recovery period, whereas systemic vascular resistance was decreased in comparison with the baseline. CONCLUSIONS: By correcting relative dehydration and preventing the pooling of blood, CI decreased less than 20% during pneumoperitoneum as compared with the baseline awake level. The head-up positioning accounts for many of the adverse effects in hemodynamics during laparoscopic cholecystectomy.