Reproductive Urinary Metabolites during the Perimenopause

Table 1: Comparison of patients <38 by FSH level ⬍38 and FSH ⱖ10 ⬍38 and FSH ⬍10 n⫽34 n⫽173 P value Mean Age (yrs) Age Range (yrs) Mean FSH (mIU/mL) AFC Oocytes (number) Gonadotropins (IU) Peak E2 (pg/mL) Average # tx IR PR

33.8 ⫾ 1.7 23–37 11.5 ⫾ 0.25 9.18 ⫾ 0.31 8.8 ⫾ 0.54 4556 ⫾ 268 1572 ⫾ 125 2.06 ⫾ 0.09 46.6% 57.6%

33.1 ⫾ 1.2 24–37 6.2 ⫾ 0.10 15.2 ⫾ 0.76 14.4 ⫾ 0.73 2775 ⫾ 75 2316 ⫾ 68 2.05 ⫾ 0.03 48.4% 62.4%

NS NA ⬍.001 ⬍.005 ⬍.001 ⬍.001 ⬍.005 NS NS NS

67 million/ml; Sperm motility (%) were 48 vs. 53%, and Sperm morphologies were 6% normal vs. 7%. Results: Pregnancy rates for the Ac group were statistically similar to the C (Ac 49.5% vs. 46.3%). Summary statistics are in the table below. There were no statistically significant differences between the Controls and Acupuncture treated groups: Control Acupuncture Not Not Control Acupuncture Pregnant Pregnant Pregnant Pregnant Number Eggs retrieved Number Fertilized Normally Number Embryo Transferred Number Frozen Day of Transfer

12.8 7.1 3.1 1.4 3.0

12.5 7.2 3.3 1.2 3.1

15.4 7.9 3.4 2.3 3.1

15.0 8.5 3.7 1.7 3.1

Table 2: Comparison of patients by age and FSH level ⬍38 and FSH ⱖ10 ⬎38 and FSH⬍10 n⫽34 n⫽62 P value Mean Age (yrs) Age Range (yrs) Mean FSH (mIU/mL) AFC Oocytes (number) Gonadotropoins (IU) Peak E2 (pg/mL) Average # tx IR PR

33.8 ⫾ 1.7 23–37 11.5 ⫾ 0.25 9.18 ⫾ 0.31 8.8 ⫾ 0.54 4556 ⫾ 268 1572 ⫾ 125 2.06 ⫾ 0.09 46.6% 57.6%

39.7 ⫾ 1.4 38–43 6.4 ⫾ 0.17 11.26 ⫾ 0.61 12.02 ⫾ 0.58 3928 ⫾ 112 2177 ⫾ 106 2.85 ⫾ 0.07 22.7% 48.6%

⬍.05 NA ⬍.001 ⬍.05 ⬍.05 ⬍.05 ⬍.05 ⬍.001 ⬍.001 NS

O-7 Acupuncture: Impact on Eggs & Embryos of IVF Patients. Paul C. Magarelli, M.D., Ph.D.a, Diane Cridennda, L.Ac.b, Mel Cohen, MBAa. aReproductive Medicine & Fertility Center, Colorado Springs, CO. bEast Winds Acupuncture, Colorado Springs, CO. Background: Each IVF program strives to improve reproductive outcomes (low ectopic rates, low miscarriage rates and improved take home baby rates – live births). Usually the approach to these improvements are changes in IVF protocols, media adjustments in the IVF lab, patient selection, and subtle nudges towards egg donors for poor responders. Another approach has been the inclusion of alternative medical modalities: acupuncture, massage therapy, stress reduction techniques, herbal medicine. We, and others, have chosen to incorporate Acupuncture into our IVF treatment protocols. Recently we presented three studies that demonstrated improvements in pregnancy rates and birth outcomes in Good and Poor IVF Responders with the inclusion of two specific Acupuncture Protocols (Steiner-Victorin and Paulus et. Al). In the Poor Responders study we demonstrated a positive adjustment to pregnancy rates with improvements in Poor Responders group pregnancy rates (PR) equivalent to Good Responders. In the Good Responders study we demonstrated a trend towards improved PR (5% above controls, not significant at p ⬍ 0.05). In both groups, significantly more live births per cycle start and per pregnancy were found (p ⬍ 0.05). Understanding the root cause of these improvement remains our research focus. Objective: In this research, we examine the impact of Acupuncture on the embryology characteristics of our IVF patients, i.e., are there changes in the numbers of eggs generated, embryos fertilized, embryos transferred or remaining embryos for freezing. Materials and Methods: In this study 178 IVF cycles were reviewed in a retrospective fashion. Patients demographics, years infertile, age of male partners, sperm parameters, Day 3 FSH, Pulsatility Indices, Weight, BMI, infertility diagnoses, IVF treatment protocols were statistically similar for both the Controls (C) and Acupuncture (Ac) treatment groups. All patients that completed an IVF cycle (retrieval, transfer) were included. There were 97 in the C group (no acupuncture) and 81 in the Ac group. For the C vs. Ac groups a summary of their statistics are as follows: Mean Age was 32.6 vs. 32.7, Day 3 FSH was 5.5 vs. 6.4, Pulsatility Indices for right and left uterine arteries were 1.5 and 1.2 vs. 1.4 and 1.0; Sperm counts were 69 vs.

FERTILITY & STERILITY威

Conclusions: There were no discernable statistical differences between embryology characteristics in patients treated with or without Acupuncture. Further studies of Traditional Chinese Medicine modalities of treatment are underway. We are organizing a multicenter prospective study to confirm our observations.

O-8 Reproductive Urinary Metabolites during the Perimenopause. J.E. Jackson, M.L. Evans, D. Moore, M.I. Cedars Department of Obstetrics and Gynecology, University of California, San Francisco, USA. Background: The exact nature of hormonal changes in the perimenopausal period is not fully understood. The evaluation of urinary metabolites of reproductive hormones allows a longitudinal non-invasive measure of hormone secretion. Prior studies have shown that evaluation of urinary metabolites is a viable method of assessing menstrual function, but only a minority of studies evaluated these metabolites in perimenopausal women. Objective: This study aims to compare reproductive urinary metabolite secretion in regularly cycling perimenopausal women versus younger women. Materials and Methods: Daily morning urine samples were obtained from normally cycling women ages 25-50 years old for an entire menstrual cycle, and were analyzed by ELISA for estrone-3-gluduronide (E1G) and pregnanediol-3-glucuronide (PdG). Day of ovulation was assessed with ultrasound monitoring. Results: Urine samples were obtained from a total of 109 women, 28 were between 25 and 35 years old (mean age 27.9 ⫾ 3.8), and 81 were between 35 and 50 years old (mean age 40.7 ⫾ 3.9). There were significantly lower progesterone levels in the older versus the younger group throughout the entire cycle as well as during the follicular and the luteal phases. In addition, there was significantly lower estrogen in the older versus the younger group during the luteal phase (82.4 nmol/L vs 106.5 nmol/L, p⫽0.015). The mean length of the follicular phase was significantly shorter in the older group (13.9 days versus 15.5 days, p⫽0.006) but there was no significant difference in the average length of the luteal phase between groups. AUC of Urinary Metabolites

E1G total* E1G Follicular* E2 Luteal* PdG total* PdG Follicular* PdG Luteal*

Younger (n⫽28)

Older (n⫽81)

P value**

94.0 ⫾ 38.5 80.5 ⫾ 34.5 106.5 ⫾ 52.1 10.9 ⫾ 4.4 5.6 ⫾ 2.3 17.2 ⫾ 8.7

86.2 ⫾ 32.1 87.5 ⫾ 38.3 82.4 ⫾ 30.7 6.2 ⫾ 3.0 2.6 ⫾ 1.3 10.5 ⫾ 5.0

0.326 0.361 0.015 ⬍0.001 ⬍0.001 ⬍0.001

* Mean value of AUC, ⫾ SD. Values are standardized by cycle length. ** P value calculated by log transformation

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Follicular and Luteal Phase Lengths

Length of Follicular Phase* (days) Length of Luteal Phase* (days)

Younger (n⫽28)

Older (n⫽81)

P value**

15.5 ⫾ 2.8 13.0 ⫾ 2.1

13.9 ⫾ 2.9 12.4 ⫾ 2.1

0.006 0.2376

* Mean value, ⫾ SD ** P value calculated by log transformation Conclusions: This study confirms that regularly cycling perimenopausal women have a lower level of progesterone throughout the entire cycle, as compared to younger controls. A new finding in this study is that perimenopausal women are in a relatively hypoestrogenic state during the luteal phase, as compared with their younger controls. Potentially, this hypestrogenic state could lead to menopausal symptoms (hot flashes, moodiness) that have been previously mistaken for worsening “premenstrual syndrome”. In addition, this relatively hypoestrogenic state and other hormonal differences may explain the subfertility seen in the perimenopause, via decreased implantation rates.

O-9 Fertility and Malpractice: A Review of Case Law in State Courts. R.D. Dickersona, A.B. Pintoa, J.A. Curryb. aBaylor University Medical Center, Department of Obstetrics and Gynecology, Dallas, TX. bBaylor University, Department of Political Science, Waco, TX. Background: Fertility issues have received relatively little attention within the broader subject of medical malpractice, but current trends suggest the need for better understanding of the subject. Objective: We review state appellate court rulings concerning fertility (including in-vitro fertilization) and state medical malpractice laws to identify and explain common patterns and emerging trends. Methods: A Lexis-Nexis key word search of appellate and supreme court decisions in all fifty states over the past ten years identified cases containing “fertility,” “in vitro,” “fertilization,” “insemination,” and “malpractice.” All cases were analyzed and classified into categories by subject matter. Results: The search produced 259 cases on the key words fertility, in vitro, fertilization, and insemination. Eighty-four (84) of these cases also involved medical malpractice. These 84 cases were grouped into distinct categories by subject and outcome. Conclusions: State laws vary in their treatment of medical malpractice and fertility cases. A significant cluster of cases involve claims for diagnostic failures and delay, while an emerging body of case law focuses on claims resulting from in vitro fertilization and other artificial insemination practices. Controversies stemming from laws protecting the fetus are also evident. Supported By: None. O-10 Degree of Re-Expansion is a Good Predictor of Outcome with FrozenThawed Blastocysts. A.R. Criniti, J.D. Lamb, A. Khabani. University of Washington Medical Center, Seattle, WA. Background/Significance: Multiple gestation is the most serious adverse outcome of ART. Reducing the number of embryos transferred is essential. Confidence in cumulative pregnancy rates, including both fresh and frozen transfer, is paramount. Integral to the success of cumulative pregnancy rates is the ability to select the best embryo for transfer. Objective: The objective of this study was to review our clinic’s experience with frozen-thawed blastocyst transfers. Materials and Methods: Cryopreserved blastocyst cycles (n⫽52) were reviewed from 1/2004 to 8/2004. Our clinic uses a Menezo 2 step freezing protocol and a slow 7 step re-hydration protocol. Blastocysts are frozen on either day 5 or 6 of development. Only blastocysts of BB or better quality by Gardner’s criteria are frozen. We compared frozen-thawed blastocysts that 1) demonstrated no evidence of re-expansion, 2) demonstrated partial re-expansion, and 3) demonstrated complete re-expansion. Main outcome measures included post-thaw survival rate, implantation rate, and pregnancy rate. Implantation rate (IR) was defined as the number of gestational sacs

S10

PCRS Abstracts

with a fetal heartbeat divided bythe number of embryos transferred. Clinical pregnancy rate (PR) was definedby the presence of a fetal heartbeat on ultrasound. Chi-Square testing was used for statistical analysis. Results: Overall survival rate for all frozen-thawed blastocysts was 89% (94/105). Of blastocysts that survived, 86 were considered suitable for transfer. Overall IR and PR were 20.1% and 34.6% respectively. Among blastocysts that were transferred, 38 were unexpanded, 31 were partially re-expanded, and 17 were completely re-expanded. Blastocysts that were completely re-expanded had significantly higher implantation rates than blastocysts that were partially re-expanded (58.6% vs 23.4%, p⬍.05) or that were unexpanded (58.6% vs 7.9%, p⬍.001). Of pregnancies that occurred, 42%,were twins. All twin pregnancies resulted from the transfer of two completely expanded blastocysts. Conclusions: Blastocysts can be frozen and thawed with good survival rates. Degree of re-expansion is an excellent predictor of outcome in frozen blastocyst cycles. In fact, the twin rate is relatively high when two completely expanded blastocysts are transferred. Consideration may be given to transferring only one thawed blastocyst when there is evidence of complete re-expansion. O-11 Metformin Therapy Improves Ovarian Morphology in Polycystic Ovary Syndrome Patients (PCOS). A. Bayrak, H. Terbell, R. UrwitzLane, F.Z. Stanczyk, R.J. Paulson. Background: We have previously shown a significant improvement in biochemical markers of PCOS with low dose and short course metformin therapy. Anti-Mullerian Hormone is a marker of ovarian reserve and may be involved in the pathophysiology of PCOS. Whether there is an association between AMH and insulin resistance is unknown. In addition, acute effects of metformin on AMH and ovarian morphology are not documented. Objective: To prospectively compare AMH levels in insulin resistant (IR), non-insulin resistant (NIR) PCOS patients, and controls; to evaluate the acute effects of metformin therapy on AMH levels and ovarian morphology. Materials and Methods: We prospectively included five non-insulin resistant and five insulin resistant PCOS patients evaluated in our Reproductive Endocrinology Clinic. Mean age and body mass index (BMI) in PCOS patients were 29.5⫾4.8 and 30.2⫾4.5, respectively. Patients underwent blood sampling for AMH at baseline and following metformin therapy at 850mg for one week. Baseline AMH levels were also compared to age matched non-PCOS controls (n⫽ 4). Ovarian morphology as assessed by antral follicle count was recorded prior to and after metformin therapy. For statistical analysis t-test was used; p⬍0.05 was considered statistically significant. Study was approved by the IRB. Results: AMH levels were statistically significantly higher in PCOS patients compared to controls (2.81⫾1.79 ng/ml vs. 0.95⫾1.17 ng/ml, p⬍ 0.05). AMH levels were similar between insulin resistant PCOS patients, compared to non insulin resistant PCOS patients (2.77⫾1.91ng/ml vs. 2.85⫾1.89 ng/ml, p⬎0.05). One week of metformin therapy did not alter AMH levels (p⬎0.05). However, there was a statistically significantly decrease in the number of antral follicles following one week of metformin therapy (38.8⫾19.3 vs. 23.1⫾7.4, p⬍0.005). Conclusions: AMH levels are increased in PCOS patients compared to non-PCOS controls, but are not associated with insulin resistance. Metformin exerts an acute effect on ovarian morphology, which might explain the observed improvement in response to ovulation induction agents. O-12 IVF Predictor Variables Differ by Ethnicity. K.J. Purcell, M. Schembri, S. Shen, M. Croughan, V.Y. Fujimoto. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, CA 94115. Background: Success of patients undergoing in vitro fertilization (IVF) is negatively impacted by variables including age, day 3 FSH, and specific infertility diagnosis. The effect of these variables has been established largely from studies of Caucasian patients. As Asian patients have altered IVF outcomes compared to Caucasians, we sought to define the influence of these prognostic indicators for the two ethnicities. Objective: To determine if the variables predicting poor IVF outcome differed between Asian and Caucasian patients.

Vol. 83, Suppl 2, May 2005