12th World Congress on Human Reproduction, Venice Italy March 2005

Paul C. Magarelli, M.D., Ph.D. Reproductive Medicine & Fertility Center, Colorado Springs, Diane Cridennda, L.Ac. East Winds Acupuncture,

Mel Cohen, MBA Reproductive Medicine & Fertility Center, Colorado Springs

Abstract

Take Home babies’ rates (THB) have been the sine quo non of IVF outcomes. Pregnancy rates (PR) can overestimate the expected success of a high-technology treatment for patients and many clinics use PR as means of marketing their practices. This has caused disillusionment in patients and government regulation (especially in the U.S.). 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 two studies that demonstrated improvements in pregnancy rates in Good and Poor IVF Responders with the inclusion of two specific Acupuncture Protocols (Steiner-Victorin and Paulus et. Al). In the poor responders group we demonstrated a positive adjustment to Poor Responders pregnancy rates (PR) with improvements in PR in the Poor Responders group 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). With these observations noted we have continued our investigation and are reporting on reproductive outcomes in all IVF patients treated with Acupuncture compared to those untreated.

Materials and Methods: In this study 130 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 82 in the C group (non acupuncture) and 48 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. 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, although numerically higher, versus C (50% v 45% at P < 0.05). Ac miscarriage rates (SAB) were statistically lower than the C (8 % vs. 11% at p <0.01). There were no ectopic pregnancies in the Ac group ( P < 0.01). Live Births were significantly better in the Ac v C groups (42% v 38%). A surprising observation was that multiples pregnancies were significantly lower in the Ac vs. C groups (17 % vs. 22%). Average eggs retrieved were statistically similar 15 vs. 15 for Ac and C respectively.

Conclusions: IVF programs can significantly improve their IVF outcomes ( PR, THB, SAB and Ectopic) by adding acupuncture protocols, specifically Steiner Victorin and Paulus. Further studies of Traditional Chine Medicine modalities of treatment are underway. We are organizing a multicenter prospective study to confirm our observations.

Improvement of IVF Outcomes by Acupuncture: Are egg and embryo qualities involved?

Paul C. Magarelli, M.D., Ph.D., ^a Diane Cridennda, L.Ac. ^b, Mel Cohen, MBA ^a

^a Reproductive Medicine & Fertility Center, Colorado Springs, CO ^b East Winds Acupuncture, Colorado Springs, CO

FERTILITY AND STERILITY®, May 2005, VOL 83, SUP 2, Proceeding from the 2005 Pacific Coast Reproductive Society annual meeting in Palm Springs

Objective: In this study, we examine the impact of Acupuncture on the embryology characteristics of IVF patients, i.e., are there changes in the numbers of eggs generated, embryos fertilized, embryos transferred or remaining embryos for freezing in those patients receiving acupuncture therapy.

Design: Retrospective clinical study

Setting: Private infertility practice and Traditional Chinese Medicine practice

Patients: Two hundred eight IVF cycles were reviewed, 95 received acupuncture (Ac) and 113 were controls (C).

Interventions: Patients randomly chose Ac to complement their IVF treatments. Two published Ac protocols were used. Standard IVF protocols were used and done in one clinic by one physician. The MD was not aware of who received Ac in addition to their IVF. After three years the data were collected and analyzed.

Main Outcome Measures: Number of eggs retrieved, number of eggs fertilized normally, number of embryos implanted, number of embryos frozen, number of embryos transferred, day of transfer, number of prior IVF cycles, Day 3 FSH, Pulsatility Indices, weight, infertility diagnoses, IVF treatment protocols, pregnancy rates, SAB rates, ectopic rates, and multiple pregnancy rates.

Results: Number of prior IVF cycles, Day 3 FSH, Pulsatility Indices, Weight, Infertility diagnoses, IVF treatment protocols were statistically similar. Pregnancy rates for the Ac group were statistically significantly higher than the C group (P ≤ 0.05), SAB rates were lower and multiple pregnancy rates were lower (P < 0.06, not statistically significant). Ectopic pregnancy rates were statistically lower in the Ac group (P ≤ 0.05). There were no statistically significant differences between the C and Ac treated groups for the following embryology parameters: number of eggs retrieved, number of eggs fertilized normally, number of embryos implanted, number of embryos frozen, number of embryos transferred, and day of transfer.

Conclusions: There were no discernable statistical differences between embryology characteristics in patients treated with or without Acupuncture. These data suggests that the mechanism of action of Acupuncture on IVF outcomes may be related to affects in the host (the egg provider and the embryo recipient) rather than in direct changes to the eggs retrieved and the embryos created.

Key Words: IVF, acupuncture, adjuvant therapies, electro stimulation acupuncture, embryology, eggs

Acupuncture & IVF Poor Responders: A Cure?

P.C. Magarelli, D.K. Cridennda. Reproductive Medicine & Fertility Center, Colorado Springs, CO.

FERTILITY AND STERILITY®, Proceeding from the 2004 Pacific Coast Reproductive Society annual meeting in Palm Springs

Background and Significance: The utility of acupuncture in the treatment of infertility has been demonstrated in two controlled studies. The first study determined the effect of reducing the Pulsatility Index (PI) of the uterine artery on reproductive outcomes; the second study described a Pre/Post embryo transfer protocol that enhanced overall pregnancy rates (PR). There are no studies that have utilized both techniques.

Objective: The purpose of the study was to determine the influence of these two acupuncture protocols on IVF outcomes and secondly to identify the appropriate patient groups that would most benefit from this adjunctive therapy.

Materials and Methods: In this retrospective study, data was extracted from medical records of patients RE&I clinic & acupuncture clinics between January 2001 and November 2003. All patients completing an IVF cycle with transfer were included. One RE&I provided the IVF care and a consortium of acupuncturists overseen by the author provided the strict acupuncture protocols. PR per transfer were the endpoints measured. Data was analyzed by student’s t test and Multiregression with Wilcox ranking (MRW).

Results: 147 patients were included in the study and of those 53 had Acupuncture (Ac) and 94 did not (Non-Ac group). Demographic data between these Ac and Non-Ac groups respectively indicated remarkable equity (Table 1). Fertility Factors also demonstrated equity and there were no differences in Diagnoses, IVF Protocols and type of Gonadatrophin protocols used.

Factors that demonstrated significance were: Length of time infertile, Peak FSH, PI for total group without MRW; PI for MRW groups reversed this (Table 2) and finally average: Sperm Morphology, Peak E2, Peak P4 prior to HcG: and endometrial thickness. PR before Wilcox ranking were the same: 40% v 38%. MRW analysis revealed FSH, Length of time trying to get pregnant, Sperm Morphology and E2 levels as significant: 6.5, 4.1, 4.0 and 1.6 respectively. When the Ac group was modified (15 Ac patient dropped), PI was elevated from 1.76 to 1.94 resulting in a significant elevation compared to the Non-Ac group, p < 0.01. Also PR changed from 40% before to 53% after and this value was significantly greater than the Non-Ac group (38%), p < 0.01. Conclusions: Significant increases in pregnancy outcomes were con- firmed by this study and the data uniquely supported the advantage of acupuncture in patients with normal PI (prior studies were done on patient with PI > 3). We also demonstrated that both acupuncture treatment protocols could be used together with a synergistic effect. Finally, this study is the first to demonstrate that the use of acupuncture in patients with poor prognoses (elevated Peak FSH, longer history of infertility, poor sperm morphology) can achieve similar pregnancy rates to normal prognosis patients.

Acupuncture and Good Prognosis IVF Patients: Synergy

P. C. Magarelli, D. K. Cridennda, M. Cohen. Reproductive Medicine & Fertility Center, Colorado Springs, CO; East Winds Acupuncture, Inc., Colorado Springs, CO.

FERTILITY AND STERILITY®, Proceedings from the 2004 ASRM meeting in Philadelphia

OBJECTIVE: To determine the role of electro stimulation acupuncture and traditional combined with auricular acupuncture on IVF outcomes in good prognosis patients.

DESIGN: Retrospective case controlled clinical study. Acupuncture Consortium for treatment standardization. Reproductive Endocrinology & Infertility IVF Private Practice and Traditional Chinese Medicine Acupuncture Clinics.

MATERIALS AND METHODS: One hundred fourteen infertile patients undergoing controlled ovarian hyperstimulation with gonadotropins and GnRH agonist and antagonist for IVF-ET (2001 to 2003) in private practice IVF clinic. Only IVF patients with normal Day 3 FSH, normal uterine artery pulsatility indices, sperm morphologies over 7% normal by Kruger Strict Criteria and good response to ovarian hyperstimulation protocols (i.e., E2 over 2000 pg/ml) were analyzed.Intervention (s): Electrostimulation acupuncture – reduction of Pulsatility Index (PI) of the uterine artery and Traditional combined with Auricular acupuncture – Pre/Post embryo transfer protocols were used alone or in combination and resultant pregnancy outcomes were measured after IVF treatments. Main Outcome Measure(s): Cycles were grouped according to those that received No Acupuncture (Non-Ac) and those that received either one or both acupuncture treatments (Ac). Comparisons were made between Acupuncture treated IVF patients and Non-Acupuncture treated IVF patients in clinical pregnancies, ongoing pregnancies and birth outcomes. The statistics used for this analysis included; Tests for normal distribution: chi-square test, Kolmogorov-Smirnov Test Unpaired T-tests Stepwise Multiple regression Variance ratio test (F-Test) One-Way analysis of variance (ANOVA) with Student-Newman- Keuls (SNK) test for pair wise comparison of subgroups.

RESULTS: Total IVF cases 114, 53 with Acupuncture (Ac) and 61 without Acupuncture (Non-Ac). Demographics, Infertility Diagnoses, and Treatment Protocols were statistically the same between both groups and by design, the following parameters were similar: Sperm Morphology; Peak Day 3 FSH; Average Pulsatility Index; Peak E2 at hCG; and Post hCG P4. These parameters earned the designation of Good Prognosis group. Preg- S80 Abstracts Vol. 82, Suppl. 2, September 2004 nancy rates (PR) and Miscarriage rates (SAB) were statistically improved at the p < 0.05 levels in those patients that received Acupuncture (51% v 36% PR and 8% v 20% SAB in the AC v Non-Ac groups). There were no ectopic pregnancies in the Ac group and 9% in the Non-Ac group, p < 0.008. Finally, Birth rates (BR) per cycle start and per pregnancy were significantly higher in the Ac group, with 23% more births/pregnancy significant at the p < 0.05 level.

CONCLUSION: The use of adjunctive therapies in IVF protocols is gaining popularity. In previously published data, Acupuncture was reserved for Poorer Prognosis patients and enhanced outcomes were observed. In this study, we demonstrated that Good Prognosis patients would also benefit from inclusion of published Acupuncture protocols. This is also the first publication of Birth outcome data in Acupuncture treated IVF patients. Acupuncture significantly increased birth outcomes; it significantly decreased ectopic pregnancies and miscarriage rates. These data uniquely support a definitive role of both Electrostimulation and Traditional combined with Auricular Acupuncture in IVF in Good Prognosis IVF patients. Supported by: None.

Acupuncture and In Vitro Fertilization: Does the Number of Treatments Impact Reproductive Outcomes?

D.K. Cridennda L.Ac.(1), P.C. Magarelli MD, Ph.D. (2) , and M. Cohen, MBA (2).
.(1), East Winds Acupuncture Colorado Springs, CO; (2) Reproductive Medicine & Fertility Center, Colorado Springs, CO

Objective: The purpose of this study was to determine the optimal number of acupuncture treatments that provide the patient with the best IVF outcomes, i.e., pregnancy.

Materials and Methods: Retrospective clinical study in private practice Acupuncture and IVF center. Data were compiled in a group of infertile patients (n = 216) who received acupuncture during their IVF treatment cycle between 2001 and 2005. Data were analyzed to determine the optimal number of Electrical Stimulation (e-Stim) acupuncture treatments (Stener-Victorin protocol) that would result in a clinical pregnancy. Two hundred sixteen patients over a 4 year period were included in this study. Based on our previous studies, we determined a significant improvement in IVF outcomes when patients were treated with Acupuncture (Ac). We utilized two protocols: Stener-Victorin et al 1996 (reported on uterine blood flow) and Paulus et al. 2002 protocol (reported on acupuncture given just before and just after embryo transfer). Patients received a combination of both protocols. This population was stratified into pregnant and non pregnant groups and then evaluated by Student T=test and Chi-Square analysis for age, FSH levels, weight, BMI and E-2 levels. The pregnant and non-pregnant groups were further subdivided into those that received or did not receive acupuncture and were analyzed by Chi-square analysis. Since all patients received acupuncture consisting of e-Stim, their distribution was analyzed utilizing Kaplan- Meier survival analysis for pregnancy and no pregnancy to determine the number of e-stimulation that would provide the greatest chance for pregnancy.

Results: Patients age, day 3 FSH levels, weight, BMI (body mass index) and E2 (estrogen level at embryo transfer) were not statistically significantly different between the Non Acupuncture (No Ac) and the Acupuncture (Ac) groups. There was a statistically significant improvement (p < 0.01) in pregnancy rates in the group that received Ac (49 patients of 106 (37.4%) in the No Ac became pregnant vs. 77 patients of 111 (61.1%) of the Ac group became pregnant). This is over 23% increase in pregnancy rates in the Ac group. When the data were compared between e-Stim treatments in the Ac only group, an average of 6.5 treatments were found in the non-pregnant Ac group and 5.9 treatments in pregnant Ac group (not statistically significantly different). When the data were plotted comparing pregnant vs. non pregnant Ac patients, there was a trend towards numerically more e-Stim treatments in those who achieved a pregnancy. In order to confirm or refute differences in these two groups, Kaplan Meier’s survival analyses were done. Based on these analyses, the average accumulated affect in the non pregnant Ac group was 5.1 e-Stim treatments and 8.4 e-Stim treatments in the pregnant Ac group. This was statistically significantly different at the p < 0.05.

Conclusion: In traditional Chinese medicine the basic theory is that only when the body is balanced will it function at its optimal level. Acupuncture helps restore balance which results in a higher chance of achieving pregnancy. In our study, we found that patients who received more than 8 e-Stim treatments appeared to have the maximum benefit for IVF outcomes: pregnancy (p < 0.05). In our study, we also reviewed the independent effects of the Paulus protocol, however due to small numbers; we could not perform the analyses. In the IVF center included in this study, patients receive Valium (diazepam) to reduce smooth muscle contractility. This treatment may provide all that is needed to reduce uterine contractility and therefore the additional impact of Ac at the pre and post transfer (Paulus protocol) may well be masked by the medication. More study of these and other treatments must be done. We are currently investigating the role of Ac in stress hormone circulating levels.

Source : No outside source of funding.

Acupuncture in IVF Linked to Lower Miscarriage and Ectopic Rates

Cridennda Magarelli
research Presented at ASRM 2007

PHILADELPHIA – Women who receive acupuncture during the stimulation phase of an in vitro fertilization cycle and again immediately after embryo transfer have a higher live-birth rate than do controls, according to the first acupuncture study with this end point.

“Other studies have looked at pregnancy rates, but what is really important is whether or not there is a baby,” said Paul C. Magarelli, M.D., who reported his findings at the annual meeting of the American Society for Reproductive Medicine.

The retrospective study included 131 women who were undergoing standard in vitro fertilization (IVF) or Intracytoplasmic sperm injection (ICSI). All of these women were considered good prognosis candidates for IVF/ICSI and were given the choice of having acupuncture.

A total of 83 women declined (controls) and 48 accepted.

There were no significant differences between the two groups in terms of infertility diagnoses, demographics, and treatment protocols, except that sperm morphology was slightly better in the partners of women receiving acupuncture (7.3% vs. 5.9 % normal forms with strict criteria evaluation), and the average uterine artery pulsatility index was lower in the acupuncture group (1.57 vs. 1.72), said Dr. Magarelli of the department of ob.gyn. at the University of New Mexico, Albuquerque.

The study found that pregnancy rates per embryo transfer were not significantly different between the two groups (50% in the acupuncture group and 45% in controls).

The miscarriage rate was almost halved in the acupuncture group (8% vs. 14%).

In addition, the rate of ectopic pregnancies was significantly lower in the acupuncture group-0 of 24 pregnancies (0%) vs. 2 of 37 pregnancies (9%), said Dr. Magarelli, who is also in private practice in Colorado Springs and Albuquerque.

Thus, the live-birth rate per IVF/ICSI cycle was significantly higher in the acupuncture group than in controls (21% vs. 16%).

“The live-birth rate per pregnancy is an even more telling number, since some cycles get cancelled. There was a 42% live-birth rate per pregnancy in the acupuncture group, compared to a 35% rate in the non acupuncture group,” Dr. Magarelli said in an interview with this newspaper.

“We believe that what we are doing is improving the uterine environment such that implantation is improved,” he added.

The study used two acupuncture protocols.

The Stener-Victorin electrostimulation protocol-which has been shown to reduce high uterine artery blood flow impedance, or pulsatility index (Hum. Reprod. 1996;11:1314-7)-was used for nine treatments during ovarian stimulation.

The second acupuncture technique-the Paulus protocol, which has been associated with improved pregnancy rates (Fertil. Steril. 2002;77:721-4)-was used within 24 hours before the embryo transfer and 1 hour after.

“This protocol has demonstrated reductions in uterine contractility, so by relaxing the uterus before the embryo transfer and immediately after, we felt we were setting up a better environment for implantation,” Dr. Magarelli said.