Medical Studies

Pilot Study: Reducing IVF Failure Rates with a Manual Physical Therapy Technique*

The following is a non-published study of our "most challenging" IVF cases. Non-published studies are appropriate with smaller study groups. This study had limited enrollment, since we only accepted patients who had failed two or more IVF transfers, then came to us before attempting another transfer. Although we were limited in the number of participants, we included every patient we had who fit the criteria. The results of this study were very promising and exciting.

Criteria for acceptance: we accepted only those patients who had

failed to become pregnant with every IVF transfer they had ever attempted, and
not had any pregnancy in at least two prior IVF transfers.

After therapy, these same women (who had failed so many prior attempts) achieved a 71% clinical pregnancy rate and a 57% live birth rate with their first post-treatment IVF.

As a non-published study, we are able to include the abstract and entire text of the study below.

ABSTRACT

Belinda F. Wurn, PT; Lawrence J. Wurn, LMT; C. Richard King, MD; Marvin Heuer. MD; Amanda S. Roscow, MPT; Eugenia S. Scharf, PhD; Jonathan J. Shuster, PhD
© Clear Passage Therapies, Inc. July, 2005

Objective: To assess the effectiveness of a site-specific manual soft-tissue therapy in improving in vitro fertilization (IVF) pregnancy rates in women who failed to become pregnant via two or more prior IVF embryo transfers.

Design and Intervention: Based on a previous study in which clinical pregnancies were documented in 19 of 25 (76%) women who underwent IVF following a specific manual therapy, a data subset of 7 patients was selected for further analysis. These 7 patients met the additional criterion of failure to ever become pregnant via (2 or more) IVF embryo transfers, prior to therapy. Treatments were designed to improve biomechanical function of the reproductive organs and adjacent structures by restoring visceral, osseous, and soft-tissue mobility.

Main Outcome Measure: Clinical pregnancy on the first post-treatment IVF embryo transfer.

Results: Of this subset of “challenging” patients (median age, 35.1), clinical pregnancies were documented in 5 of 7 women vs. the US Centers for Disease Control and Prevention (CDC) age-adjusted estimate of 2.1. The estimated odds ratio for a successful pregnancy in a cycle (manual treatment vs. no treatment) is 5.8 (P = .025, 2-sided).

Conclusions: Since 71.4% of these previously unsuccessful patients became pregnant on their first post-treatment IVF and 57% had full-term births, it appears that this nonsurgical, noninvasive manual soft-tissue therapy facilitates fertility in "challenging" IVF patients. With no risks and few, if any, complications or adverse effects, it should be considered as an adjunct to current infertility treatments.

* Wurn Technique®, patent pending

INTRODUCTION

This small follow-up/pilot study was prompted by the discovery that prior to receiving manual therapy, many of our patients had experienced a variety of assisted reproductive technology (ART) failures, including surgical/in vitro fertilization (IVF) attempts.[1]

Although the previous study demonstrated the effectiveness of this manual therapy vs. no therapy in increasing IVF pregnancy rates (P <.001),[1] 14 of the 25 patients had not previously undergone IVF, and others had reported a prior ART pregnancy. In order to evaluate the efficacy of the therapy in treating women with an individual history of past IVF failures, a data subset of the most “challenging” patients was selected for further analysis. The operational definition of “challenging” was the failure to ever become pregnant via (2 or more) IVF embryo transfers.

According to the 2001 Assisted Reproductive Technology Success Rates: National Summary and Fertility Clinic Reports, published by the Centers for Disease Control and Prevention (CDC) and the American Society for Reproductive Medicine (December 2003),[2] the 26,550 clinical pregnancies obtained by ART cycles using fresh nondonor eggs (the most common type) represent only 32.8% of the total ART cycles started and 40.6% of embryo transfers.[3,4]

Since national live births/transfer rates have been steadily increasing (from 28.0% in 1996 to 33.4% in 2001),[5] an intervention that improves IVF pregnancy rates will automatically result in increased delivery rates.

Adhesions and Infertility
Of the approximately 5 million infertile women in the United States, 2 million (40%) have mechanical (as opposed to medical/hormonal or idiopathic) infertility;[6] one primary cause of mechanical infertility is the formation of pelvic adhesions.[7,8]

Briefly, adhesions and microadhesions are deposits of fibrous (scar) tissue that form as a natural response to tissue injury caused by infection, inflammation, surgery, or trauma. Although they form as a by-product of the healing process, they may remain long after the original injury site has healed. Adhesions have the potential to bind organs and muscles to other structures, thereby distorting the anatomy and causing decreased mobility and function.[7]

The formation of pelvic adhesions is a common outcome of pelvic surgery, infection, inflammation, and trauma. Adhesions are also known to accompany related conditions such as chronic abdominal pain, bowel obstruction, polyps, pelvic spasms, pelvic inflammatory disease, tubal obstruction, and endometriosis.[8-10] It is presumed that the relationship is a causal one; i.e., these dysfunctions cause or are caused by adhesions.

Because abdominopelvic adhesions can restrict the mobility and function of the organs, muscles, ligaments, osseous structures, nerves and fascia, they can affect the biomechanics of the entire abdominopelvic region. In doing so, they reduce the ability to become pregnant, even with IVF and other ART procedures. Infertility-causing adhesions, for example, may form on the uterine walls and ligaments thereby increasing the possibility of implantation problems, uterine spasm, and miscarriage. Adhesions may also form at and within the cervical tissues, creating stenosis, and contributing to uterine and cervical spasms.[1]

[Note: See Wurn et al.[1] for a detailed discussion of connective tissue and adhesions and the specific effects of abdominopelvic adhesions.]

Value of Intervention
Clinical observation over many years has demonstrated that site-specific manual soft-tissue therapy improves elasticity, distensibility, and soft-tissue mobility. Theoretically, soft-tissue mobilization may break down the collagenous cross-links and adhesions that cause pain and dysfunction,[11] including dyspareunia and physician-diagnosed infertility.[1,12]

In addition to its efficacy as a natural infertility treatment, the therapy apparently works as a pre-IVF adjunct to regular gynecologic care.[1] We presume that it improves mobility and motility of the reproductive organs by decreasing one of more of the following:

adhesions and microadhesions on, within, and external to the uterine walls, thus helping to create a more hospitable surface for embryo implantation;
cervical spasm, uterine spasm, and hypertonicity, thus creating a more relaxed environment for embryo implantation;
cervical adhesions, tension, and stenosis within the cervix and its attachments, thus improving cervical mobility and expediting transfer to the preferred implantation site.
adhesions and microadhesions attached to the uterine ligaments (e.g., broad, round, uterosacral, uterovesical, parametrium, ovarian, mesosalpinx), thus improving uterine mobility and function.

METHODOLOGY

Subjects

Selection. The patients in this analysis represent a subset of the 25 subjects in a previous pre-IVF study.[1] The primary criteria for inclusion in that study were the inability to become pregnant within a minimum of 12 months of unprotected sexual intercourse and a history of confirmed or suspected adhesions due to abdominal and/or pelvic surgery, infectious or inflammatory disease (e.g., endometriosis, PID), miscarriage, or trauma within the abdominopelvic area.

Secondary criteria were the intent to undergo IVF within 15 months of the last (manual physical therapy) treatment date, the ability to progress to the embryo transfer stage of the IVF procedure, and the decision to use fresh nondonor (i.e., their own) embryos. The 15 month interval was purposely chosen since many patients in the study wished to give themselves a year to conceive naturally before trying IVF. We allowed 3 extra months to enable them to plan and complete the pre-transfer (fertility drugs, egg retrieval, etc.) phases of the ART cycle.

The additional criterion for inclusion in the present data analysis was the failure to ever become pregnant via 2 or more successive (pre-therapy) IVF transfers, including their initial attempt. All 7 women in this pilot study experienced at least two prior IVF failures; 3 of the 7 also failed to have a pregnancy on their third (pre-therapy) attempt.

Gynecologic history. As in the previous study, the patients in this data subset had either proven or clinically well-supported suspicion of abdominopelvic adhesions. Medical diagnoses included the following: abdominopelvic surgery (7/7); infectious/inflammatory disease (6/7); abdominopelvic trauma (4/7); and confirmed pelvic adhesions (4/7).

Characteristics. The patients ranged in age from 30 to 44. At the time of the post-treatment embryo transfer, the mean age was 34.9 (median, 35.1). The mean duration of infertility was 5.8 years (median, 4.7). Five patients had never had a natural pregnancy; the other two had been infertile for 2.5 years and 7 years, respectively, prior to receiving the manual therapy.

Procedures/Intervention
The treatment, a unique protocol of soft-tissue physical therapy, has been described in an earlier study.[1] In compliance with the standards of the American Physical Therapy Association,[13] detailed clinical records were kept of each patient’s treatment sessions, including dates, duration, areas treated, techniques performed, and symptomatic complaints. The mean number of treatment hours was 14.7 (median, 15). None of the patients received concurrent infertility therapies during the manual physical therapy treatment period.

Data Collection
To evaluate the efficacy of this site-specific manual soft-tissue therapy in improving IVF clinical pregnancy rates in women with a history of IVF failures, the main outcome measure was clinical pregnancy via the first post-treatment transfer of embryos from fresh, nondonor eggs within 15 months of the last manual therapy session.

The patients were evaluated and treated between September 1998 and June 2002. About 1 year after their last treatment date, all were contacted to ascertain if they had yet undergone the embryo transfer phase of the IVF procedure and, if so, used fresh nondonor eggs/embryos (vs. frozen or donor eggs).

The final data subset includes 7 patients who underwent IVF transfers within 15 months following the manual therapy (mean = 3.7 months; median, 3 months). Patients who progressed from embryo transfer to pregnancy were tracked to expected delivery date and beyond, when possible.

As in the previous study,[1] the data subset results were compared with the preexisting control group represented by the 2001 Assisted Reproductive Technology Success Rates: National Summary and Fertility Clinic Reports, released by the Centers for Disease Control and Prevention (CDC) and the American Society for Reproductive Medicine (December 2003).[2] The control group data set was extrapolated from several Figures[14-16] in this report.

Although other factors (e.g., infertility cause, number of transferred embryos, etc.) might be relevant, age is considered the primary determinant of success at every stage of the IVF process.[17] Thus, no attempt was made to examine other variables in this pilot study.

Statistical Methods
The main outcome measure, pregnancy/transfer rate (along with the live birth/transfer rate), was compared with the CDC 2001 rates (adjusted for age) as follows. The expected rate for each attempt is the probability of pregnancy and live birth (respectively) for a woman in the identical age group. The CDC report Figures 20 and 21 (and accompanying text) provide the live birth rates for ART cycles using fresh nondonor eggs or embryos, by women’s age and history of previous ART cycles among women with (1) no previous births, and (2) one or more previous births.[15,16]

The CDC reports that “previous ART cycles may be related to the success of the current ART cycle.” Whereas success rates were slightly lower (5.9% to 1.2%) for women in all age groups who had had no previous births, there was no decline for those who had given birth in the past as a result of natural conception or ART.[15,16] Six of the 7 patients in this study had no previous births; 1 patient reported a prior natural pregnancy and delivery.

[Note: Although the CDC does not report the number of cases represented in Figures 20 and 21,[15,16] the approximate number of embryo transfers using fresh, nondonor eggs was 65,000; Figure 19[18] states that 46.6% of these reported having undergone a previous cycle. Thus, the control group sample is very large indeed.]

Since the CDC does not report pregnancy rates by history of previous ART cycles, these data were extrapolated from Figure 7,[14] which shows that 82.2% of ART pregnancies using fresh nondonor eggs or embryos resulted in a live birth.

Due to the small sample size in this pilot study, large sample approximation for the Mantel-Haenszel statistic[19] were thought to be unreliable, and 10,000 simulations were used to obtain the 2-sided P value.

Odds ratios were estimated by the following formula, with N = Sample Size, OBS = Observed Total, and EXP = Expected Total based on the CDC 2001 data:

Estimated Odds Ratio = OBS(N-EXP)/[(N-OBS)EXP]

RESULTS

Numerous studies over the years have unequivocally demonstrated the statistically significant decline in female fertility with age. Since at least one expert claims age 35 is a “watershed”[7] for reproductive probability and since the CDC uses “below 35” as its first age bracket, Tables 1 and 2 show the pregnancy and live birth rates obtained by patients in <35 and 35+ age groups. For the <35 age group, the first post-treatment IVF produced pregnancies and subsequent deliveries in 66.7% (2/3) of the patients. For the 35+ age groups, the post-therapy IVF rates were 75.0% (3/4) pregnancy and 50% (2/4) live birth delivery. The total pregnancy and live birth delivery rates were 71.4% (5/7) and 57.1% (4/7), respectively.

Table 1 shows the pregnancy results in comparison to the CDC age-adjusted rates. The observed pregnancy rate of 5 (of 7) successes can be compared to the CDC expected rate of 2.1 (of 7) (P = .025, 2-sided). The estimated age-standardized pregnancy odds ratio of pre-IVF manual treatment to no pretreatment is 5.8. (Equivalence corresponds to an odds ratio of 1.0). There was no meaningful difference in treatment time between the patients who became pregnant (mean, 13.6 hours) and those who did not (mean, 17.5 hours).

Table 1: Observed vs. Expected Pregnancies
Pregnancies
Age	Transfers	Observed	CDC 2001 Rate	Expected
< 35	3	2 (67%	36.9%	1.11
35-37	3	2 (67%)	31.0%	0.93
>42	1	1 (100%)	6.2%	0.06
Total	7	5		2.10

Estimated odds ratio = 5.8 (P = .025, 2-sided)
Observed = rate for manual pre-IVF data subset (current study)
Expected = projected from CDC Figures 7, 20, 21[14-16]
(Expected = Transfers multiplied by the CDC 2001 rate)

Although the main outcome measure in this follow-up pilot test was pregnancy, 57.1% of the 7 embryo transfers resulted in live births. As can be seen in Table 2, the observed live birth rate of 4 (of 7) successes can be compared to the CDC expected rate of 1.7 (of 7) (P = .062, 2-sided). The estimated age-standardized live births odds ratio of pre-IVF manual treatment to no pretreatment is 4.1. (Again, equivalence corresponds to an odds ratio of 1.0.)

Table 2. Observed vs. Expected Live Births
Live Births
Age	Transfers	Observed	CDC 2001 Rate	Expected
< 35	3	2 (67%)	30.3%	0.91
35-37	3	1 (33%)	25.5%	.76
>42	1	1 (100%)	5.1%	0.05
Total	7	4		1.72

Estimated odds ratio = 4.1 (P = .062, 2-sided)
Observed = rate for manual pre-IVF data subset (current study)
Expected = projected from CDC Figures 20, 21[15,16]
(Expected = Transfers multiplied by the CDC 2001 rate)

In brief, 80% (4/5) pregnancies resulted in a live birth, a figure comparable to the 82.2% rate reported by the CDC for ART cycles using fresh nondonor eggs or embryos.[14]

Since this therapy has also been shown to be effective in facilitating natural fertility, it is worth noting that one 36-year old patient who failed to become pregnant via three pre-treatments IVFs, as well as the post-treatment IVF, conceived naturally within the 15 month limit, and subsequently had a live birth. Another patient who did have a successful post-treatment pregnancy and live birth also achieved a subsequent natural pregnancy, but later miscarried.

Treatment safety. As in the previous study,[1] none of the patients in this data subset reported any observable complications or adverse side effects as a result of therapy.

DISCUSSION

Although the previous study[1] had demonstrated the effectiveness of the pre-IVF manual therapy (compared to no therapy), 14 of the 25 patients had not undergone any prior IVFs, and others had reported prior ART pregnancies. In an attempt to assess the specific value of the therapy in reducing individual IVF failure, a data subset of 7 “challenging” patients was selected for further analysis. Although none of these patients had become pregnant via (multiple) pre-treatment IVFs, 5 of the 7 (71.4%) had a pregnancy on their first IVF following manual therapy.

Apparently, this site-specific manual soft-tissue intervention facilitates embryo implantation by improving the mobility and motility of the reproductive organs. (See “Value of Intervention” above.)

Because national live births/transfer rates have been continuously rising (from 28.0% in 1996 to 33.4% in 2001),[5] an intervention that increases pregnancy rates in refractory conditions should result in increased live birth delivery rates.

Future research: Obviously, the results of this “follow-up pilot study” need to be replicated using a considerably larger sample of patients, randomized into experimental (treatment) and control (no treatment) groups. Although it is difficult to convince women (especially those age 35 and above) to delay therapy in the interests of science, a large subject pool would enable analysis of factors other than age (e.g., number of embryos, etc.) Since the mean elapsed time between last treatment date and IVF embryo transfer was only 3.7 months for this subset of patients, selection criteria could include intention/ability to undergo IVF embryo transfer within 3-6 months, which would shorten the “delay” and follow-up period considerably.

Given the hypothesis that the treatment works by breaking down abdominopelvic adhesions and microadhesions, visible evidence of their presence in all patients would definitely support confirmed or clinical suspicions. Thus, another selection criterion might be imaging, such as ultrasound Doppler.

CONCLUSION

The data trend across the previous and present studies increasingly supports the hypothesis that this distinctive, noninvasive, nonsurgical protocol of manual soft-tissue therapy (with little risk, adverse side effects, or complications) seems to be an effective means of improving subsequent IVF pregnancy rates. Since few women are emotionally or financially able to handle multiple IVF failures, the therapy should be considered as an adjunct to current medical infertility treatments. The major indication for its use is a history indicating abdominopelvic adhesions; i.e., infection, inflammation, prior surgery, or trauma at the reproductive organs or neighboring structures.

REFERENCES

Wurn BF, Wurn LJ, King CR, Heuer MA, Roscow AS, Scharf ES, Shuster JJ. Treating female infertility and improving IVF pregnancy rates with a manual physical therapy technique. Medscape General Medicine, June 18, 6(2), 2004. Available at http://www.medscape.com/viewarticle/480429.
2001 Assisted Reproductive Technology Success Rates: National Summary and Fertility Clinic Reports. Atlanta: Centers for Disease Control and Prevention and the American Society for Reproductive Medicine, 2003.
Ibid., Fig. 3, p. 15.
Ibid., National Summary, p. 71.
Ibid., Fig. 41, p. 53.
Stephen EH. Projections of impaired fecundity among women in the United States: 1995 to 2020. Fertil Steril 1996; 66:205–9.
Strickler RC. Factors influencing fertility. In: Keye WR, Chang RJ, Rebar RW, Soules MR, eds. Infertility: Evaluation and Treatment. Philadelphia: W.B. Saunders, 1995:8–18.
Drollette CM, Badawy SZ. Pathophysiology of pelvic adhesions. Modern trends in preventing infertility. J Reprod Med 1992;37:107–22.
Stone K. Adhesions in gynecologic surgery. Curr Opin Obstet Gynecol 1993; 5:322–7.
Steege JF, Stout AL. Resolution of chronic pelvic pain after laparoscopic lysis of adhesions. Am J Gynecol 1991;165:278–83.
Threlkeld AJ. The effects of manual therapy on connective tissue. Phys Ther 1992;72:893–902.
Wurn LJ, Wurn BF, King CR, Roscow AS, Scharf ES, Shuster JJ. Increasing orgasm and decreasing dyspareunia by a manual physical therapy technique. Medscape General Medicine. 2004; 6 (4). Available at http://www.medscape.com/viewarticle/493989.
American Physical Therapy Assn. Guide to Physical Therapist Practice, 1st ed. Alexandria VA: APTA. 1997:Appendix 7-2–7-3.
2001 Assisted Reproductive Technology Success Rates…[Ref. 2 above], Fig. 7, p.19.
Ibid., Fig. 20, p. 32.
Ibid., Fig. 21, p. 33.
Davis OK, Rosenwaks Z. In Vitro Fertilization. In: Keye WR, Chang RJ, Rebar RW, Soules MR, eds. Infertility: Evaluation and Treatment. Philadelphia: W.B. Saunders, 1995: 759–71.
2001 Assisted Reproductive Technology Success Rates…[Ref. 2 above], Fig. 19, p.31.
Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22:719-748. Abstract.

ACKNOWLEDGEMENTS

We would like to thank Marvin H. Heuer, MD and Joel Batzofin, MD for their encouragement in this series of research studies. We would also like to thank Kimberley Hornberger, PTA and editor Amy Burnette for their increasingly valuable contributions to our studies..