Treating Female Infertility and Improving IVF Pregnancy Rates With a Manual Physical Therapy Technique*

Belinda F. Wurn, PT; Lawrence J. Wurn, LMT; C. Richard King, MD; Marvin A. Heuer, MD; Amanda S. Roscow, MPT; Eugenia S. Scharf, PhD; Jonathan J. Shuster, PhD

Disclosures

Medscape General Medicine. 2004;6(2):51 

In This Article

Study II. Improving IVF Pregnancy Rates With a Manual Physical Therapy Technique

Several of our patients who had been receiving the treatment for abdominopelvic pain announced their intention to undergo IVF because they were unable (for various diagnosed causes) to achieve a natural pregnancy. Thus, in 1998, we began investigating the efficacy of site-specific soft-tissue therapy as an adjunct to ART for women with suspected or diagnosed pelvic adhesions.

Introduction

In the United States alone, the number of live birth deliveries per year resulting from all ART procedures has risen exponentially from 5600 in 1991,[25] to 14,573 in 1996, to 29,344 in 2001.[26] Of the 29,344 live birth deliveries, 21,813[27] were through the use of the woman's own (nondonor) fresh eggs or embryos, which accounts for 75.2% of all ART procedures.[28] [Note: A live birth delivery may include multiple babies.[26]]

For those unfamiliar with the process, the typical ART cycle using fresh nondonor eggs or embryos includes 4 prepregnancy steps. The cycle starts when the woman begins taking drugs to stimulate ovulation. If successful, the next step is egg retrieval. The eggs are combined with sperm and a few days after fertilization (if successful), selected embryo(s) are transferred into the uterus. This process is known as IVF and represents 99% of ART procedures.[27,29]

A sobering fact is that the 21,813 live births using fresh nondonor eggs represent only 27% of ART cycles started (80,864); 31.4% of egg retrievals (69,515); and 33.4% of embryo transfers (65,363).[27,30]

For ART data collection purposes, pregnancy is defined as a clinical rather than a chemical pregnancy.[31] Although a chemical pregnancy (positive pregnancy test) can be detected by a positive human chorionic gonadotropin within 5 days, a clinical pregnancy is one that has progressed to the stage where the gestational sac and fetal heart motion can be documented by ultrasound.[25,31]

Given that only 33.4% of embryo transfers result in a live birth, it is not surprising that a priori pregnancy success rates, expressed as pregnancy per cycle, retrieval, or transfer, are also disappointingly low. The 26,550 clinical pregnancies obtained by ART cycles using fresh nondonor eggs or embryos in 2001 represent 32.8% of the total ART cycles started (80,864); 38.2% of egg retrievals (69,515); and 40.6% of embryo transfers (65,363).[27,29]

Although other factors (ie, indication, number of transferred embryos) are involved, the age of the female is the primary determinant of IVF success at every stage of the ART process: the prognosis for women older than age 40 is considerably poorer than those who are younger.[25] For women in the 5 age groups, < 35; 35–37; 38–40; 41–42, and > 42, the calculated 2001 national rates of pregnancies per embryo transfer are, respectively: 48%; 42%; 34%; 24%; and 12%.[32] The corresponding rates for live births per transfer are: 41%; 35%; 25%; 14%; and 6%.[29,32]

Since live births per embryo transfer have been steadily improving (from 28% in 1996 to 33.4% in 2001),[33] an intervention that increases the frequency of clinical pregnancy rates, particularly in the older age groups, would automatically increase the frequency of live-birth deliveries.

Subjects

Selection. As in Study I, the primary criteria for inclusion in this prospective study were the inability to conceive following at least 12 months of unprotected intercourse and suspected or confirmed pelvic adhesions due to abdominal and/or pelvic surgery, infectious or inflammatory disease (eg, endometriosis, PID), miscarriage, or trauma within the abdominopelvic area. Other criteria were the following:

  • intention to undergo IVF therapy within 15 months of the last (manual physical therapy) treatment date;

  • decision to use fresh nondonor (own) embryos;

  • ability to progress to the embryo transfer stage of the ART procedure (see footnote).

Between September 1998 and January 2003, a total of 36 women received an individualized series of site-specific manual physical therapy treatments. Of these, 11 patients were ultimately omitted from the present study for the following reasons: 3 used frozen nondonor eggs; 2 used donor eggs; 2 did not progress to the embryo transfer stage (1 woman conceived naturally before then); and 4 others were lost to follow-up, leaving a total of 25 patients.

Gynecologic History. All 25 patients in this study had proven or clinically well-supported suspicion of adhesions. Medical diagnoses included:

 

Infectious/inflammatory disease (23) 92.0%
Abdominopelvic surgery (21) 84.0%
Abdominopelvic trauma (14) 56.0%
Confirmed pelvic adhesions (14) 56.0%
Endometriosis (9) 36.0%
Pelvic inflammatory disease (2) 8.0%

 

Before treatment, 14/25 patients reported a total of 21 prior natural pregnancies, only 4 of which resulted in a live birth. Twenty patients had a total of 78 prior ART attempts, including 54 IUIs. The total number of prior ART pregnancies was 3; 2 of these ended in miscarriage. Thus, before receiving the therapeutic intervention, there was only 1 prior ART full-term pregnancy in 78 attempts.

Characteristics. The 25 study participants comprised a multiethnic, primarily white, group, ranging in age from 28 to 44 years. At the time of embryo transfer, the mean age was 36 (median, 35.4), and the mean duration of infertility was 4.6 years (median, 3.5).

Procedures/Intervention

A total of 23/25 (92.0%) patients received the recommended minimum of 10 hours of treatment. [Note: As of January 2001, 10 hours was the required minimum.] None of the patients received concurrent infertility therapies during the treatment period.

Data Collection

Study patients were evaluated and treated between September 1998 and January 2003. Approximately 1 year after their last treatment date, patients were contacted to determine whether they had: (1) undergone the embryo transfer phase of IVF therapy, and (2) used fresh nondonor eggs/embryos (vs frozen or donor eggs).

The final data set includes 25 patients who underwent ≥1 IVF transfers within a maximum of 15 months following treatment, using fresh nondonor eggs/embryos. Patients who progressed from embryo transfer to pregnancy were tracked to anticipated delivery date, when possible.

In lieu of asking patients to serve as a control group for this as yet unproven adjunctive therapy, the decision was made to compare the study results with the vast, preexisting control groups 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).[26] The control group data set was extrapolated from the various figures in this report.

By law, the CDC reports its ART success rates by treatment cycles started each year, rather than per patient. In accordance with this convention, women who have started ≥ 2 cycles per year are represented more than once. Eight of the 25 women in the present study had 2 cycles each, for a total of 33 cycles. CDC success rates, in all age groups using fresh nondonor eggs/embryos, are somewhat (not significantly) lower for women who underwent a previously unsuccessful ART cycle.[34]

The CDC also reports its National Summary by age groups. Although other factors (eg, infertility cause, number of embryos transferred) should be considered, a woman's age (when using her own eggs) is the primary determinant of success at every stage of the IVF process.[25] Thus, we did not attempt to assess the effects of factors other than age in this study.

Statistical Methods

The main outcome measure--pregnancy/transfer rate (as well as the live birth/transfer rate)--was compared with the CDC 2001 rates (adjusted for age), as follows. For each attempt, the expected rate is the probability of pregnancy and live birth, respectively, for a woman of the identical age in years. CDC report Figure 13 (and its accompanying text)[32] provides these data. There is no material difference in success rates between an unsuccessful first attempt and subsequent ART attempts for the same woman.[34] Because of the small sample sizes, large sample approximations for the Mantel-Haenszel statistic[35] 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]

 

A 95% confidence interval for the odds ratio was obtained via 10,000 simulations, finding the odds ratios that make the P value .025 and .975.

Results

To assess the effectiveness of this site-specific manual soft-tissue therapy in improving pregnancy rates in women undergoing subsequent IVF, the main outcome measure was clinical pregnancy via the transfer of fresh embryos from nondonor eggs, within 15 months of the last (manual) treatment date.

As discussed above, this study included only those patients who had progressed beyond the early stages (egg production/retrieval and fertilization) of the ART cycle to the embryo transfer stage, and had used fresh nondonor eggs/embryos. Accordingly, the study results are compared with the 81% (n = 65,353) of the CDC cycles that reached the embryo transfer stage. These numbers were extrapolated from various figures in the 2001 report.[27,29,32,33]

As shown in Table 4 , for pregnancies, based on 33 transfers, there were 22 successes. The CDC age-adjusted expected rate was 12.7 successes; and the standard error in the observed rate is 2.7 (P < .001).

The estimated age-standardized pregnancy odds ratio of manual treatment pre-IVF to no pretreatment is 3.20 (95% confidence interval 1.55–8.4). As an example, if the odds of success for a control treatment is 1:2 vs the odds of success for an experimental treatment of 2:1, the odds ratio is 2.0/0.5 = 4.0. Note that equivalence corresponds to an odds ratio of 1.00, which is excluded from the pregnancy interval but not from the live birth interval (below).

The CDC pregnancy rates per age group ranged from 12% (age > 42) to 48% (age < 35). In comparison, the pre-IVF study pregnancy rates ranged from a low of 33% (age > 42) to more than 70% (age < 35).

Speaking in terms of actual patients, rather than embryo transfers, clinical pregnancies were documented in 19 of 25 women. The mean number of treatment hours was 17.1. There was no meaningful difference in treatment time between those who progressed from transfer to pregnancy (mean, 16.9 hours) and those who did not (mean, 17.5 hours).

Although the main outcome measure of this study was pregnancy within 15 months of the last (manual) treatment date, 15 of 33 transfers have resulted in live births or continuing pregnancies. As seen in Table 5 , the CDC age-adjusted expected number was 10.3, and the standard error for the observed rate was 2.6 (P = .065). Similarly, it can be estimated that the age-standardized successful live birth odds ratio of manual treatment pre-IVF to no treatment is 1.86 (95% confidence interval 0.86–4.3).

The confidence interval indicates that plausible outcomes range from a clinically insignificant disadvantage to a clinically important advantage for this pre-IVF treatment over common medical practice in terms of live births. Again, speaking in terms of actual patients, rather than embryo transfers, 15/25 women have already delivered (n = 13) or are still pregnant (n = 2).

Treatment Safety. None of the patients in the study reported any observable complications or adverse side effects as a result of their treatment; and all but 1 patient who presented with pain at the initial evaluation reported decreased pain during or after treatment.

Discussion

Although we can infer that the entire confidence interval for the pregnancy odds ratio is clinically significant, the confidence interval for live births contains both clinically insignificant values (eg, near 1.0), as well as clinically significant values. However, the confidence interval for the odds ratio demonstrates the potential for anything from a slightly lower rate to a much higher rate. As can be seen in Table 4 and Table 5 , the results were particularly encouraging for women > 40 years of age. Thus, further research with a larger sample is needed to define the successful live birth confidence interval more precisely.

Nevertheless, because national live births/transfer rates have been steadily improving (from 28.0% in 1996 to 33.4% in 2001),[33] an intervention that obviously increases clinical pregnancy rates should increase live birth delivery rates for patients undergoing IVF embryo transfers.

Related Research. In terms of the efficacy of alternative therapies as pre-IVF aids, there is 1 published, randomized controlled trial of the effect of acupuncture on the pregnancy rate of women undergoing IVF or intracytoplasmic sperm injection. The 160 patients (mean age, 32.5) in this German study were randomly assigned to the acupuncture or control group. The main outcome measure was clinical pregnancy. Analysis showed that the average pregnancy rate for the acupuncture group was 42.5% (34/80) vs 26.3% (21/80) for the control group (P = .03).[36] Investigators have concluded that further studies are warranted.[37,38] The acupuncture results can be compared with the average 66.7% (22/33) pregnancy rate obtained in the present study, which used the [much higher] 2001 CDC average pregnancy/transfer rate of 40.6% as the control group (P < .001). [Also see Future research, below.]

Future Research. As with Study I, the encouraging results warrant the replication of Study II, using a considerably larger sample of women (particularly in the age 35+ groups) randomized into experimental (treatment) and control (no treatment) groups. A second control group, composed of infertile women lacking strong indications of adhesion formation, would permit testing the hypothesis that this specific therapy might also benefit infertile women without adhesions, eg, by improving circulation in the pelvic region. The results of this arm of the study could be compared with acupuncture, which seems to work (in part) by increasing blood flow to the uterus.[37]

Comments

3090D553-9492-4563-8681-AD288FA52ACE
Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as:

processing....