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ORIGINAL RESEARCH

Outcomes From Treatment of Infertility With

Natural Procreative Technology in an Irish General

Practice

Joseph B. Stanford, MD, MSPH, Tracey A. Parnell, MD, and Phil C. Boyle, MB

Objectives: We evaluated outcomes in couples treated for infertility with natural procreative technology

(NaProTechnology, NPT), a systematic medical approach for optimizing physiologic conditions for con-

ception in vivo, from an Irish general practice.

Methods: All couples receiving treatment from 2 NPT-trained family physicians between February

1998 and January 2002 were studied. The main outcome was live birth, and secondary outcomes in-

cluded conceptions and multiple births. Crude proportions and adjusted life-table proportions were

calculated per 100 couples.

Results: A total of 1239 couples had an initial consult for NPT, of which 1072 had been trying for at

least a year to conceive and initiated treatment. The average female age was 35.8 years, the mean dura-

tion of attempting to conceive was 5.6 years, 24% had a prior birth, and 33% had previously attempted

treatment with assisted reproductive technology (ART). All couples were taught to identify the fertile

days of the menstrual cycle with the Creighton Model FertilityCare System, and most received additional

medical treatment, including clomiphene (75%). In life-table analysis, the cumulative proportion of ﬁrst

live births for those completing up to 24 months of NPT treatment was 52.8 per 100 couples. The crude

proportion was 25.5. Younger couples and couples without previous ART attempts had higher rates of

live birth. Among live births, there were 4.6% twin births.

Conclusion: NPT provided by trained general practitioners had live birth rates comparable to cohort

studies of more invasive treatments, including ART. Further studies are warranted to compare NPT di-

rectly to other treatments. (J Am Board Fam Med 2008;21:375–384.)

Infertility is a common problem; one in every 7

couples hoping to have a baby experiences difﬁcul-

ties achieving or maintaining pregnancy serious

enough to seek medical intervention. 1 Infertility is

a chronic problem that involves both women and

men, has major psychosocial ramiﬁcations, and

usually requires addressing multiple issues, includ-

ing comorbid medical conditions and lifestyle, all

key elements of primary care practice. However,

treatments for infertility are largely provided by

physicians trained in subspecialties, including arti-

ﬁcial insemination, ovulation induction, and hor-

monal support of the menstrual cycle. 1,2 The in-

creasing shift of treatment toward assisted

reproductive technologies (ART), including in

vitro fertilization and intracytoplasmic sperm injec-

tion, has removed infertility treatment further from

the realm of the generalist or family physician. 1,3

ART is expensive, invasive, and involves some

risk to women. These include risks of the medical

and surgical procedures to retrieve oocytes, 4 in-

cluding ovarian hyperstimulation syndrome. 5

There are also concerns about short- and long-

term outcomes for the offspring. 6–9 The most

prominent concerns relate to the incidence of mul-

tiple pregnancies with ART treatment and the sub-

This article was externally peer reviewed.

Submitted 30 October 2007; revised 11 April 2008; ac-

cepted 15 April 2008.

From the Department of Family and Preventive Medi-

cine, University of Utah, Salt Lake City (JBS); the Depart-

ment of Family Medicine, University of British Columbia,

Vancouver, Canada (TAP); the Galway Clinic, Ireland

(PCB); and the International Institute of Restorative Repro-

ductive Medicine, London, United Kingdom (JBS, TAP,

PCB).

Funding: none.

Prior presentation: Portions of this work have been pre-

sented at the North American Primary Care Research Con-

ference, Vancouver, Canada, 21 October 2007.

Conﬂict of interest: none declared.

Corresponding author: Dr. Joseph B. Stanford, MD,

MSPH, University of Utah, Department of Family and

Preventive Medicine, 375 Chipeta Way, Suite A, Salt Lake

City, UT 84108 (E-mail: joseph.stanford@utah.edu).

doi: 10.3122/jabfm.2008.05.070239

Treatment of Infertility with Natural Procreative Technology 375

sequent perinatal complications, including low

birth weight and prematurity. 10 –12 Increasing the

availability of integrated primary methods for in-

fertility treatment that can be effectively provided

by a trained generalist physician with low risk to

women and offspring would potentially improve

access to care for couples dealing with infertility.

Natural procreative technology (NaProTech-

nology, NPT) is an integrated and systematic ap-

proach to infertility that is suitable for primary care

settings. It is based on a detailed study of events

that occur during ovulation and throughout the

menstrual cycle. 13,14 Abnormalities of the repro-

ductive cycle are identiﬁed and corrected to the

extent possible. 15–18 Patients receive thorough ed-

ucation about their fertility and are taught to mon-

itor biomarkers of their own fertility cycles. In the

process, they become equal partners in their own

evaluation and treatment.

A standardized NPT investigation usually re-

sults in the diagnosis of one or more abnormalities

of reproductive function that are associated with

infertility. Abnormalities commonly identiﬁed in-

clude decreased production of estrogenic cervical

mucus, intermenstrual bleeding or spotting, short

or variable luteal phases, and suboptimal levels of

the ovarian hormones estrogen and progesterone. 19

The physician trained in NPT then determines a

course of treatment that aims to correct the under-

lying abnormality, with the goal of optimizing

physiologic conditions for conception in vivo.

Common interventions include induction or stim-

ulation of ovulation 20 ; medications to enhance cer-

vical mucus production, including vitamin B6,

guaifenesin, or one of several antibiotics 21,22 ; and

hormonal supplementation in the luteal phase. 23

Doses of all medications are adjusted according to

the response of biomarkers and serum levels of

estrogen and progesterone measured in the midlu-

teal phase. 13,17 Concurrently, couples use their

awareness of ovulation biomarkers to time acts of

intercourse to maximize chances of conception. 24

Ongoing evaluation and support during pregnancy

often includes supplementation with human-iden-

tical progesterone, based on periodic measurement

of progesterone levels, in an effort to reduce the

risk of adverse pregnancy outcomes. 25–28

Outcomes for NPT have been published previ-

ously for a cohort of infertility patients in a spe-

cialty practice at its place of development (Creigh-

ton University). 29 This study was undertaken to

assess the outcomes of NPT as applied by trained

generalist physicians in Galway, Ireland. Although

NPT has been developed with both medical and

surgical protocols, this study evaluates the medical

protocols. We focused on the clinically relevant

outcomes of live birth and multiple births.

Methods

During the study period, the clinic was a single

physician ofﬁce, with the exception of January 2000

to August 2001, when a second physician was prac-

ticing in the same ofﬁce. The 2 physicians were

licensed family physicians in Ireland who had re-

ceived additional training in NPT through Creigh-

ton University (Omaha, Nebraska) and had suc-

cessfully passed all evaluations and examinations of

the NPT continuing medical education course.

The clinic primarily focuses on providing women’s

health services.

Data for the NPT treatment cohort were col-

lected from patients during their initial assessment

visit and at subsequent follow-up visits and re-

corded in the routine medical record for the prac-

tice. Data from routine follow-up telephone con-

tacts were also included in the medical records.

The relevant data for this study were abstracted

from medical records and entered into a comput-

erized database, with manual veriﬁcation of all en-

tered data.

Patients were primarily self-referred couples ex-

periencing difﬁculty conceiving and achieving a live

birth. All patients from Ireland who presented be-

tween February 1998 and January 2002 (inclusive)

and who proceeded beyond the initial explanatory

consultation were eligible for inclusion in this

study. Patients who had previously attempted ART

(including in vitro fertilization and intracytoplas-

mic sperm injection) were also included. A few

patients were advised after the initial consultation

that they were not eligible for NPT, mostly be-

cause of azoospermia or menopause; these patients

were not included in this analysis. We also excluded

patients that had been trying for less than a year or

who did not continue with the evaluation that was

recommended at the initial consultation.

The NPT infertility treatment implemented in

this clinic is a systematic multilevel investigation

and treatment program. 13 It begins with an initial

consultation in which reproductive physiology and

the various stages of NPT investigation and treat-

376

JABFM

September–October 2008 Vol. 21 No. 5

http://www.jabfm.org

ment are explained in detail to patients. They next

learn specialized fertility tracking of daily observa-

tions of vaginal discharge biomarkers (bleeding and

cervical ﬂuid), according to the Creighton Model

FertilityCare System. 15,16,30 After patients gained

competence in fertility tracking (no earlier than the

second month), timed blood samples were taken

with respect to the estimated time of ovulation as

prospectively identiﬁed by the woman’s own fertil-

ity chart. 13,31 Reproductive hormones, including

estradiol and progesterone, were measured and in-

terpreted in the context of the woman’s fertility

tracking chart. Medications to correct identiﬁed

hormonal abnormalities were prescribed after the

completion of these investigations, usually in the

fourth month. The goal was to optimize physio-

logic conditions for natural conception in each

menstrual cycle, including mucus discharge quality,

luteal hormone levels, ovulation, and the timing of

intercourse. It often takes several cycles of treat-

ment to reach optimal physiologic conditions.

Once reached, there may still be some suboptimal

cycles mixed with the optimal ones; for example, a

cycle where intercourse does not occur during the

fertile time. In addition, some patients conceive

and subsequently experience a spontaneous abor-

tion, after which they continue in the treatment

program. Patients were advised that a total of up to

24 months may be required to complete an ade-

quate trial of NPT to achieve pregnancy leading to

a live birth. Evaluation and treatment of the male

partner also took place during this time, as indi-

cated. Hormonal assessment and support contin-

ued through pregnancy, as indicated. 25 Although

specialized NPT surgical treatment may also form

part of the NPT program, it was not available in

this clinic in this time frame. A more detailed dis-

cussion of the NPT approach to infertility is avail-

able elsewhere. 13,19,32

Per-cycle pregnancy rates are not an appropriate

outcome to assess for NPT because of the longitu-

dinal and incremental nature of the NPT treatment

program. 33,34 Therefore, we chose a cohort ap-

proach with the couple, rather than the cycle, as the

unit of analysis. The main analyses for this study

were the cumulative proportion of couples experi-

encing a ﬁrst live birth during discrete time periods

after the beginning of treatment. For comparability

with other reports of infertility outcomes, we as-

signed the time of this outcome as the time of

conception leading to ﬁrst live birth. 35 Secondarily,

we also analyzed the cumulative proportion of ﬁrst

conceptions and cumulative proportion of with-

drawals. Life-table analysis was used to adjust for

couples withdrawing from treatment, or that com-

pleted 24 months of NPT treatment without preg-

nancy. Among the live births, we analyzed the pro-

portion of multiple births. Secondarily, we

analyzed the proportion with low birth weight and

prematurity.

The study protocol was reviewed and approved

by the Linacre Centre for Health care Ethics in

London, and the Institutional Review Board for

Human Subjects at the University of Utah. Because

data were abstracted from usual clinical data

sources and patient anonymity was maintained,

there was no requirement for written informed

consent of participants.

Results

A total of 1239 couples obtained an initial consult

for NPT during the study period. Of these, 167

couples were excluded because they had tried for

less than a year to conceive or because they did not

continue evaluation beyond the initial consultation.

The ﬁnal study cohort consisted of 1072 couples

that began treatment between February 1998 and

January 2002 (inclusive), with subsequent outcomes

followed through February 1, 2008. The women

were, on average, 35.8 years old (range, 25 to 48

years), and nearly all were white. One third (33%)

had previously attempted ART treatment. The

mean length of time that couples had attempted to

conceive before NPT treatment was 5.6 years

(range, 1 to 20 years). Approximately one fourth

(24%) of couples had a previous live birth. As

shown in Table 1, the 364 couples who ultimately

conceived with NPT treatment were slightly

younger (mean age, 34.8 years); had not been at-

tempting conception as long (mean duration, 4.8

years); were likely to have had a previous birth

(30%); and less likely to have attempted ART treat-

ment (21%).

In addition to teaching women to track their

fertility biomarkers with the Creighton Model in-

struction, the most common diagnoses given to

couples before and after NPT evaluation are shown

in Table 2. Through NPT evaluation, more than

half of the couples had suboptimal serum levels of

progesterone and estradiol during the luteal phase.

Approximately one fourth had limited cervical mu-

cus and 10% had polycystic ovarian syndrome.

doi: 10.3122/jabfm.2008.05.070239

Treatment of Infertility with Natural Procreative Technology 377

Table 1. Characteristics of Couples Beginning Treatment with Natural Procreative Technology, by Subsequent

Conception Status

Patient Characteristic

All

Eligible Couples*

NPT Treatment,

Conceived

NPT Treatment,

Did Not Conceive

Total (n) †

1072

364

708

Woman’s age (mean years

range

)

35.8 (25–48)

34.8 (25–45)

36.4 (26–48)

Prior years attempting to conceive (mean

5.6 (1–20)

4.8 (1–17)

6.1 (1–20)

range

)

Had previous live birth (percent yes)

Received previous ART ‡

(percent yes)

*One hundred sixty-seven couples were not eligible because they had been trying for less than 1 year or because they did not complete

the evaluation after the initial consultation.

† Number of couples in each category. Age was available for all women. For previous years attempting to conceive, 30 (2.8%) had

missing data; for previous births, 30 (2.8%) had missing data; for previous ART, 20 (1.9%) had missing data.

‡ Assisted reproductive technology (ART) includes in vitro fertilization with or without intracytoplasmic sperm injection.

The most common treatments given to women

included clomiphene (75.3%), support of luteal

hormonal production with human chorionic go-

nadotropin (67%) or progesterone (18%), and

medications to enhance cervical mucus production

(71%). Fifty-four women (5%) conceived without

medical intervention, using only Creighton Model

fertility charting and optimally timed intercourse.

There were 354 clinically recognized concep-

tions within 24 months after starting NPT treat-

ment, with cumulative crude proportions of live

births of 19.1 per 100 couples up to 12 months, and

25.5 up to 24 months, as shown in Table 3. Adjust-

ing for withdrawals from treatment and continuing

treatment at the end of study follow-up, the cumu-

lative proportion of ﬁrst live births was 27.1 up to

12 months, and 52.8 at 24 months. The propor-

tions with any conception (regardless of its out-

come) were higher: 25.9 crude and 35.5 adjusted at

12 months, and 33.0 crude and 64.8 adjusted at 24

months. Of conceptions within 2 years leading to a

live birth, 75% (205 of 273) occurred within 12

months and 93% (255 of 273) occurred within 18

months.

Several couple characteristics were associated

with the probability of live birth, as shown in Table

4. The cumulative proportion of live births de-

clined with increasing age of the woman. For

women under 30, the crude proportion of live birth

after 24 months was 33.7. For women over 40 the

crude proportion was 13.9. The cumulative crude

proportion of live birth also declined with increas-

ing previous attempts to conceive (36.6 for previous

time of 1 to 3 years; 11.9 for previous time more

than 9 years), and with the number of previous

ART attempts (30.8 for none, and 10.3 for 3 or

Table 2. Common Diagnoses of Couples Receiving Treatment Before and After Evaluation with Natural Procreative

Technology*

Diagnostic Category

Before NPT Evaluation

)

After NPT Evaluation

)

Unexplained infertility

506 (47.2)

5 (0.5)

Unexplained recurrent miscarriage

124 (11.6)

2 (0.2)

Anovulation

31 (2.9)

36 (3.4)

Polycystic ovarian syndrome

68 (6.3)

110 (10.3)

Endometriosis

209 (19.5)

208 (24.6)

Male factor

115 (10.7)

146 (13.6)

Limited cervical mucus

12 (1.1)

276 (25.7)

Suboptimal luteal progesterone

99 (9.2)

923 (86.1)

Suboptimal luteal estrogen

2 (0.2)

676 (63.1)

*This table is based on the 1072 couples that initiated evaluation. Diagnostic categories sum to more than 100% because couples could

have more than one diagnosis (other than unexplained).

378

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September–October 2008 Vol. 21 No. 5

http://www.jabfm.org

Table 3. Cumulative Outcomes per 100 Couples by Time Completed in Natural Procreative Technology Evaluation

and Treatment

Cumulative

Withdrawals

from

NPT (n

“proportion”)

Conceptions

Live Births*

Time Interval

(months)

Starting

at Time

Interval

(n)

Cumulative

Conceptions

(n)

Crude

Proportion

Adjusted

Proportion †

Starting at

Time

Interval

(n)

Cumulative

Live Births

(n)

Crude

Proportion

Adjusted

Proportion †

0–3

105 (9.8)

1072

7.0

7.3

1072

5.1

5.4

4–6

233 (21.7)

892

152

14.2

15.9

895

111

10.4

11.8

7–12

478 (44.6)

687

278

25.9

35.5

694

205

19.1

27.1

13–18

624 (58.2)

316

326

30.4

48.5

337

255

23.8

41.8

19–24

672 (62.7)

122

354

33.0

64.8

132

273

25.5

52.8

25–36 ‡

364

286

*Live births are assigned the time interval when the conception occurred rather than when the birth occurred.

† Adjusted by life-table analysis, where withdrawal or continuing treatment at the end of study follow-up are censoring events.

‡ Proportions are not calculated beyond 24 months.

more). Women with a previous birth had a higher

cumulative crude proportion of live birth (35.8)

than those without (23.1). The adjusted propor-

tions conﬁrm the same trends but should not be

considered reliable as precise estimates because

most of the subgroup life table analyses involve

small numbers of women continuing treatment un-

til 24 months (ie, fewer than 25 women).

Among all live births observed, there were 13

twin births (4.6%) and no higher order births. At

least 88% of all births were to term and did not

have low birth weight (Table 5). None of the pa-

Table 4. Live Births per 100 Couples at 24 months of Natural Procreative Technology Treatment by Characteristics

of Couples Beginning Treatment

Couple Category

Couples (n) Live Births (n) Crude Proportion Adjusted Proportion*

All couples

1072

273

25.5

52.8

Woman’s age (years)

33.7

59.1

30–35

412

134

32.5

58.6

35–40

423

21.0

46.1

151

13.9

50.9

Time spent attempting to conceive (years)

1–3

246

36.6

66.0

3–6

468

129

27.6

55.4

6–9

210

18.6

44.9

118

11.9

42.8

Previous live birth

Yes

257

35.8

73.9

785

181

23.1

48.5

Previous ART attempts (n) †

702

216

30.8

61.5

128

22.7

41.9

125

14.4

34.9

10.3

19.8

*Adjusted by life-table analysis, where withdrawal or continuing treatment at the end of study follow-up are censoring events. Adjusted

proportions should be interpreted with caution because of small numbers in subgroups.

† Assisted Reproductive Technology (ART) includes in vitro fertilization (IVF) with or without intracytoplasmic sperm injection

(ICSI).

doi: 10.3122/jabfm.2008.05.070239

Treatment of Infertility with Natural Procreative Technology 379

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