Kurztitel? Cycle Monitors and Devices in Natural Family Planning

G. Freundl1, P. Frank-Herrmann2, Ch. Gnoth3

For awareness based methods (FAB)-users charting and checking of symptoms may be supported by different instruments and devices. These cycle monitors promise to detect the fertile and infertile days by using direct and indirect markers of fertility in a woman´s menstrual cycle. In this article we use data of our own studies, data out of the literature research in Medline and PubMed and from our own German NFP (natural family planning)-database. We tried to rate the efficacy of the tested monitors. We figured out that only for one hormone- and for one temperature-computer reasonable prospective studies exist. To get more comparable results we have performed in 2000 a small pilot study on 6 devices and the symptothermal method of NFP (NFP-DAG) together with “Stiftung Warentest”. The efficacy of the various devices differed significantly. We therefore urgently need more clinical studies on menstrual cycle monitors for reliable information of the users. J Reproduktionsmed Endokrinol 2010; 7 (Sonderheft 1): 000–0. Key words: contraception, fertility, menstrual cycle, cycle monitor, cycle devices, natural family planning, NFP, fertility awareness based methods, symptothermal method, STM

„ Introduction ness of 0.4 per 100 women attempting to avoid by ab- years, provided the appropriate guide- staining from unprotected intercourse on Every menstrual cycle has a fertile win- lines are consistently adhered to [5]. those days they identify as fertile, are dow of several days in which a woman Therefore this method is one of the most bothered by the fact that their observa- may become pregnant from unprotected effective methods of family planning tions require them to abstain from unpro- intercourse with varying degrees of like- and may also be an option for patients at tected intercourse for more days than lihood [1–3]. This fertile window lasts risk. may really necessary. from approximately five days prior to ovulation until the day after ovulation, Cervical Mucus Methods are single indi- Different Devices and Evalua- with the probability of pregnancy in- cator methods (e. g. the Billings-Ovula- tion Methods creasing from approximately 10 % from tion Method or new simplified mucus Table 1 summarizes the indicators used unprotected intercourse five days before methods like the TDM) which are suit- in different devices developed for cycle ovulation to about 33 % on the day of able for developing countries due to only monitoring. There are indirect markers ovulation, decreasing rapidly to virtually a medium efficacy; same with the Stan- like basal body temperature (BBT), elec- zero within 24 hours after ovulation has dard Days Method which is a simple cal- trical resistance of the cervical mucus, occurred. The length of the fertile win- endar rule for developing countries [6]. crystallisation phenomenon of cervical dow is physiologically based on the in mucus, electrostatic charge, enzymes, vivo lifetime of the gametes and deter- NFP may be integrated also into the ions, sugars and proteins of the cervical mined by the conception probabilities management of subfertility and it makes mucus and the vaginal fluid and there are from intercourse on the different cycle an interesting contribution to gynaeco- direct markers of ovulation like ovarian days. logical endocrinology: long-term cycle sonomorphology and ovarian hormons. monitoring may support medical diag- Also the trade names of the currently Today, women are able to reliably ob- nosis and therapy. For all applications, it available products are shown. serve the fertile window as well as peak has turned out that effective use depends fertility in the cycle without much effort. on good instruction of the women [4]. There are devices which were devel- They develop a high level of reproduc- Medical doctors may be supported by oped, tested and have been shown to be tive competence which can be used in qualified local NFP teachers. of limited usefulness or to be really ben- various situations. Menstrual cycle de- eficial. Relatively few of them have been pending changes in the levels of oestro- Why Cycle Monitors and Gad- subjected to rigorous testing, and several gen and progesterone, produce observ- gets? have being actively marketed without able signs of fertility. The German NFP For developers of technical tools it is in- sufficient evidence of their ability to ac- method combines the observation of the teresting, that for some women monitor- curately identify the fertile days of the periovulatory temperature rise and cer- ing their fertility signs in the conven- menstrual cycle. Indeed, there are no vical mucus changes and determines the tional way may be difficult and inconve- clear guidelines for testing these de- onset as well as the end of the fertile nient. Additionally, some women lack vices. phase according to the double-check confidence in their subjective observa- principle (Symptothermal Method) [4]. tions and interpretations of their fertility According to a suggestion made by Actual data found a method-effective- signs. Others, particularly those who are Martinez et al., 1995 [7] we shortly want

Received: XX. XX. 2010; accepted: July 16, 2010 From the 1Section Natural Fertility of the German Society of Gynaecological Endocrinology and Fertility Medicine, Düsseldorf; the 2Department of Gynaecology and Fertility Disorders, University of Heidelberg and the 3Praxisklinik für Reproduktionsmedizin Grevenbroich und Universitätsfrauenklinik Köl Correspondence: Prof. Dr. G. Freundl, NFP-Projekte an der H.H.-Universität Düsseldorf, Städtisches Krankenhaus Düsseldorf-Benrath, D-40593 Düsseldorf, Urdenbacher Allee 83; e-mail [email protected]

J Reproduktionsmed Endokrinol 2010; 7 (Sonderheft 1) 1 Kurztitel?

each cycle of use) and the results of Table 1: Indicators used in devices developed for cycle monitoring typical use of the device (i. e., the likeli- Indicator used Devices hood of pregnancy experienced by women who do not always use the infor- BBT Babycomp/ Ladycomp, Bioself, Cyclotest mation provided by the device correctly Cervical mucus: electrical resistance CUE-Fertility Monitor; Dist4 Cervical mucus: crystallisation PC 2000; PG 53; Maybe Baby and consistently during each cycle of PCO2 Capnodig use). Electrostatic charge Ovulation controller Pregnandiol-G and E1-3G, Brown‘s Ovarian Monitor „ Evaluation of Published LH/E3G Persona Data Basal body temperature/LH or cervical mucus Cyclotest 2 plus Progesteron Safeplan SystemsUsing Indirect Markers Lipid-profile Skin-check There are five devices reported in the lit- erature which measure indirect markers of the fertility status. The data are of to review what has been done so far and would have been provided by the de- variable quality, and only one, the comment on published results in the or- vice can be compared to the NFP Bioself has recently undergone a pro- der of indirect markers and direct mark- charts. If we find, for example, that spective efficacy study. ers of fertility. the STM identified days 8–16 of a particular cycle as fertile, and the de- Temperature Computers Generally, so called New technologies vice would have identified only days 1. Ladycomb®/Babycomp (NT) for identifying the fertile days of 10–16 as fertile, this would suggest Effectiveness finding studies (EFS) the menstrual cycle should be assessed that the device is not sufficiently ac- a) Indirect EFS: Freundl et al. [8] in two ways: Efficacy-Finding Studies curate in determining the beginning have compared in 168 cycles the (EFS), and Effectiveness Studies (ES). of the fertile time. fertile time detected using the 2. Alternatively, in a “direct” EFS, the STM of NFP with the FT detected An EFS precedes an ES and it is essential information provided by the device by the device. Only in one cycle to conduct both types of studies in order can be compared to direct observa- the device failed completely. In 3 to evaluate the appropriateness of a tech- tions of the woman’s fertility status: cycles the beginning of the fertile nology or device for use by women who Ultrasound for evaluating follicular time was located at day –4, in 1 wish to avoid a pregnancy in a first line. development combined with serum cycle at day –2. The end of fertile An EFS compares the fertile phase of the hormone assays (estradiol, LH, and time was shown at day 0 in 1 case menstrual cycle detected by the device to progesterone). If the device identi- and at day +1 in 2 cycles. The du- the fertile phase detected by another es- fies a fertile window that is consis- ration of fertility according to this tablished and reliable reference method. tent with the results of these tests, we device was 16.88 ± 5,63days. This is sufficient to assume that the de- can rely that it is likely to provide b) Direct EFS: To have a more accu- vice helps to identify the fertile phase appropriate information to a users rate comparison the same authors (method performance), but it is not suffi- who want to avoid a pregnancy. For looked into the fertile time de- cient to confirm that the device is proven example, if the device identifies the tected by LH and ultrasound useful to prevent pregnancy (user perfor- onset of the fertile phase approxi- monitoring of the growing fol- mance). mately five days prior to ovulation, licle in 20 cycles. In no case the as determined by vaginal ultrasound recognition of the defined fertile An EFS is clearly the first step in assess- and hormone assays, and identifies phase was missed by the device ing the potential appropriateness of a de- when ovulation has occurred, it is [8]. In 1992 the same group has vice for a woman who wants to avoid highly likely to give useful and suffi- performed such an study with pregnancy. There are two ways to ap- cient information. Ladycomp only [9]. proach an EFS. An ES determines the effectiveness of Efficacy studies (ES) 1. In an “indirect” EFS, the information the device in preventing a pregnancy With BC/LC there is one retrospec- produced by the device may be com- (user performance), which is the prop- tive efficacy study (rES) available. pared to the information produced by erty of the device to provide accurate and The data were collected in the fol- the use of an established reference timely information that allows users to lowing way: after tracing the ad- method of Natural Family Planning avoid pregnancy by abstaining from dresses of purchasers of BC/LC over (NFP), such as the Sympto-Thermal intercourse or using a barrier method the past 3 years, questionnaires were Method (STM). In this instance, of contraception during the identified sent to 800 German purchasers. 182 charts from women who have re- fertile time. An ES also provides final letters came back unopened as the corded their observations of their fer- information about the results of perfect addressees had changed their homes tility signs and identified the fertile and imperfect use of the device (i.e., the and the new addresses were not phase of their menstrual cycles can likelihood of pregnancy if the woman known. 16 customers had bought de- be used as the basis of comparison. uses the information provided by the vices but had not used them. Conse- The information that theoretically device correctly and consistently during quently, 602 were able to answer the

2 J Reproduktionsmed Endokrinol 2010; 7 (Sonderheft 1) Kurztitel?

questionnaire. Of these, 538 returned 3. Bioself would not appear. The women were the questionnaires, resulting in an With Bioself 110® a number of stud- asked to use the device for 3 cycles. answering rate of 89.7 %. In the ies have been performed [13–16]. The information of the device‘s same way, 110 questionnaires were Unfortunately this device has been memory was printed out monthly. collected from Switzerland. Thus, removed from the market about 2 These 60 women contributed 252 for the statistical analysis a total of years ago. cycles. Of these in 24 cycles there 538 + 110 = 648 questionnaires were Ismail et al. [15] have performed was no LH-peak, in 20 cycles were included in the study [10]. a EFS with 33 women contributing < 23 or > 35 days, in 3 cycles there was The most important question re- altogether 88 cycles. 24 women used malfunction of the Bioself, 5 women ferred to the occurrence of pregnancy the device to help them to achieve a did not take temperature properly. while using the device. When we pregnancy, while 9 were using it as a For the final analysis 200 cycles heard about a pregnancy we exam- contraceptive aid. 8 of the first group remained to answer the question on ined the type of pregnancy according conceived during the study. Interest- the correlation between the reference to the opinion of the user: Did it oc- ingly in 7 of the 9 couples preventing fertile time and first and last fertile cur during the use of the device? Did a pregnancy the partners used also day detected by the device. the BC/LC show a green, red or yel- condoms and 5 of the volunteers also It was found that in 4 cycles (2 %) low light? When had the intercourse used natural methods! However, one out of 200 the red light started one taken place? of the nine women had an unplanned day in the fertile time, in 5 (2.5 %) With the rES in 597 women with pregnancy during the study. But her cycles 2 days in the FT and in 1 10275 cycles 33 pregnancies oc- contraceptive intention was not clear. (0.5 %) on the third day prior to the curred, which gives a Pearl-Index of The effectiveness of the Bioself expected ovulation: 10 cycles in risk 3.8. With the data reported it is not 110 was evaluated by comparing the prior to ovulation! possible to determine failure rates information it provides with four The green light after ovulation with perfect and typical use. The “objective” indicators such as ultra- started in 2 cases at –1, in 2 cases at cycle length (mean, SD) was 29.2 ± sound, luteinizing hormone (LH), +1 and in 7 cases at +2. 5.4 days, the length of the fertile basal body temperature and cervical Altogether the risk of pregnancy phase was 16.3 ± 4.6 days. mucus characteristics. was given in 11 (6.2 %) out of 178 From 88 cycles available for cycles. 2. Cyclotest analysis 11 (12.5 %) were excluded Summarized the green signal ap- With the Cyclotest-system until now for different reasons. From the re- peared in 11 (6.2 %) out of 178 cycles only EFS are published. The design maining 88 cycles there were 75 with during the postovulatory fertile time, of the studies is the same as reported LH data, 68 with ultrasound and 66 the red light appeared to late in the for the BC/L: the number of cycles in with both. Finally for analysis of the preovulatory fertile time in 10 the indirect EFS was 16, the number fertile period data were available for (5.6 %) out of 178 cycles. So the total in the direct test was 5 [11]. 65 cycles using US and Bioself and failure rate was 11.8 %. With the Cyclotest 2 plus device 72 cycles using LH and Bioself. For Drouin et al. [17] reports on a an indirect EFS was performed using analysis of the postovulatory infertile prospective three-center-study evalu- cycles estimated according to STM- period, data were available for 63 ating the Bioself as an contraceptive rules as comparison [12]. Always the cycles using US and Bioself and 71 aid. 83 women accumulated 745 13. cycle of 207 women which con- cycles using LH and Bioself. Out of cycles. The study design fitted into tributed 4430 cycles alltogether 77 cycles in 4 cycles the green signal our rES-concept. 6 unplanned preg- were used for evaluation. It was appeared during the postovulatory nancies occurred from unprotected found that the algorithm led to dan- fertile time, in 7 cycles in the possi- intercourse during the fertile phase of gerous reduction of the fertile time bly fertile time. the cycle, as indicated by the Bioself (FT) in only 2 out of 207 women Labrecque et al. [16] also per- device. The pregnancy rate was 9.02 cycles (0.96 %). At the end of fertile formed an EFS comparing the results per 100 women-years. time the device requested more absti- of the Bioself 110 with a reference In our study in 3 of 42 cycles the nence than was necessary in about method, the Ovustick LH-surge de- beginning of the postovulatory infer- 12 % of the cycles. tection kit, which detects the LH- tile phase felt into the time of ovula- With the Cyclotest 2 plus system peak on average 24–30 hours before tion [14]. there is a possibility to enter the ovulation. Flynn has reported on a well done symptom of mucus of highest quality For the purpose of this study the Bioself 110 study which was per- or the peak day of LH measured by fertile period was assumed to be 6 formed as a pES [13]. 150 sexually an urine strip. So this computer uses days, starting 3 days before the LH- active women (age 18–40) were re- a double check observation to calcu- peak and ending on the second day cruited for participation in a 24- late the fertile time. It seems that with after the LH-peak. months study. After discontinuation the addition of another parameter it is 60 women (age 21–40 years) were for various reasons a total of 131 possible to shorten the length of the recruited into the study with regular women entered the study and con- abstinence (from 15.8 per cycle menstrual cycles (23–33 days). Inter- tributed 1238 cycles. 80 women stayed down to 15.14 ± 5.63 days of absti- estingly in this study the Bioself 110 in the study until its termination. 41 nence per cycle). was modified so that the light signal women completed 12 cycles or more.

J Reproduktionsmed Endokrinol 2010; 7 (Sonderheft 1) 3 Kurztitel?

methodology used corresponds to the Table 2: Reports on the Cue Fertility Monitor EFS it is expected that further testing for Cycles Mean fertile time Failurerate (n/%) Study Design Ref. efficacy is not necessary.

29 9,6 EFS [22,51] Endexspiratory CO -Pressure Change 30 4/13,8 % EFS [23] 2 18 8,5 7/38,9 % EFS [52] during Cycle Döring [25, 26] observed that the pCO 65 9,8 35/53,8 % EFS [21] 2 values were significantly higher during the follicular phase than during the luteal A total of 30 pregnancies resulted Electrical Resistance Gauges phase of the cycle. In the way of an EFS from all cases. 2 pregnancies resulted Cue Fertility Monitor the time course of the endexspiratory

from an apparent failure of the Attempts were made to measure the elec- pressure of CO2 was determined daily Bioself 110. According to analysis of trical resistance of saliva or vaginal fluid during the menstrual cycle of 15 women

the manufacturer nine (5.1 %) of the [20], which have been found to fluctuate using the Capnodig CO2, Monitor of 175 devices in the study were actu- during the cycle. Table 2 shows some Dräger AG, Lübeck, Germany. This was ally defective. In a maximum of 116 studies and the results performed with correlated to the changes of LH, E2 and cycles the algorithm of Bioself 110 the Cue Fertility Monitor®. Progesterone in serum and the basal was unable to identify a temperature body temperature [27]. There is a sig-

shift. Our studies have shown [21] that there nificant reduction of the pCO2 in the ex- It has to be mentioned that this are many cycles where the CUE signals piratory flow already 1–2 days prior to prospective study gives also the fig- can be found. However, in about one- LH-peak. With 6 volunteers this reduc- ures for perfect and imperfect use of third of the cycles the signal (Cue peak) tion happened at day –1, with 4 women the device. could not be found. The beginning of the with day –2, with 3 women with day –3 Summarized the method failure fertile time was captured easily in almost and with 1 woman with day –4. The pre- rate (according to Pearl) was 1.9 in all cycles (control-cycles: 14 out of 14 liminary results show that the method this study. [100 %], NFP-cycles 41 out of 49 may be useful for ovulation detection, [83.7 %]). However, the end of fertile but will not be expected to give suffi- Self Tests for Body Fluids time was detected to early in 13 out of 14 cient warning for abstaining intercourse PC 2000, PG 53 and 41 out of 49 (83.7 %). to prevent pregnancy. Recently there are With other devices the ferning phenom- more studies available showing that the enon is used occurring when cervical Moreno reports on 29 cycles from 11 CO2 pressure is more convenient to pre- mucus or saliva are drying on a fat-free women [22]. In contrast to our findings dict ovulation in dealing with fertility slide in open air. Unfortunately only all but one of the 29 cycles were associ- problems [28–30]. very few studies in EFS-design are per- ated with an oral peak and a vaginal na- formed until now: Jordan et al., 1992 dir. A nadir in vaginal readings occurred Other Developments found with 300 cycles of use a total fail- on or before the expected ovulation day There are technical developments which ure rate of 18.4 % [18]. (EOD) in all but one of the cycles are not generally recognised as they are (3.5 %). 93 % of the salivary electrical using rather unknown indicators of the Barbato et al., 1993, using the PG53 re- resistance (SER) nadirs occurred within woman’s cycle fertility: ported in a similar setting with 32 cycles two days prior to EOD. a failure rate of 12.5 % [19]: of the 32 Stoller et al., 1986 report on a device, women participating in this research, 28 Loewit reported a failure rate of 4 out of which measures changes of the electrical women had a good salivary test with 30 (13.8 %) [23]. potency of the fingertip [31]. Treves et positive ferning by the microscope in the al. has reported on changes in enzyme same period as other markers of fertility. As there are characteristic cyclic changes levels in human cervical mucus during In 4 cycles the ferning was uninterpret- of salivary electrical resistance, it may the menstrual cycle [32]. Calamera re- able as there was no correspondence be possible that the device can increase ports on changes in sialic acid concentra- with the cycle phase. Ferning began 1–2 its safety for the users by improving the tion in human saliva during the men- days before cervical mucus appearance, algorithm for evaluation. strual cycle [33]. Mancuso, 1992 reports and lasted a mean of 6.2 days. Ferning on a device showing the proportion of occurred, on average, 7.2 days before the Roumen and Dieben [24] reports of 27 palmitin acid and cholesterol in the skin first day of temperature shift. The au- cycles in 18 volunteers and the relation- of the face [34, 35]. Others report on a thors concluded that there is a direct cor- ship between the SER and the time of brassiere measuring the of temperature relation between salivary ferning and ovulation. They found that the changes and the circulation of the breast tissue fertile period. Salivary ferning may be in SER values, arranged to the LH-peak caused by estrogens. used as a new parameter to aid women to were not statistically significant. The detect the fertile period in combination days of SER peak in relation to the day Last but not least a wrist-watch has been with other symptothermal methods of of LH peak were not reproducible in in- developed by Weiland, which measures ovulation detection. Further research in dividual women. They concluded that the surface temperature at the wrist . In order to improve the use-effectiveness of measuring the SER is of no use in pre- 1983 this watch was honored by the salivary ferning is needed. dicting the day of ovulation. As the Phillip-Morris-research price. All these

4 J Reproduktionsmed Endokrinol 2010; 7 (Sonderheft 1) Kurztitel?

Table 3: Devices compared in a small pilotstudy in respect of their contraceptive efficacy. Only the Brown’s Ovarian Monitor was not tested in this context. The devices were compared with our STM (NFP-DAG) [4, 53]

Product Price (approx., €) Method www Manufacturer

Babycomp/Ladycomp 750 Temperature computer, www.babycomp-ladycomp.com Valley electronics GmbH BBT and calculation rules Wengwiese 3, D-82438 Eschenlohe, Germany Cyclotest 2 Plus 150 Temperature computer, www.cyclotest.de UEBE GmbH BBT and calculation rules Zum Ottersberg 9, D-97877 Wertheim, Germany Brown‘s Ovarian Monitor 100 + 0.5/assay tube Hormone computer: ? St. Michael NFP Services Pregnandiol-G and E1-3G Persona 150 + 12 €/month Hormone computer: www.persona.org.uk Unipath GmbH for teststicks LH & E3G, calculation rules An Lyskirchen 14, D-50676 Köln, Germany PC 2000 60 Mini-microscope, www.thedonna.com IMPCON ferning pattern of saliva PG 53 39 Mini-microscope, www.intercom.es/pg53 Aplicationes Opticas PG/53 ferning pattern of saliva or Paseo de Gracia 53, cervical mucus ES-08008 Barcelona, Spain Maybe Baby 80 Mini- microscope, www.maybe-baby.com OPTIX ferning pattern of saliva Wiesenstraße 58, D-63071 Offenbach, Germany developments are interesting, but none ing the late safe days defined by the of the system resulted in 33 method of them have been tested in carefully de- Monitor, but some early-day preg- related pregnancies giving a method signed studies. nancies occurred through long sperm pregnancy rate of 12 % during per- survivals of 6 to 8 days, mostly dur- fect use. This should be ameliorated Systems Using Direct Markers ing the return of fertility after breast- to an estimated pregnancy rate of Hormonal Computers feeding [37–44]. 6 % after some changes of the 1. Brown’s Ovulation Monitor algorhithm. The Monitor assists the woman to 2. Persona avoid a pregnancy by periodic absti- Another approach to identify the fer- „ Comparative Trial nence [36] or to achieve a pregnancy tile phase of the menstrual cycle is by timing intercourse to the most fer- the device Persona that allows a As no comparable results concerning the tile days of the cycle. Ovarian and woman to measure cyclical changes different devices were available so far pituitary hormone production show of estrogens and LH in urine. A we have performed a small clinical ob- characteristic patterns during the hand-held monitor and disposable servational pilot study [47] with the fol- cycle. Urinary estrone and preg- test sticks measures changes in the lowing design: nanediol glucuronide measurements urinary levels of E3G and LH and a • Objectives: The effectiveness of cycle yield reliable information concern- program calculated the stage of the monitors like temperature computers ing the beginning, peak, and end of cycle. Estrone-glucuronide should (Babycomp/Ladcomp, Cyclotest 2 Plus, the fertile period. Enzyme immu- be able to mark the beginning of Bioself 2000), a hormonal computer noassays for urinary estrone and the fertile phase, while LH is used to (Persona), mini-microscopes (PC 2000, pregnanediol glucuronides were de- detect the end of the fertile phase. PG 53, MayBe Baby) and the Sympto- veloped so that they can be per- Until now, it has been difficult to thermal Method (STM) of Natural formed at home. The tests gave 4 identify a precise measurable hor- Family Planning (NFP) in detecting days or more warning of ovulation in monal marker for the beginning of the fertile window in a woman’s cycle 99 % of cycles and allowed inter- the fertile phase. was evaluated. Table 3 shows the de- course to be resumed 1 to 3 days after The results of a prospective effi- tails of the devices and computers ovulation in 88 %, giving a mean cacy study (pES) on Persona® have tested. period of abstinence of 7 days. No been reported in 1999 (see also [1, • Materials and Methods: A total of 65 woman had difficulties with the daily 45, 46]): 710 women have contrib- women have tested two of the above urine testing, and their results consis- uted 6833 cycles. The trial was de- devices in variable combinations after tently identified the distinctive hor- signed to determine the method ef- a learning phase. 122 test cycles and mone pattern of the ovulatory cycle fectiveness of personal hormone 558 learning cycles were available for for each individual including the day monitoring in preventing pregnancy evaluation. In the test cycle the fertile of ovulation and correlated closely when used with abstinence from window was detected using the usual with the mucus symptoms. No preg- during the identi- tools (LH-Peak testing and sonogra- nancy occurred from intercourse dur- fied fertile days of the cycle. The use phy of the growing follicle).

J Reproduktionsmed Endokrinol 2010; 7 (Sonderheft 1) 5 Kurztitel?

They are sold without having any sound Table 4: Detection of cycle days as fertile or infertile in relation to the clinical status as revealed by ultrasound and daily urinary LH (false negative: defines a day scientifical basis. Therefore, we as the predicted as infertile by the monitor was clinically fertile , false positive: a day advocates of the users can not recom- predicted as fertile by the monitor was clinically infertile) [44] mend them.

Absolute numbers and rates (%t) Women Cycle days „ Relevanz für die Praxis 1) 2) 3) Device/Method n1 n2 false neg. false pos. correct PG 53 16 460 94 73.4 22 6.6 344 74.8 Es werden immer mehr Geräte ange- PC 2000 14 387 65 58.0 31 11.3 291 75.2 boten, die einer Frau die Beurteilung Maybe Baby 16 441 66 51.6 71 22.7 304 68.9 ihre persönlichen aktuellen Frucht- Persona 15 416 25 20.8 68 23.0 323 77.6 barkeit erleichtern sollen. In der Bera- Babycomp/LC 16 442 6 4.7 92 29.3 344 77.8 tung muss man die Frau darauf auf- Bioself 2000 15 454 9 7.5 180 53.9 265 58.4 merksam machen, dass nur wenige Cyclotest 2 Plus 15 392 2 1.7 108 39.7 282 71.9 Geräte heute hinsichtlich ihrer Zuver- NFP 15 416 0 0.0 75 25.3 341 82.0 lässigkeit ausreichend getestet sind.

1) related to total number of fertile cycle days (n1 × 8) 2) related to total number of infertile days (n2 – n1 × 8) 3) References: related to all cycle days (n2) 1. Bremme J. Sexualverhalten und Konzeptionswahrscheinlich- keit (Auswertung einer prospektiven Studie zur Natürlichen Familienplanung); Med. Fakultät der Heinrich-Heine-Universi- • Results: The number of women and computers were estimated to be tät Düsseldorf, 1991; 1–52. 2. Freundl G. Rhythm methods and devices; in Capdevilla C, cycles in whom/in which the various 0.0134–0.0336, for the hormonal com- Cortit L, Creatsas G (eds). Contraception today.The Internatio- devices indicated false negative (not puter 0.1155 and for mini-micro- nal Congress, Symposium and Seminar Series. The Parthenon fertile in the true fertile phase) or false scopes 0.2313–0.2369. For the STM Publishing Group, New York, London,1999; 53–64. 3. Wilcox AJ, Dunson D, Baird DD. The timing of the “fertile positive (fertile in the true non-fertile of NFP, there were no false infertile window” in the menstrual cycle: day specific estimates from a phase) differed significantly. The tem- days. Thus the estimated pregnancy prospective study. BMJ 2000; 321: 1259–62. 4. Arbeitsgruppe NFP. Natürlich und sicher. 17. Aufl. Trias Ver- perature computers indicated false rate per cycle turned out to be 0. lag, München, 2005. negative days in 1.7 % to 7.5 %, the • Summary: The symptothermal method 5. Frank-Herrmann P, Heil J, Gnoth C, Toledo E, Baur S, Pyper hormonal computer in 20.8 %, the of NFP is the most effective contra- C, Jenetzky E, Strowitzki T, Freundl G. The effectiveness of a fertility awareness based method to avoid pregnancy in rela- mini-microscopes between 51.8 % ceptive method as it has the lowest tion to a couple’s sexual behaviour during the fertile time: a and 73.4 % and NFP in 0 %. Compar- false negative (not fertile in the true prospective longitudinal study. Hum Reprod 2007; 22: 1310–9. 6. Raith-Paula E, Frank-Herrmann P, Freundl G, Strowitzki T. ing the length of the preovulatory in- fertile phase) rate among all the meth- Natürliche Familienplanung heute. 4. Aufl. Springer Verlag, fertile time the PC 2000, Bioself 2000 ods tested. But the period of absti- Heidelberg, 2008. and NFP differed significantly from nence required is somewhat longer 7. Martinez AR, Zinaman MJ, Jennings VH, Lamprecht VM. Prediction and detection of the fertile period: the markers. Int Cyclotest 2 Plus and MayBe Baby; in compared to other monitors. The esti- J Fertil Menopausal Stud 1995; 40: 139–55. the postovulatory infertile time only mated efficacy of the Fertility moni- 8. Arbeitsgruppe NFP. Natürliche Familienplanung: neue Tech- nologien und Studien zur Methode. In: Arbeitsgruppe NFP NFP and PC 2000 differed signifi- tors range from the temperature com- (Hrsg). Düsseldorf, Bundesfamilienministerium Bonn, 1991. cantly from Cyclotest 2 Plus and puters (upper level) to the hormonal 9. Freundl G, Baur S, Bremme M, Döring G, Frank-Herrmann P. MayBe Baby; in the length of the fer- computer (medium level) and the Ladycomp as an aid in natural family planning. Advances In Contraception 1992; 8: 184. tile time only Bioself and PC 2000 dif- mini-microscopes with very low esti- 10. Freundl G, Frank-Herrmann P, Godehardt E, Klemm R, fered significantly. mated contraceptive efficacy. The Bachhofer M. Retrospective clinical trial of contraceptive effectiveness of the electronic fertility indicator Ladycomp/ • Conclusions: For contraception pur- false negative results deserve our spe- Babycomp. Adv Contracept 1998; 14: 97–108. poses the devices and methods tested cial interest, as they are connected 11. Bremme M, Freundl G, Frank-Herrmann P. Analysis of the vary: the best results were obtained with the efficacy of the systems used computerthermometer “Cyclotest D” to be used for natural family planning. Advances In Contraception 1992; 8: 221. with the symptothermal method of (Tab. 4). 12. Freundl G, Frank-Herrmann P, Bremme M. Results of an Natural Family Planning followed by efficacy-finding study (EFS) with the computer-thermometer the temperature computers and Persona. Cyclotest 2 plus containng 207 cycles. Adv Contracept 1998; „ Conclusions 14: 201–7. The mini-microscopes are not recom- 13. Flynn A, Pulcrano J, Royston P, Spieler J. An evaluation of mendable. For achieving a pregnancy Until now there has been no device the Bioself 110 electronic fertility indicator as a contraceptive aid. Contraception 1991; 44: 125–39. the devices show more positive results. tested which has a method effectiveness 14. Freundl G, Baur S, Bremme M, Döring G, Frank-Herrmann • General outlook: To generate a simple comparable to the German sympto- P, Godehardt E, Kunert J. Temperaturcomputer zur Bestim- mung der fertilen Zeit im Zyklus der Frau: Babycomp, Bioself but effective way to predetermine the thermal method which is in the high effi- 110, Cyclotest D. Fertilität 1992; 8: 66–76. ® practical value of a new device we es- cacy range [49, 50]. Only Persona and 15. Ismail M, Arshat H, Pulcrano J, Royston P, Spieler J. An timated for every device the maximum Bioself® have been tested in prospective evaluation of the Bioself 110 fertility indicator. Contraception 1989; 39: 53–71. failure rates using the daily conception effectiveness studies (pES). We there- 16. Labrecque M, Drouin J, Rioux JE, Gingras S, Spieler JM. probability rates taken from the Euro- fore still need well designed prospective Validity of the Bioself 110 fertility indicator. Fertil Steril 1989; pean Fecundability Study. Intercourse effectiveness studies (pES) on all the 52: 604–8. 17. Drouin J, Guilbert EE, Desaulniers G. Contraceptive appli- was assumed to occur on each of devices which are sold over-the-counter. cation of the Bioself fertility indicator. Contraception 1994; falsely predicted days of infertility 50: 229–38. 18. Jordan V, Pilka L, Roztozil A. The possibility of natural [48]. The maximum unintended preg- Other devices have still been rejected to family planning by means of estrogen peak evaluation in sa- nancy rates per cycle for temperature be tested carefully in any kind of studies. liva. Advances In Contraception 1992; 8: 223–4.

6 J Reproduktionsmed Endokrinol 2010; 7 (Sonderheft 1) Kurztitel?

19. Barbato M, Pandolfi A, Guida M. A new diagnostic aid for 31. Stoller KP, Brooks PG. Detection of ovulation via fingertip 43. Blackwell LF, Brown JB, Vigil P, Gross B, Sufi S, d’Arcangues natural family planning. Adv Contracept 1993; 9: 335–40. electrical potentials: a preliminary report. Mt Sinai J Med C. Hormonal monitoring of ovarian activity using the Ovarian 20. Fazleabas AT, Segraves MM, Khan-Dawood FS. Evaluation 1986; 53: 506–9. Monitor: part I. Validation of home and laboratory results ob- of salivary and vaginal electrical resistance for determination 32. Treves C, Vincenzini MT, Vanni P, Bardazzi F, Cattaneo A, tained during ovulatory cycles by comparison with radioimmu- of the time of ovulation. Int J Fertil 1990; 35: 106–11. Ogier E. Changes in enzyme levels in human cervical mucus noassay. Steroids 2003; 68: 465–76. 21. Freundl G, Baur S, Bremme M, Döring G. Natürliche Fami- during the menstrual cycle. Int J Fertil 1986; 31: 59–66. 44. Brown JB. Ovarian activity and fertility and the Billings lienplanung: Neue Technologien und Studien zur Methode. 33. Calamera JC, Vilar O, Nicholson R. Changes in sialic acid ovulation method. Journal bitte ergänzen 2005; 1–8. BMJFG, BMJFG (Hrsg), 1991. concentration in human saliva during the menstrual cycle. Int 45. Freundl G, Bonnar J, Flynn A, Frank-Herrmann P, Kirkmann 22. Moreno JE, Khan DF, Goldzieher JW. Natural family plan- J Fertil 1986; 31: 43–5. R, Snowden R. [Contraception per computer. Hormone system ning: suitability of the CUE method for defining the time of 34. Mancuso S, Bellante F, Marana R, Angelini A. Chemical persona – results of studies in Germany]. Fortschr Med 1998; ovulation. Contraception 1997; 55: 233–7. changes in saliva during the menstural cycle. Acta Med Rom 116: 47–8. 23. Loewit K, Hoppichler F, Ledermuller G, Widhalm G. Ovula- 1978; 16: 387–403. 46. Bonnar J, Collins W, Freundl G, May K, Snowden R, Senior tion prediction from cyclic changes in salivary electrical con- 35. Mancuso S. New indicators and methods of the natural S. Natural Contraception through Personal Hormone Monitor- ductivity [letter]. Am J Obstet Gynecol 1990; 163: 708–10. regulation of fertility; Rom, Catholic University of the Sacred ing. Verlag/Ort bitte ergänzen. ed. 1, 1996. 24. Roumen FJ, Dieben TO. Ovulation prediction by monitoring Heart, 1992. 47. Freundl G, Frank-Herrmann P, Godehardt E, Kern PA, Klose A, salivary electrical resistance with the Cue Fertility Monitor. 36. Brown JB, Blackwell LF, Billings JJ, Conway B, Cox RI, Koubenec HJ, Gnoth Ch. Die Effektivität von Zyklusmonitoren Obstet Gynecol 1988; 71: 49–52. Garrett G, Holmes J, Smith MA. Natural family planning. Am zur Bestimmung des fertilen Fensters. Geburtsh Frauenheilkd 2003; 63: 778–84. 25. Döring G. Über rhythmische Schwankungen von Atmung J Obstet Gynecol 1987; 157: 1082–9. und Körpertemperatur im Menstruationszyklus. Pflügers Archiv 37. Brown JB, Blackwell LF. Ovarian Monitor Instruction 48. Freundl G, Godehardt E, Kern P, Frank-Herrmann P, Koubenec 1948; 250: 37–46. Manual. Melbourne, OM Research and Reference Center of H, Gnoth C. Estimated maximum failure rates of cycle monitors Australia, 1980. using daily conception probabilities in the menstrual cycle. 26. Döring G. Über Veränderungen der Atmung während des Hum Reprod 2003; 18: 2628–33. Zyklus. Arch Gynecol 1953; 182: 746–58. 38. Brown JB HPSMBH. Correlations between the mucus symptoms and the hormonal markers of fertility throughout re- 49. Freundl G, Sivin I, Batar I. State-of-the-art of non-hormonal 27. Jakob U, Britting R, Hetz W, Wildt L. Die Messung des methods of contraception: IV. Natural family planning. Eur J endexspiratorischen pCO zur Bestimmung des Ovulationszeit- productive life. Melbourne, The Ovulation Method Research 2 and Reference Centre of Australia, 1981. Contracept Reprod Health Care 2010; 15: 113–23. punktes (Measurement of Endexspiratory CO2 Pressure for Detecting Ovulation). Geburtsh Frauenheilkd 1997; 57: 549– 39. Brown JB, Blackwell LF, Holmes J, Smyth K. New assays 50. Freundl G, Freundl-Schütt T. Fertilitätscomputer und ihre 54. for identifying the fertile period. Suppl Int J Gynecol Obstet Wertigkeit. Gynäkologe 2006; 39: 678–89. 28. Hadziomerovic D, Moeller KT, Licht P, Hein A, Veitenhansel 1989; 1: 111–22. 51. Moreno JE, Weitzman GA, Doody MC, Gibbons WE, Besch S, Kusmitsch M, Wildt L. The biphasic pattern of end-expira- 40. Brown JB, Holmes J, Barker G. Use of the Home Ovarian P, Goldzieher JW. Temporal relation of ovulation to salivary tory carbon dioxide pressure: a method for identification of Monitor in pregnancy avoidance. Am J Obstet Gynecol 1991; and vaginal electrical resistance patterns: implications for the fertile phase of the menstrual cycle. Fertil Steril 2008; 90: 165: 2008–11. natural family planning. Contraception 1988; 38: 407–18. 731–6. 41. Blackwell LF, Brown JB. Application of time-series analy- 52. Freundl G, Bremme M, Frank-Herrmann P, Baur S, 29. Kaygisiz Z, Erkasap N, Soydan M. Cardiorespiratory re- sis for the recognition of increases in urinary estrogens as Godehardt E, Sottong U. The CUE Fertility Monitor compared sponses to submaximal incremental exercise are not affected markers for the beginning of the potentially fertile period. to ultrasound and LH peak measurements for fertile time ovu- by one night’s sleep deprivation during the follicular and luteal Steroids 1992; 57: 554–62. lation detection. Adv Contracept 1998; 12: 111–21. phases of the menstrual cycle. Indian J Physiol Pharmacol 42. Blackwell LF, Brown JB, Cooke D. Definition of the poten- 53. Arbeitsgruppe NFP. Natürlich und Sicher. Arbeitsheft. 2003; 47: 279–87. tially fertile period from urinary steroid excretion rates. Part II. 8. Aufl. Trias Verlag, Stuttgart, 2009. 30. Ott HW, Mattle V, Zimmermann US, Licht P, Moeller K, A threshold value for pregnanediol glucuronide as a marker Wildt L. Symptoms of premenstrual syndrome may be caused for the end of the potentially fertile period in the human men- by hyperventilation. Fertil Steril 2006; 86: 1001–9. strual cycle. Steroids 1998; 63: 5–13.

J Reproduktionsmed Endokrinol 2010; 7 (Sonderheft 1) 7