Natural conception rates in subfertile couples following fertility awareness training.

PURPOSE: To analyze cumulative pregnancy rates of subfertile couples after fertility awareness training. METHODS: A prospective observational cohort study followed 187 subfertile women, who had received training in self-observation of the fertile phase of the menstrual cycle with the Sensiplan method, for 8 months. The women, aged 21-47 years, had attempted to become pregnant for 3.5 years on average (range 1-8 years) before study entry. Amenorrhea, known tubal occlusion and severe male factor had been excluded. An additional seven women, who had initially been recruited, became pregnant during the cycle immediately prior to Sensiplan training: this is taken to be the spontaneous pregnancy rate per cycle in the cohort in the absence of fertility awareness training. RESULTS: The cumulative pregnancy rate of subfertile couples after fertility awareness training was 38% (95% CI 27-49%; 58 pregnancies) after eight observation months, which is significantly higher than the estimated basic pregnancy rate of 21.6% in untrained couples in the same cohort. For couples who had been seeking to become pregnant for 1-2 years, the pregnancy rate increased to 56% after 8 months. A female age above 35 (cumulative pregnancy rate 25%, p = 0.06), couples who had attempted to become pregnant for more than 2 years (cumulative pregnancy rate 17%, p < 0.01), all significantly reduce the chances of conceiving naturally at some point. CONCLUSIONS: Training women to identify their fertile window in the menstrual cycle seems to be a reasonable first-line therapy in the management of subfertility.

Live birth after artificial oocyte activation using a ready-to-use ionophore: a prospective multicentre study.

Artificial oocyte activation has been proposed as a suitable means to overcome the problem of failed or impaired fertilization after intracytoplasmic sperm injection (ICSI). In a multicentre setting artificial oocyte activation was applied to 101 patients who were diagnosed with fertilization abnormalities (e.g. less than 50% fertilized oocytes) in a previous conventional ICSI cycle. Female gametes were activated for 15 min immediately after ICSI using a ready-to-use Ca(2+)-ionophore solution (A23187). Fertilization, pregnancy and live birth rates were compared with the preceding cycle without activation. The fertilization rate of 48% in the study cycles was significantly higher compared with the 25% in the control cycles (P < 0.001). Further splitting of the historical control group into failed (0%), low (1-30%) and moderate fertilization rate (31-50%) showed that all groups significantly benefitted (P < 0.001) in the ionophore cycle. Fewer patients had their embryo transfer cancelled compared with their previous treatments (1/101 versus 15/101). In total, 99% of the patients had an improved outcome with A23187 application resulting in a 28% live birth rate (35 babies). These data suggest that artificial oocyte activation using a ready-to-use compound is an efficient method.

Strips of Hope: Accuracy of Home Pregnancy Tests and New Developments.

The first home pregnancy test was introduced in 1976. Since then, pregnancy tests have become the most common diagnostic assay used at home. Pregnancy tests use antibodies to detect human chorionic gonadotropin (hCG). It is an ideal marker of pregnancy since it rises rapidly and consistently in early pregnancy and can be detected in urine. The most advanced home pregnancy test currently available assesses the level of hCG found in urine and claims to provide women with reliable results within just a few weeks of pregnancy. Today, over 15 different types of home pregnancy test are available to buy over the counter in Germany. Many tests claim to be highly accurate and capable of detecting pregnancy before the next monthly period is due, although claims such as 8 days prior to menstruation are unrealistic. However, users and healthcare professionals should be aware that, although all are labelled as CE, there are currently no standard criteria for testing performance and claims. This review provides an overview of the development of home pregnancy tests and the data on their efficacy together with an analysis of published data on the accuracy of hCG for the detection of early pregnancy and studies on the use of home-based pregnancy tests. Preliminary data on some home pregnancy tests available in Germany are presented which indicate that many results do not match the claims made in the package insert. Healthcare professionals and women should be aware that some of the claims made for home pregnancy tests are inconsistent and that common definitions and testing criteria are urgently needed.

[Natural fertility in couples and epidemiological aspects of subfertility]. / Natürliche Fertilität eines Paares und epidemiologische Aspekte der Subfertilität.

BACKGROUND: In the last 40 years, fertility rates in Western societies have been declining as a result of lifestyle and generative behavior. AIM: This review summarizes current evidence-based knowledge on natural infertility and epidemiological aspects of subfertility. METHODS: A literature search on natural infertility and epidemiological aspects of subfertility was performed and the available data were structured and put in context. RESULTS: After six unsuccessful cycles, slight or potentially severe subfertility should be assumed. Female age, number of unsuccessful cycles, ovarian reserve, and the results of sperm analysis determine the reproductive potential of a subfertile couple. An early measurement of anti-müllerian hormone levels and a sperm analysis are recommended. CONCLUSIONS: Fertility awareness has gained increasing importance, not only in contraceptive use but also in optimizing individual fertility.

Infertility: definitions and strategies.

Anti-Müllerian hormone is a sensitive marker of ovarian reserve and is suitable for screening. This is important for all women whose age is not critical yet and who not started their "project of family planning". Looking up individual anti-Müllerian hormone levels in percentile normograms inform about the biological clock which might be put back or forward. By this anti-Müllerian hormone supports clinical decisions.

Final ART success rates: a 10 years survey.

BACKGROUND: Cumulative pregnancy rates (CPRs) and live birth rates (CLBRs) are much better indicators of success in IVF programmes than cross-sectional figures per cycle or embryo transfer. They allow a better estimation of patient's chances of having a child and enable comparisons between centres and treatment strategies. METHODS: A 10 year cohort study of patients undergoing their first assisted reproductive technique cycle was conducted. Patients were followed until live birth or discontinuation of treatment. All IVF and ICSI cycles and cryo-cycles with embryos derived from frozen pronuclear stage oocytes were included. The CPR and CLBR were estimated using the Kaplan-Meier method for both the number of treatment cycles and transferred embryos. The analysis assumed that couples who did not return for subsequent treatment cycles would have had the same chance of success as those who had continued treatment. RESULTS: A total of 3011 women treated between 1998 and 2007 were included, and 2068 children were born; women already with a live birth re-entered the analysis as a 'new patient'. For 3394 'patients under observation' with 8048 cycles, the CLBR was 52% after 3 cycles (the median number of cycles per patient), 72% after 6 cycles and 85% after 12 cycles. A CLBR of ∼ 50% was achieved for patients aged under 40 years, after the cumulative transfer of six embryos. The mean live birth rate from one fresh cycle and its subsequent cryo-cycle(s) was 33%. Our analysis also shows that ART can reach natural fertility rates but not exceed them. CONCLUSIONS: Most couples with infertility problems can be treated successfully if they continue treatment. Thereby ART can reach natural fertility rates. Even with the restrictions in place as a result of the German Embryo Protection Law, CLBR reach internationally comparable levels.

Relevance of anti-Mullerian hormone measurement in a routine IVF program.

BACKGROUND: Diminished ovarian reserve has become a major cause of infertility. Anti-Mullerian hormone (AMH) seems to be a promising candidate to assess ovarian reserve and predict the response to controlled ovarian hyperstimulation (COH). This prospective study was conducted to evaluate the relevance of AMH in a routine IVF program. METHODS: Three hundred and sixteen patients were prospectively enrolled to enter their first IVF/ICSI-cycle. Age, FSH-, inhibin B- and AMH-levels and their predictive values for ovarian response and clinical pregnancy rate were compared by discriminant analyses. RESULTS: A total of 132 oocyte retrievals were performed. A calculated cut-off level < or =1.26 ng/ml AMH alone detected poor responders (< or =4 oocytes) with a sensitivity of 97%, and there was a 98% correct prediction of normal response in COH if levels were above this threshold. With levels <0.5 ng/ml, a correct prediction of very poor response (< or =2 oocytes) was possible in 88% of cases. Levels of AMH > or =0.5 ng/ml were not significantly correlated with clinical pregnancy rates. CONCLUSIONS: AMH is a predictor of ovarian response and suitable for screening. Levels < or =1.26 ng/ml are highly predictive of reduced ovarian reserve and should be confirmed by a second line antral follicle count. Measurement of AMH supports clinical decisions, but alone it is not a suitable predictor of IVF success.

The effectiveness of a fertility awareness based method to avoid pregnancy in relation to a couple's sexual behaviour during the fertile time: a prospective longitudinal study.

BACKGROUND: The efficacy of fertility awareness based (FAB) methods of family planning is critically reviewed. The objective was to investigate the efficacy and the acceptability of the symptothermal method (STM), an FAB method that uses two indicators of fertility, temperature and cervical secretions observation. This paper will recommend a more suitable approach to measure the efficacy. METHODS: Since 1985, an ongoing prospective observational longitudinal cohort study has been conducted in Germany. Women are asked to submit their menstrual cycle charts that record daily basal body temperature, cervical secretion observations and sexual behaviour. A cohort of 900 women contributed 17,638 cycles that met the inclusion criteria for the effectiveness study. The overall rates of unintended pregnancies and dropout rates have been estimated with survival curves according to the Kaplan-Meier method. In order to estimate the true method effectiveness, the pregnancy rates have been calculated in relation to sexual behaviour using the 'perfect/imperfect-use' model of Trussell and Grummer-Strawn. RESULTS: After 13 cycles, 1.8 per 100 women of the cohort experienced an unintended pregnancy; 9.2 per 100 women dropped out because of dissatisfaction with the method; the pregnancy rate was 0.6 per 100 women and per 13 cycles when there was no unprotected intercourse in the fertile time. CONCLUSIONS: The STM is a highly effective family planning method, provided the appropriate guidelines are consistently adhered to.

Determination of the fertile window: reproductive competence of women--European cycle databases.

OBJECTIVES: The objective of the present paper is to review the main results of recent European cycle databases on ovulation detection and determination of the fertile window performed by the women themselves. METHODS: The ongoing German Long-term Cycle Database currently comprises 32788 prospectively collected cycle charts of 1551 women, the I European Cycle Database (10 countries) 1328 women/19048 cycles, the II European Cycle Database (six countries) 782 women/6724 cycles, and the World Health Organization Database (one European country) 234 women/2808 cycles. The women record cycle parameters (cervical mucus changes, temperature rise, etc.), family planning intention and sexual behavior. RESULTS: With the symptothermal method of natural family planning it has become possible to determine the fertile window in order to avoid pregnancy with a method effectiveness of 0.3%. According to a small sub-study, the ovulation time observed by the women themselves correlates closely with ovulation detected by ultrasound and measurement of luteinizing hormone (correlation within 1 day in 89% of the 62 cycles). Fertility awareness methods can be integrated into the management of sub-fertility. They seem to shorten the time to pregnancy. CONCLUSIONS: Self-observation of the fertile window puts women into a position to develop a high level of reproductive competence that could be used much more in different areas than is currently the case.

Definition and prevalence of subfertility and infertility.

A common definition of sub- and infertility is very important for the appropriate management of infertility. Subfertility generally describes any form of reduced fertility with prolonged time of unwanted non-conception. Infertility may be used synonymously with sterility with only sporadically occurring spontaneous pregnancies. The major factor affecting the individual spontaneous pregnancy prospect is the time of unwanted non-conception which determines the grading of subfertility. Most of the pregnancies occur in the first six cycles with intercourse in the fertile phase (80%). After that, serious subfertility must be assumed in every second couple (10%) although--after 12 unsuccessful cycles--untreated live birth rates among them will reach nearly 55% in the next 36 months. Thereafter (48 months), approximately 5% of the couples are definitive infertile with a nearly zero chance of becoming spontaneously pregnant in the future. With age, cumulative probabilities of conception decline because heterogeneity in fecundity increases due to a higher proportion of infertile couples. In truly fertile couples cumulative probabilities of conception are probably age independent. Under appropriate circumstances a basic infertility work-up after six unsuccessful cycles with fertility-focused intercourse will identify couples with significant infertility problems to avoid both infertility under- and over-treatment, regardless of age: Couples with a reasonably good prognosis (e.g. unexplained infertility) may be encouraged to wait because even with treatment they do not have a better chance of conceiving. The others may benefit from an early resort to assisted reproduction treatment.

Time to pregnancy: results of the German prospective study and impact on the management of infertility.

BACKGROUND: The likelihood of spontaneous conception in subsequent cycles is important for a balanced management of infertility. Previous studies on time to pregnancy are mostly retrospective and biased because of exclusion of truly infertile couples. The study aim was to present a non-parametric estimation of cumulative probabilities of conception (CPC) in natural family planning (NFP) users illustrating an ideal of human fertility potential. METHODS: A total of 346 women was observed who used NFP methods to conceive from their first cycle onwards. The couples practising NFP make optimal use of their fertility potential by timed intercourse. The CPC were estimated for the total group and for couples who finally conceived by calculating Kaplan-Meier survival rates. RESULTS: A total of 310 pregnancies occurred among the 346 women; the remaining 36 women (10.4%) did not conceive. Estimated CPC for the total group (n = 340 women) at one, three, six and 12 cycle(s) were 38, 68, 81 and 92% respectively. For those who finally conceived (truly fertile couples, n = 304 women), the respective pregnancy rates were 42, 75, 88 and 98% respectively. Although the numbers of couples in both groups were similar, the impact of age on time to conception, as judged by the Wilcoxon test, was less in the truly fertile than in the total group. CONCLUSIONS: Most couples conceive within six cycles with timed intercourse. Thereafter, every second couple is probably either subfertile or infertile. CPC decline with age because heterogeneity in fecundity increases. In the subgroup of truly fertile couples, an age-dependent decline in CPC is statistically less obvious because of high homogeneity, even with advancing age.

Cycle characteristics after discontinuation of oral contraceptives.

Nearly 60% of the women between 20 and 40 years of age who do not want to conceive choose oral contraceptives (OCs) for contraception in Germany. In an ongoing prospective study on the use of natural family planning in Germany, 175 women have been observed for 3,048 cycles immediately after having discontinued OCs (post-pill group). They were compared to a control group of 284 women observed for 6,251 cycles, who had never taken OCs. Both groups were comparable in age and sociodemographic characteristics. After discontinuing OCs, 57.9% of all first cycles were ovulatory with sufficient luteal phases. However, for the total post-pill group the cycle length was significantly prolonged up to the ninth cycle. A significantly higher number of luteal phases were insufficient in the post-pill group. Major cycle disturbances (cycle length > 35 days or luteal phase of < 10 days of elevated basal body temperature or anovulatory cycles) were significantly more frequent in the post-pill group up to the seventh cycle. Cycle disturbances after discontinuing OCs were reversible but the time of regeneration took up to 9 months (significant) or even longer (not significant). These results will help to counsel couples who wish to conceive after discontinuing OCs or who want to continue contraception with alternative methods.

Research and quality control in natural family planning with relational database systems.

Research and quality control in natural family planning (NFP) is based on continuous data collection in prospective studies. The quality of the data is determined by the reliability of collection, input, management, and retrieval. During a period of ten years, different relational databases were programmed to manage the large number of very different data in NFP studies. Recently, all experience with different database systems has been summarized by writing and testing a completely new data management system based on MS Access 97: NFPDAT 1.0. This new software is used for data collection, evaluation and administration in NFP Study Groups. Over 200 internal formulae guarantee maximum data consistency while 30,000 cycles from 1477 patients were stored. Easy data evaluation for research and administration is possible with the help of a new report generator even without prior knowledge of SQL (System Query Language) or Visual Basic for MS Access 97. Using this method, interim results for research and quality control can be obtained at any time. NFPDAT can be used by all Natural Family Planning Study Groups using the symptothermal method for research and administration. With the help of NFPDAT, various prospective studies of Natural Family Planning were conducted.

Effects of add-back therapy on bone mineral density and pyridinium crosslinks in patients with endometriosis treated with gonadotropin-releasing hormone agonists.

Treatment of endometriosis with gonadotropin-releasing hormone agonists (GnRHa) is limited to 6 months because of possible adverse effects on bone metabolism. We designed a randomized, double-blind, placebo-controlled, prospective study of 27 patients with endometriosis who were given GnRHa with or without hormone add-back therapy (+ 20 microg of ethinyl estradiol with 0.15 mg desogestrel) designed to suppress the adverse effects of hypoestrogenism while preserving the efficacy of GnRHa. Both regimens showed significant improvements in endometriosis, dysmenorrhea, and pelvic pain; effects were significantly better in the GnRHa + placebo group. The GnRHa + placebo group had significantly higher serum calcium levels and a significantly higher loss of lumbar spine bone mineral density (BMD). Urinary levels of pyridinium crosslinks increased significantly in the GnRHa + placebo group, and declined to normal in the GnRHa + add-back group. The add-back therapy protects women taking GnRHas from severe loss of BMD and accelerated bone collagen resorption, but reduces the efficacy of the GnRHa.

Steroidal 'add-back' therapy in patients treated with GnRH agonists.

GnRH analogues (GnRH-a) are well established in the treatment of endometriosis. However, due to hypooestrogenic effects, treatment is limited to 6 months. The aim of this randomized, double-blind, comparative study was to evaluate whether symptoms and signs of hypooestrogenism, e.g. hot flushes, sweating and sleeplessness, could be avoided by a steroidal add-back regimen, while the beneficial effect of a GnRH-a on endometriosis could be maintained. In group A, 14 patients were treated with 3.75 mg leuprorelin acetate depot per month i.m. in combination with 20 mg ethinyloestradiol plus 0.15 mg desogestrel orally for 3 weeks. In group P, 13 patients received leuprorelin acetate, following the same schedule as in group A, and placebo. Treatment duration was 6 months. At first-look laparoscopy (postoperatively) group A had an r-AFS score of 23.57 and group P of 24.23. After 6 months of treatment with leuprorelin acetate depot r-AFS scores had dropped to 16.14 in group A and to 6.25 in group P at second-look laparoscopy, achieving statistical significance in both groups (p < 0.001). Hypooestrogenic adverse drug reactions (e.g. hot flushes, sweating and sleeplessness) were more frequently reported in group P, whereas the occurrence of headache was comparable in both groups. Dysmenorrhoea was significantly reduced in both groups, whereas dyspareunia was only decreased in group P. Variations in laboratory values were within normal ranges and did not give any concern about drug safety. Loss of bone mineral density caused by the GnRH-a was reduced by the combined oestrogen/progestin add-back therapy. In conclusion, this therapy can lead to a reduction in hypooestrogenic adverse drug reactions and mostly preserves agonist efficacy with the chance of treatment prolongation.

Natural family planning with and without barrier method use in the fertile phase: efficacy in relation to sexual behavior: a German prospective long-term study.

A large prospective long-term study with users of natural family planning (NFP) methods has been conducted to analyze the relation between unintended pregnancy rates and sexual behavior with special reference to barrier method use in the fertile phase. Seven hundred and fifty eight NFP beginners, 19-45 years of age, 14870 cycles, 28 unintended pregnancies were studied. Of the couples, 54.2% use NFP only or predominantly and 45.9% use mixed methods (additional barrier method use in the fertile phase in 55.7% of the cycles). The overall pregnancy rate after 12 cycles of exposure is 2.2% according to the actuarial method. There is no significant difference between NFP users and mixed methods users and also no significant effect of duration of use in the first 5 years of exposure. During "perfect use" the pregnancy rate at 12 months is 0.63%. When only protected intercourse takes place in the fertile phase the pregnancy rate is 0.45%. The symptothermal method of NFP is most unforgiving for imperfect use (unprotected intercourse in the fertile phase). However, it is extremely effective when either abstinence or protected intercourse is used in the fertile phase.

[How do self-observed cycle symptoms correlate with ovulation?]. / Wie korrelieren selbstbeobachtete Zyklussymptome mit der Ovulation?

The symptoms of self-observation of the menstrual cycle (basal body temperature, mucus symptom, autopalpation of the cervix) are often regarded as not reliable for ovulation detection. In a prospective study 87 NFP cycles are monitored additionally with ultrasound and LH tests to calculate the correlation of the ovulation-time with the symptoms of self-observation. Our results show that the symptoms of self-observation allow a reliable detection of the time of ovulation. Only a short introduction into the method of self-observation is a necessary precondition. The reliable detection of ovulation gives the opportunity of cycle analysis of large groups especially in long time investigations. In this way a large set of valuable and reliable data on normal and disturbed menstrual cycles will be available.

Sexual behavior of natural family planning users in Germany and its changes over time.

For 10 years, a prospective study has been taking place in Germany to examine the use of natural family planning (NFP). As natural methods are behavioral methods, use-effectiveness, acceptability and continuation rates are very much influenced by patterns of sexual behavior. Therefore we performed an analysis of the sexual behavior of NFP users. Out of the data base of 1211 clients and 12,591 cycles we could identify a group of 300 women, all NFP beginners, with 5900 contraceptive cycles, who contributed at least 12 cycles with reliable recording of their sexual activity. Different groups were analyzed with methods of analysis of variance and regression models to find out significant differences in their sexual behavior with respect to sociodemographic structure and time of use. Nearly half of all the women systematically combine the fertility awareness part of NFP with other family planning methods. They use barriers in more than 60% of their cycles. The other half never or only in about 7% of their cycles use additional barrier methods. The latter show a clear decrease in barrier use in the course of time, whereas the frequent barrier users constantly combine the advantages of two family planning methods. Regarding the frequency of intercourse they are the sexually more active ones and show distinct sociodemographic characteristics. We could confirm the existence of three groups of NFP users, which differ significantly in their use of NFP as a family planning method. Despite these differences the low pregnancy rates indicate the conscious and risk-related sexual behavior of the group members.