Human Reproduction (Oxford, England), 31(2), 445-453, 2015
Monitoring of ovarian activity by measurement of urinary excretion rates using the Ovarian Monitor, Part IV: the relationship of the pregnanediol glucuronide threshold to basal body temperature and cervical mucus as markers for the beginning of the post-ovulatory infertile period
Pilar Vigil, Mario Festin, Simon Brown
Delwyn G Cooke, María Elena Alliende , Leonard F Blackwell
Do the basal body temperature (BBT) shift and the cervical mucus markers for the beginning of the post-ovulatory infertile phase (POIP) of a menstrual cycle agree with the corresponding urinary pregnanediol glucuronide (PdG) threshold value?
Summary Answer
Perfect agreement between the cervical mucus markers and BBT shift and the hormonal definition of the start of post-ovulatory infertility occurred for only 7-17% of the cycles.
What Is Known Already
The PdG threshold of 7.0 µmol/24 h is an objective and accurate marker for the beginning of the POIP. The rise in serum progesterone also produces the BBT shift and changes in cervical mucus which determine the mucus peak. Serum progesterone and urinary PdG are closely correlated when variations in urine volume are taken into account.
Study Design, Size, Duration
Individual menstrual cycle profiles of urinary PdG excretion rates for 91 fertile cycles from normally cycling women were analysed to identify the day of the beginning of the POIP. These days were compared with those determined by the day of the BBT shift +2 days, the day of the mucus peak +4 days and the later of these two indicators. The study lasted 3 years.
Participants/Materials, Setting, Methods
A total of 62 women with normal menstrual cycles were recruited from three centres: Palmerston North, New Zealand; Sydney, Australia and Santiago, Chile. The cycles were displayed individually in a proprietary database program which recorded the PdG excretion rates, the BBT shift day and the cervical mucus peak day. A group of 15 women from a separate Chilean study had PdG urinary data measured as well as their day of ovulation determined by ultrasound.
MAIN RESULTS AND THE ROLE OF CHANCE: The BBT and cervical mucus markers differed significantly in their identification of the beginning of the POIP when compared with the PdG excretion rate of 7.0 µmol/24 h. The observation that the BBT shift day and the mucus peak day could be identified even though the PdG excretion rates were still at baseline levels in some cycles could lead to an unexpected pregnancy for women using these natural family planning (NFP) indicators.
Limitations, Reasons for Caution
The study consisted only of fertile cycles from women with regular cycles of 20-40 days duration. All the women were intending to avoid a pregnancy during the study, thus the limits of the fertile window were not tested.
Wider Implications of the Findings
The NFP signals occurring earlier than the PdG threshold day could lead to an unexpected pregnancy. The signals occurring on the same day or later than the PdG threshold would not lead to unexpected pregnancies, but would require extra abstinence that could lead to non-compliance with the NFP method. A possible improvement in reliability of NFP methods is suggested.
Study Funding/Competing Interests
This study (project #90905) was funded by the NDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP). D.G.C. currently works for a diagnostic development company, Science Haven Ltd. The other authors have nothing to declare.
PMID 26677961 26677961 DOI 10.1093/humrep/dev303 10.1093/humrep/dev303
Cite this article
Blackwell, L. F., Vigil, P., Alliende, M. E., Brown, S., Festin, M., & Cooke, D. G. (2016). Monitoring of ovarian activity by measurement of urinary excretion rates using the Ovarian Monitor, Part IV: the relationship of the pregnanediol glucuronide threshold to basal body temperature and cervical mucus as markers for the beginning of the post-ovulatory infertile period. Human reproduction (Oxford, England), 31(2), 445-453. https://doi.org/10.1093/humrep/dev303
Blackwell LF, Vigil P, Alliende ME, Brown S, Festin M, Cooke DG. Monitoring of ovarian activity by measurement of urinary excretion rates using the Ovarian Monitor, Part IV: the relationship of the pregnanediol glucuronide threshold to basal body temperature and cervical mucus as markers for the beginning of the post-ovulatory infertile period. Hum Reprod. 2016;31(2):445-453. doi:10.1093/humrep/dev303
Blackwell, L. F., et al. "Monitoring of ovarian activity by measurement of urinary excretion rates using the Ovarian Monitor, Part IV: the relationship of the pregnanediol glucuronide threshold to basal body temperature and cervical mucus as markers for the beginning of the post-ovulatory infertile period." Human reproduction (Oxford, England), vol. 31, no. 2, 2016, pp. 445-453.
There is considerable individual day-to-day variation within the menstrual cycle and between cycles in women. Average hormone curves inadequately describe the individual hormone patterns experienced by women. The present study applies a novel application of a statistical array (heat map) to demonstrate both individual and group menstrual cycle hormone variability.
Using pre-existing datasets, two cohorts of women were analysed using a statistical method to visualise quantitative hormonal variation. In one cohort, 107 women contributed a total of 283 menstrual cycles and in the second cohort, 21 women contributed a total of 62 menstrual cycles. Women collected first morning urine samples for analysis of estrone-3-glucuronide (E1G) and luteinizing hormone (LH) in both datasets. In the larger dataset, pregnanediol-3-alpha-glucuronide (PDG) and follicle-stimulating hormone (FSH) were also collected. Serial ultrasounds identified the precise day of ovulation in the larger dataset. In the smaller dataset, peak LH was used to identify the estimated day of ovulation.
The main outcome measure was identifying hormonal variability using hormone array heat maps. Heat maps were able to quickly show clustering of hormone patterns in the fertile window and on the day of ovulation. Individual differences were identified in rows on the heat map relative to the day of ovulation. This new tool to visually represent hormonal changes with heat maps identifies both individual and group variability of menstrual cycle hormones.
Fertility AwarenessUrinary Hormone MonitoringHormone ValidationHome Hormone Testing
Open Access
Bouchard TP et al., 2025·Womens Health Rep (New Rochelle)
Measuring quantitative menstrual cycle hormones at home may help women better understand their postpartum and perimenopause fertility transitions, but these quantitative fertility monitors require validation. This study included 16 North American women, aged 28-51, during either the postpartum (n = 8, cycles = 18) or perimenopause (n = 8, cycles = 35) fertility transitions testing daily first-morning urine testing with both the Mira Monitor and ClearBlue Fertility Monitor (CBFM) along with menstrual cycle parameter tracking. The main outcome measures were a rise in estrone-3-glucuronide (E13G) and luteinizing hormone (LH) urine hormone values from the Mira monitor correlated to low, high, or peak values on the CBFM. Both in the postpartum and perimenopause transitions, the identification of the day of ovulation based on the LH surge on the Mira and CBFM monitors was highly correlated (R = 0.94 and 0.83, p < 0.001). The E13G levels on the Mira monitor were significantly higher for a CBFM reading of "High" compared with "Low" for both the postpartum and perimenopausal cycles (all p < 0.001). Similarly, the LH levels on the Mira monitor were significantly higher for a CBFM reading of "Peak" (LH surge) compared with "High" for both the postpartum and perimenopausal cycles (all p < 0.001). The LH surge and levels of E13G in urine identified on the quantitative Mira fertility monitor strongly correlate to the LH surge and the shift from low to high on the CBFM during the postpartum and perimenopause transitions.
Perimenopause/MenopauseHormone TrackingUrinary Hormone MonitoringPerimenopause
Open Access
The fertility tracking of menstrual cycles during perimenopause with a quantitative hormone monitor is a novel undertaking. Women in regular menstrual cycles have been tracking their fertility using different biomarkers since the 1960's. Presently, there are newer electronic hormonal devices used to track fertility that provide more exact and objective data to help delineate the fertile time frame of a woman's cycle. These devices measure quantitative levels of estrogen, the luteinizing hormone, progesterone, and follicle-stimulating hormone, all of which occur at varying levels during the menstrual cycle. As women advance toward menopause, their cycles vary in length, and their hormones fluctuate. In this retrospective analysis, forty-two women aged 40 to 50 tracked their cycles over time, and eight of these forty-two women used the quantitative hormonal device. With the use of this device, the perimenopausal period has revealed distinct hormonal cycle characteristics that are unique to this group of women. It is the purpose of this paper to discuss these cycle's characteristics during perimenopause, which were found with the use of the quantitative hormonal device.
InfertilityFrozen Embryo TransferPreeclampsia Risk FactorsPAPP-A and IGF-1
Mørch NF et al., 2026·Human reproduction (Oxford, England)
Are maternal concentrations of pregnancy-associated plasma protein-A (PAPP-A) and insulin-like growth factor-1 (IGF-1) influenced by the frozen embryo transfer (FET) protocol in early pregnancy? Maternal concentrations of PAPP-A and IGF-1 were significantly lower in programmed cycle (PC) FET compared to modified natural cycle (mNC) FET among ovulatory women and compared to gonadotrophin-stimulated cycle (gSC) FET in anovulatory women. PC-FET has been associated with increased risks of preeclampsia and other placenta-related complications, pointing to altered placental development. PAPP-A and IGF-1 are biochemical markers of early placental function, and reduced levels have been linked to preeclampsia and other adverse outcomes. These markers may therefore provide insight into the pathways underlying the distinct risk profile of PC-FET. STUDY DESIGN, SIZE, This is a secondary analysis from a randomized controlled trial investigating estradiol and progesterone concentrations in FET treatments. The trial was conducted at Copenhagen University Hospital-Herlev, Denmark, from April 2021 to December 2024. Biochemical analyses for PAPP-A and IGF-1 were performed on stored biobank samples from the trial. The main analyses included women with ongoing pregnancies (n = 116), while additional analyses of IGF-1 were conducted in all ovulatory women with available biobank samples (n = 193). PARTICIPANTS/MATERIALS, SETTING, Eligible participants were women aged 18-40 years with BMI ≤35 kg/m2 undergoing frozen-thawed autologous blastocyst transfer. Ovulatory women were randomized to mNC or PC, and anovulatory women to gSC or PC. Samples were collected at the following 7 timepoints on the 2nd or 3rd day of menstrual bleeding, on the day of trigger/endometrial thickness ≥7 mm, on the day of embryo transfer and by gestational ages (GA) 4 + 2, 6 + 0, 8 + 0, and 9 + 6. Data on placental weight were collected at delivery. MAIN The present analyses included women with ongoing pregnancies 43 in the ovulatory mNC group, 42 in the ovulatory PC group, 16 in the anovulatory gSC group, and 15 in the anovulatory PC group. PC had substantially lower IGF-1 concentrations from treatment initiation through GA 8 + 0 compared to both mNC and gSC. Ovulatory women treated with PC showed significantly lower PAPP-A concentrations during endometrial preparation (7.4 vs 8.7 mU/l; adjusted P = 0.02), at embryo transfer (6.7 vs 8.8 mU/l; adjusted P < 0.001), and GA 4 + 2 (7.2 vs 8.5 mU/l; adjusted P = 0.03) than women treated with mNC. Among anovulatory women, PAPP-A concentrations were also reduced during endometrial preparation (5.8 vs 9.1 mU/l; adjusted P = 0.008) in PC compared to gSC. LIMITATIONS, As this was a secondary analysis, no formal power calculation was made, and statistical power may therefore be limited. We provide evidence that PC-FET was followed by lower IGF-1 concentrations in early pregnancy and by time-dependent reductions in PAPP-A compared to mNC-FET and gSC-FET. These findings suggest alterations in early placental biology that may contribute to the adverse obstetric risk profile associated with PC-FET. Future studies should clarify whether these changes are related to the use of oral estradiol and whether alternative administration routes could modify this risk. STUDY FUNDING/COMPETING INTEREST(S): The trial was funded by Gedeon Richter Nordics AB, including analysis of biobank samples (grant numbers DK-2019-04, DK-2022-03, DK-2023-08, DK-2023-06, DK-2024-08). The trial also received one grant from the Gangsted-Rasmussen Foundation (grant number A39784) and a grant was obtained from the local research board at Copenhagen University Hospital-Herlev. The study was designed and planned independently, with no involvement from the funders in data analysis or interpretation of the results. N.F.M. has received funding for congress attendance from Gedeon Richter Nordics AB and Merck A/S, unrelated to the present work. B.N. has received grants to the institution from Merck A/S, Gedeon Richter Nordics AB, and Ferring Pharmaceuticals A/S, along with personal fees from Ferring Pharmaceuticals A/S, travel support from Gedeon Richter Nordics AB, and has participated in a data safety monitoring or advisory board for Ferring Pharmaceuticals A/S, outside of this research. M.K. has received funding from Rigshospitalets Research Board outside of this research. L.R. has received a research grant from the Novo Nordisk Foundation outside of this research. P.F.S. has received grants from Merck A/S, Gedeon Richter Nordics AB, and Ferring Pharmaceuticals A/S, travel support from Ferring Pharmaceuticals A/S, and personal fees from Novo Nordisk for webinars, outside of this study. 2020-001218-39 in EudraCT.