Baseline Levels of Serum Progesterone and the First Trimester Pregnancy Outcome in Women with Threatened Abortion: A Retrospective Cohort Study

Deng, Yongshi; Chen, Chi; Chen, Siyun; Mai, Guanyan; Liao, Xiuping; Tian, He; Liu, Wenli; Ji, Shuling; Liu, Ying; Gao, Jie; Luo, Songping

doi:https://doi.org/10.1155/2020/8780253

BioMed Research International

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Abstract Introduction Materials and Methods Results Discussion Conclusions Conflicts of Interest Authors’ Contributions Acknowledgments Supplementary Materials References Copyright Related Articles

Research Article | Open Access

Volume 2020 | Article ID 8780253 | https://doi.org/10.1155/2020/8780253

Baseline Levels of Serum Progesterone and the First Trimester Pregnancy Outcome in Women with Threatened Abortion: A Retrospective Cohort Study

Yongshi Deng,¹Chi Chen,²Siyun Chen,¹Guanyan Mai,¹Xiuping Liao,¹He Tian,¹Wenli Liu,¹Shuling Ji,¹Ying Liu,¹Jie Gao,³and Songping Luo³

Academic Editor: Jose Guilherme Cecatti

Received02 Sept 2019

Revised18 Dec 2019

Accepted30 Jan 2020

Published03 Mar 2020

Abstract

Objective. The relationship between serum progesterone and the first trimester pregnancy outcome of threatened abortion is still controversial. Therefore, we aimed to further study the association between these two parameters. Methods. The present study is an observational retrospective cohort study. A total of 726 participants who had threatened abortion from a hospital in Guangdong, China, were included in this study from 17th August 2011 to 30th October 2018. The exposure variable and the outcome variable were serum progesterone measured at baseline and early pregnancy outcome, respectively. Covariates involved in this study included patients’ basic demographics, obstetric history, and clinical information. Results. A negative association and a saturation effect were detected between serum progesterone and the first trimester pregnancy outcome. When progesterone <90.62 nmol/L, an increase in 1 nmol/L of serum progesterone was associated with 3% decrease of the risk of miscarriage (OR: 0.97, 95% CI: 0.95-0.98). Conclusion. There was a greater risk of abortion when the serum progesterone level was less than 90.62 nmol/L. Our findings can better assist the clinician in understanding patients’ conditions and making medical decisions.

1. Introduction

Threatened abortion is defined as vaginal bleeding through a closed cervical os, with or without abdominal pain, during the first 20 weeks of pregnancy [1]. Threatened abortion may be one of the most common gynecological conditions and occurs in 25% of pregnancies [2]. Unfortunately, about 10% to 20% of the women who have threatened abortion may experience a miscarriage [2], which may cause depression, anxiety, and even posttraumatic stress symptoms [3].

Progesterone is a sex steroid which plays an important role in women’s menstrual cycles and pregnancy [4, 5]. It can induce endometrium change into the secretory phase, preparing for fertilized egg implantation [4]. In terms of immunity, it can regulate the balance of cytokines and influence the activity of natural killer cells [5, 6]. It suppresses uterine contraction, by enhancing nitric oxide production in the lining of the uterus [7, 8]. Furthermore, progesterone may reduce the spiral arteries’ pulsatility index and resistance index; thus, it can increase uteroplacental circulation [9].

Several studies showed that low serum progesterone was associated with abortion [10–14]. Hence, exogenous progesterone supplements were often used to treat threatened abortion, especially in China [15]. However, the efficacy of progesterone is controversial [16–19], and the applicable standard is still vague [15, 16]. In this study, we aim to further analyse the relationship between serum progesterone and the first trimester pregnancy outcome.

2. Materials and Methods

2.1. Study Participants

This study is a retrospective cohort study conducted at the First Affiliated Hospital of Guangzhou University of Chinese Medicine. The clinical information of women with threatened abortion from the hospital’s electronic medical record system was collected from 17th August 2011 to 30th October 2018. There was no sample size calculation. For convenience, the sample size of this study was based on previous similar studies [20–24]. A total of 1848 threatened abortion patients were initially included. After screening, 726 cases were available for data analysis (see Figure 1 for details).

The inclusion criteria were intrauterine pregnancy with pregnancy-related vaginal bleeding [1] between 4 and 12 weeks of gestation. For all patients, the gestational age was calculated from the date of last menstruation.

The exclusion criteria were as follows: (1) Patients developed vaginal bleeding because of other reasons rather than threatened abortion. (2) Patients who were pregnant through assisted reproductive technology. (3) Patients were diagnosed as missed abortion or inevitable miscarriage at admission. (4) Patients eventually were diagnosed with ectopic pregnancy. (5) Patients without baseline ultrasound. (6) Patients who had been using progesterone before inclusion in the study.

2.2. Exposure Variable

The first measurement of serum progesterone was made on the second day after admission. Doctors determined the next hormone measurement time based on the patient’s condition, normally between 3 and 7 days after the first measurement.

2.3. Outcome Variable

Our primary outcome was spontaneous miscarriage at the first trimester, including inevitable abortion, incomplete abortion, complete abortion, and missed abortion. The diagnosis of miscarriage was made by a clinician; they must be based on the patient’s symptoms, signs, serum β-HCG, serum progesterone, and ultrasound. The follow-up consultation by telephone was made at 13 weeks of gestation.

2.4. Covariates

The selection of covariates in this study was mainly based on previous studies which researched the relationship between progesterone and pregnancy outcome [10–14, 17–22]. Therefore, patients’ basic demographics (age, height, weight, smoking history, drinking history, and marital status), obstetric history (times of gestity, parity, and abortion), and clinical information (gestational week, progesterone, β-HCG, medical history, and use of progesterone) were collected. We compiled patients’ basic demographics, obstetric history, and partial clinical information at the time of enrollment. The first measurement of serum β-HCG was on the second day after admission, and the measurement interval was 3-7 days. Log10 transformation of β-HCG was used to reduce the skewness of its data distribution. We obtained medication information through medical records.

2.5. Treatment

Progestogen preparations used in our hospital included dydrogesterone tablets, progesterone injections, and progesterone capsules. The type and dose of progestogen were selected based on the patient’s symptoms, auxiliary examinations, and medical history, followed the Luteal Support and Progesterone Supplementation Consensus of the Chinese Medical Association Reproductive Medicine Branch [15].

2.6. Statistical Methods

Categorical variables were shown in frequency or percentage. Continuous variables were expressed in (SD) when they had normal distribution. Continuous variables were expressed in median with quartile when they had skewed distribution. To investigate whether baseline levels of serum progesterone was correlated with the first trimester pregnancy outcome in threatened abortion women, our statistical analysis included three main steps.

Step 1: we used chi-square test (categorical variables), Student -test (normal distribution), or Mann-Whitney test (skewed distribution) to calculate the difference of baseline characteristics for patients with different pregnancy outcome in Table 1. The first measurement of serum progesterone and β-HCG was reported.

Step 2: binary logistic regression and marginal structural model were used for multivariate analysis. Three models were constructed in Table 2: model 1, binary logistic regression without adjusted covariates, used the first measurement of serum progesterone; model 2, binary logistic regression adjusted all covariates presented in Table 1, used the first measurement of serum progesterone and β-HCG; and model 3, marginal structural model adjusted all covariates in Table 1, used the serial measurements of serum progesterone and β-HCG.

To ensure the robustness of data analysis, we made a sensitivity analysis. (1) Serum progesterone changed over time [11] and had two-way causality with progesterone therapy. Therefore, we used marginal structural model for sensitivity analysis. (2) In order to verify the results of progesterone as the continuous variable, and to examine the possibility of nonlinearity, we converted basal progesterone into a categorical variable according to the tertile; we also performed an interaction test and calculated the for trend.

Step 3: to research the nonlinearity relationship of basal progesterone and early pregnancy outcomes, a binary logistic regression and smooth curve fitting (penalized spline method) were conducted in Table 3 and Figure 2. If nonlinearity was detected, we used both binary logistic regression and two-piecewise binary logistic regression to fit the association and selected the best fit model based on for the log-likelihood ratio test. Then, we calculated the inflection point using recursive algorithm and constructed a two-piecewise linear regression model on both sides of the inflection point.

All the analyses were performed with the statistical software packages R (http://www.R-project.org, The R Foundation) and EmpowerStats (http://empowerstats.com, X&Y Solutions, Inc., Boston, MA). values less than 0.05 (two-sided) were considered statistically significant.

2.7. Ethics

This study was approved by the ethical review board of the First Affiliated Hospital of Guangzhou University of Chinese Medicine.

3. Results

3.1. Study Participants

After screening, according to inclusion criteria and exclusion criteria (see Figure 1 for details), 726 of participants were finally adopted in statistics, including 28.65% (208 of 726 patients) miscarriage and 71.35% (518 of 726 patients) ongoing pregnancy within 12 weeks of gestation.

As shown in Table 1, compared with continue pregnancy patients, participants in the miscarriage group had higher maternal age, higher gestity, lower basal progesterone, lower basal β-HCG (log10), lower embryo visualized rate, and lower cardiac movement visualized rate.

3.2. Multivariate Analysis

In this research, we constructed three models to observe the relationship between serum progesterone and early pregnancy outcome. The odds ratio (OR) and 95% confidence intervals (CI) are listed in Table 2. The model-based effect size can explain the difference between every one unit of serum progesterone and the association with the risk of miscarriage.

In model 1 (nonadjusted model), an increase in 1 nmol/L of basal serum progesterone was associated with 2% decrease of the risk of miscarriage (OR: 0.98, 95% CI: 0.98-0.99). In model 2 (fully adjusted model), the basal progesterone increased by 1 nmol/L and the risk of miscarriage decreased by 1% (OR: 0.99, 95% CI: 0.98-0.99). In model 3 (marginal structural model), 1 nmol/L increase of serial progesterone was also associated with 1% decrease of the risk of miscarriage (HR: 0.99, 95% CI: 0.98-0.99). This suggested that the results were stable and baseline serum progesterone can be used as an exposure factor to discuss its relationship with pregnancy outcomes. Besides, we found that the trend of the ORs in different basal progesterone groups was nonequidistant, which meant nonlinearity existed.

3.3. Nonlinearity Analysis

By using binary logistic regression and the penalty curve method, we found the nonlinear relationship between baseline serum progesterone and the risk of abortion to be within 12 weeks (Table 3 and Figure 2).

By recursive algorithm, we got the inflection point of 90.62 nmol/L. When basal serum progesterone was <90.62 nmol/L, an increase in 1 nmol/L of progesterone was associated with 3% decrease of the risk of miscarriage (OR: 0.97, 95% CI: 0.95-0.98). When basal serum progesterone was >90.62 nmol/L, the increase in progesterone did not affect the pregnancy outcome (OR: 1.01, 95% CI: 0.99-1.02). This result indicated that there was a saturation effect on the relationship between baseline serum progesterone and early pregnancy outcome. When basal serum progesterone was <90.62 nmol/L, the risk of miscarriage decreased with the rise of progesterone. When basal serum progesterone was >90.62 nmol/L, the risk of miscarriage would not decrease even if progesterone was elevated.

4. Discussion

Our study was aimed at investigating the relationship between serum progesterone levels and pregnancy outcome within 12 weeks of gestation in threatened abortion women. The results showed that basal serum progesterone had a negative association with the risk of the first trimester abortion; even the effects of time and progesterone therapy were considered. In addition, we found a saturation effect between basal serum progesterone and the first trimester abortion risk. Their negative association could only be observed when nmol/L.

Markers such as β-HCG, CA125, ultrasound parameters, and progesterone are related to pregnancy outcome. However, some of them have their own disadvantages in assessing clinical condition. With serum β-HCG doubling approximately every 2 days and having individual differences [4], repeated measurements are needed to assess the embryo condition. CA125 is not a common measurement for threatened abortion patients, and studies about CA125 as a prediction of pregnancy outcomes are still controversial [23–25]. Additional CA125 detection may increase medical expenses. Ultrasound is commonly used to assess the condition of an embryo [26, 27]. However, parameters such as gestational sac diameter (GSD), yolk sac diameter (YSD), crown-rump length (CRL), and heart rate (HR) are difficult to obtain before the pregnancy sac is seen. Serum progesterone is a commonly used detection in threatened abortion women, its fluctuation is relatively small (compared with HCG), and the measurement is not limited by the gestational age. As far as we know, most studies suggested that serum progesterone levels were associated with pregnancy outcome, especially in the first trimester. Serum progesterone in abortion patients was generally lower than that in continuing pregnancy [10–14]. In our study, a negative correlation between serum progesterone and early pregnancy failure was further described. The risk of abortion decreased with the rise of serum progesterone.

In recent years, researches on the relationship between serum progesterone and pregnancy outcomes focused mainly on predictive models. Osmanağaoğlu et al. studied the predictive effects of progesterone, β-HCG, and CA125 for abortion. They found that using ng/mL (around 47.7 nmol/L) (, , , and ) or ng/mL (, , , and ) alone could better predict abortion than using them together (, , , and ) [24]. A study about the single measurement of serum progesterone was carried out; it showed that 32.7 ng/mL (around 103.99 nmol/L) (, , , and ) was the cut-off value of early pregnancy failure [20]. Al Mohamady et al. used progesterone and CA125 to predict pregnancy outcomes in patients with threatened miscarriage. The result showed both of them were valid predictions. The cut-off value of progesterone was 11.5 ng/mL (around 36.57 nmol/L) (, , ) [23]. Ku et al. used progesterone, fetal heart, and BMI to predict the outcome of spontaneous miscarriage. The ROC analysis showed a cut point of about 35 nmol/L progesterone (, , , and ) as the independent prediction [21]. Lek et al. had a verification experiment on this cut point; the result showed that 35 nmol/L was accurate and reproducible [22]. These studies showed that basal progesterone could be used as a prognostic marker of threatened abortion.

Although progesterone therapy is often used in patients with threatened abortion, the therapeutic effect is controversial. The European Progestin Club proposed that dydrogesterone can reduce the rate of spontaneous miscarriage in threatened abortion women [16]. A meta-analysis (combined with seven studies, a total of 696 participants) suggested that progesterone would decrease the miscarriage rate (RR 0.64, 95% CI 0.47 to 0.87) [17]. At the same time, another meta-analysis (combined with fourteen trials, a total of 2158 women) showed there was no statistically different abortion rate between women using progesterone therapy or not (Peto OR 0.99, 95% CI 0.78 to 1.24). In addition, the subgroup analysis (combined four trials, a total of 225 women) suggested that progesterone treatment might decrease the abortion rate of women with recurrent miscarriages (Peto OR 0.39, 95% CI 0.21 to 0.72) [19]. A multicenter, randomized, double-blind, placebo controlled trial in the United Kingdom indicated there was no significant increase in threatened abortion women’s live birth rate in the progesterone group compared to the placebo group (75% vs. 72%, RR 1.03, 95% CI 1.00 to 1.07, ) [18]. Based on our study, baseline serum progesterone had an impact on pregnancy outcomes within a certain range. Previous studies about progesterone treatment did not perform relevant analysis based on the patient’s progesterone level, which may affect the results of the studies.

All of the above evidence showed that serum progesterone was closely related to pregnancy outcomes, but the effectiveness of progesterone therapy is controversial. Our study found a saturation effect between serum progesterone and early pregnancy failure in threatened abortion patients. Only when nmol/L did abortion risk have negative association with serum progesterone. This prompted us to think that progesterone therapy may need more precise indications, especially in terms of serum progesterone values. A classic series study by Csapo et al. showed that patients who had ovariectomy or luteectomy at about 7 weeks of pregnancy would have progesterone decrease and abortion [28]. Luteectomized patients who had progesterone therapy sustained normal pregnancy [29]. Hensleigh and Fainstat conducted a study on corpus luteum dysfunction women with threatened or recurrent abortion. In 9/11 threatened abortion women who received progesterone therapy, serum progesterone was corrected and no abortion occurred [30]. Palagiano et al. conducted a prospective study on threatened abortion women with corpus luteum dysfunction. Compared to placebo, vaginal progesterone could reduce pain, uterine contractions, and abortion rate () [31]. These studies suggested that women with low serum progesterone could benefit from progesterone therapy. In China, threatened abortion patients with luteal dysfunction are recommended progesterone replacement [32]. However, the indications for progesterone therapy remain unclear. At present, there are no definitive values to diagnose progesterone deficiency [5]. Even considering luteal dysfunction as a replacement indication, the diagnosis of luteal dysfunction is controversial [33]. Therefore, large-scale, multicenter studies are needed to further evaluate the indication and effect of progesterone therapy.

Compared with previous studies, our research has the following progress. First of all, we found the inflection point of the saturation effect between baseline serum progesterone and first trimester abortion, which can better assist the clinician in understanding patients’ conditions and making medical decisions. Secondly, we proposed to further clarify indications for progesterone therapy in threatened abortion patients. Moreover, considering the effect of time and progesterone therapy on serum progesterone, we used a marginal structural model to demonstrate the reliability of our results.

5. Limitation

Our study had some limitations. Since our study was aimed at natural pregnancy patients with threatened abortion, the results of this study are only applicable to this population. Secondly, this study discussed the relationship between serum progesterone and the first trimester pregnancy outcome, and the results may not be applicable to delivery outcome. Thirdly, due to the limitation of the sample size, there was no subgroup analysis for different kinds of progesterone supplement.

6. Conclusions

In conclusion, our study showed a negative association and a saturation effect between baseline serum progesterone and the first trimester pregnancy outcome in threatened abortion women. This provided an idea that serum progesterone values may be considered as a reference for progesterone supplement. Further studies are needed to verify whether serum progesterone is a better indication for progesterone replacement.

Conflicts of Interest

The authors have no conflicts of interest.

Authors’ Contributions

YD participated in the design of study, the data collection and analysis, and the drafting and revising of the manuscript. CC performed statistical analysis and revised the manuscript. SC, GM, XL, HT, WL, YL, and SJ constructed the data together. SL and JG gave important guidance to the research design.

Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 81574011 and No. 81774358), the Traditional Chinese Medicine Heritage and Innovation “Hundreds, Thousands, and Ten Thousands” Talent Project (Qihuang Project)—the National Traditional Chinese Medicine Leading Talent Support Plan (Letter of Personnel Education Department of National Administration of Traditional Chinese Medicine [2018] No. 12), Pearl River Scholar Post Project in Guangdong Province (Letter of Teacher of Guangdong [2017] No. 79), and the First-Class Discipline Research Key Project of Guangzhou University of Chinese Medicine (High-Level University Construction) (No. A1-AFD018191A14).

Supplementary Materials

Both progesterone and β-HCG change over time. The supplementary material (Schedules 1-6) describes the trend of progesterone and β-HCG in different groups. In the schedule, the abscissa indicates the times of measurements and the ordinate indicates the mean and 95% CI of progesterone or β-HCG. Schedules 1-3 are about progesterone in nmol/L, while schedules 4-6 are about β-HCG in IU/L. Schedule 1 shows the trend of progesterone of threatened abortion patients. Schedule 2 shows the trend of progesterone of participants who continued pregnancy after 12 weeks of gestation. Schedule 3 shows the trend of progesterone of participants who miscarriage within 12 weeks. Schedule 4 shows the trend of β-HCG of threatened abortion patients. Schedule 5 shows the trend of β-HCG of participants who continued pregnancy after 12 weeks of gestation. Schedule 6 shows the trend of β-HCG of participants who miscarriage within 12 weeks. (Supplementary Materials)

References

F. Gary Cunningham, K. J. Leveno, S. L. Bloom, C. Y. Spong, and J. Dashe, Williams Obstetrics, McGraw-Hill Education, USA, 24th edition, 2014.
M. F. Greene, “Progesterone for threatened abortion,” New England Journal of Medicine, vol. 380, no. 19, pp. 1867-1868, 2019.
View at: Publisher Site | Google Scholar
J. Farren, N. Mitchell-Jones, J. Y. Verbakel, D. Timmerman, M. Jalmbrant, and T. Bourne, “The psychological impact of early pregnancy loss,” Human Reproduction Update, vol. 24, no. 6, pp. 731–749, 2018.
View at: Publisher Site | Google Scholar
B. L. Hoffman, J. O. Schorge, K. D. Bradshaw, L. M. Halvorson, and J. I. Schaffer, Williams Gynecology, McGraw-Hill Education, USA, 24th edition, 2016.
H. J. A. Carp, “Progestogens and pregnancy loss,” Climacteric, vol. 21, no. 4, pp. 380–384, 2018.
View at: Publisher Site | Google Scholar
A. Bogdan, G. Berta, and J. Szekeres-Bartho, “PIBF positive uterine NK cells in the mouse decidua,” Journal of Reproductive Immunology, vol. 119, pp. 38–43, 2017.
View at: Publisher Site | Google Scholar
M. L. Wolfson, J. A. Schander, M. V. Bariani, F. Correa, and A. M. Franchi, “Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism,” European Journal of Pharmacology, vol. 769, pp. 110–116, 2015.
View at: Publisher Site | Google Scholar
S. Arrowsmith, A. Kendrick, and S. Wray, “Drugs acting on the pregnant uterus,” Obstetrics, Gynaecology and Reproductive Medicine, vol. 20, no. 8, pp. 241–247, 2010.
View at: Publisher Site | Google Scholar
K. Czajkowski, J. Sienko, M. Mogilinski, M. Bros, R. Szczecina, and A. Czajkowska, “Uteroplacental circulation in early pregnancy complicated by threatened abortion supplemented with vaginal micronized progesterone or oral dydrogesterone,” Fertility and Sterility, vol. 87, no. 3, pp. 613–618, 2007.
View at: Publisher Site | Google Scholar
J. Y. S. Siew, J. C. Allen, C. Y. Y. Hui et al., “The randomised controlled trial of micronised progesterone and dydrogesterone (TRoMaD) for threatened miscarriage,” European Journal of Obstetrics, Gynecology, and Reproductive Biology, vol. 228, pp. 319–324, 2018.
View at: Publisher Site | Google Scholar
C. W. Ku, J. C. Allen Jr, S. M. Lek, M. L. Chia, N. S. Tan, and T. C. Tan, “Serum progesterone distribution in normal pregnancies compared to pregnancies complicated by threatened miscarriage from 5 to 13 weeks gestation: a prospective cohort study,” BMC Pregnancy and Childbirth, vol. 18, no. 1, pp. 360–365, 2018.
View at: Publisher Site | Google Scholar
C. A. Daily, S. L. Laurent, and W. C. Nunley Jr., “The prognostic value of serum progesterone and quantitative β-human chorionic gonadotropin in early human pregnancy,” American Journal of Obstetrics and Gynecology, vol. 171, no. 2, pp. 380–384, 1994.
View at: Publisher Site | Google Scholar
S. Rabiee, M. Hemmati, and N. Fallah, “Comparison of serum progesterone in non-viable pregnancy and ectopic pregnancy,” Acta Medica Iranica, vol. 51, no. 10, pp. 693–696, 2013.
View at: Google Scholar
P. C. Arck, M. Rücke, M. Rose et al., “Early risk factors for miscarriage: a prospective cohort study in pregnant women,” Reproductive Biomedicine Online, vol. 17, no. 1, pp. 101–113, 2008.
View at: Publisher Site | Google Scholar
Y. Sun, P. Liu, H. Ye, Q. F. Wu, X. Y. Liu, and H. X. Yang, “Luteal support and progesterone supplementation consensus,” Reproduction & Contraception, vol. 35, no. 1, pp. 1–8, 2015.
View at: Google Scholar
A. E. Schindler, H. Carp, R. Druckmann et al., “European Progestin Club guidelines for prevention and treatment of threatened or recurrent (habitual) miscarriage with progestogens,” Gynecological Endocrinology, vol. 31, no. 6, pp. 447–449, 2015.
View at: Publisher Site | Google Scholar
H. A. Wahabi, A. A. Fayed, S. A. Esmaeil, and K. H. Bahkali, “Progestogen for treating threatened miscarriage,” Cochrane Database of Systematic Reviews, vol. 8, 2018.
View at: Google Scholar
A. Coomarasamy, A. J. Devall, V. Cheed et al., “A randomized trial of progesterone in women with bleeding in early pregnancy,” The New England Journal of Medicine, vol. 380, no. 19, pp. 1815–1824, 2019.
View at: Publisher Site | Google Scholar
D. M. Haas and P. S. Ramsey, “Progestogen for preventing miscarriage,” Cochrane Database Syst Rev, vol. 10, 2013.
View at: Google Scholar
O. Hanita and A. H. Hanisah, “Potential use of single measurement of serum progesterone in detecting early pregnancy failure,” The Malaysian Journal of Pathology, vol. 34, no. 1, pp. 41–46, 2012.
View at: Google Scholar
C. W. Ku, J. C. Allen Jr., R. Malhotra et al., “How can we better predict the risk of spontaneous miscarriage among women experiencing threatened miscarriage?” Gynecological Endocrinology, vol. 31, no. 8, pp. 647–651, 2015.
View at: Publisher Site | Google Scholar
S. M. Lek, C. W. Ku, J. C. Allen Jr et al., “Validation of serum progesterone <35nmol/L as a predictor of miscarriage among women with threatened miscarriage,” BMC Pregnancy and Childbirth, vol. 17, no. 1, pp. 78–84, 2017.
View at: Publisher Site | Google Scholar
M. Al Mohamady, G. A. Fattah, E. Elkattan, R. Bayoumy, and D. A. Hamed, “Correlation of serum CA-125 and progesterone levels with ultrasound markers in the prediction of pregnancy outcome in threatened miscarriage,” International Journal of Fertility & Sterility, vol. 9, no. 4, pp. 506–511, 2016.
View at: Publisher Site | Google Scholar
M. A. Osmanağaoğlu, I. Erdoğan, S. Eminağaoğlu et al., “The diagnostic value of beta-human chorionic gonadotropin, progesterone, CA125 in the prediction of abortions,” Journal of Obstetrics and Gynaecology, vol. 30, no. 3, pp. 288–293, 2010.
View at: Publisher Site | Google Scholar
L. S. Sherif, A. G. El-Metwaly, and H. Sha, “Can a single serum CA125 assay predict the outcome of threatened abortion?” Journal of Obstetrics and Gynaecology, vol. 20, no. 1, pp. 65–67, 2000.
View at: Publisher Site | Google Scholar
G. I. Papaioannou, A. Syngelaki, N. Maiz, J. A. Ross, and K. H. Nicolaides, “Ultrasonographic prediction of early miscarriage,” Human Reproduction, vol. 26, no. 7, pp. 1685–1692, 2011.
View at: Publisher Site | Google Scholar
M. R. Datta and A. Raut, “Efficacy of first-trimester ultrasound parameters for prediction of early spontaneous abortion,” International Journal of Gynaecology and Obstetrics, vol. 138, no. 3, pp. 325–330, 2017.
View at: Publisher Site | Google Scholar
A. I. Csapo, M. O. Pulkkinen, B. Ruttner, J. P. Sauvage, and W. G. Wiest, “The significance of the human corpus luteum in pregnancy maintenance. I. Preliminary studies,” American Journal of Obstetrics and Gynecology, vol. 112, no. 8, pp. 1061–1067, 1972.
View at: Publisher Site | Google Scholar
A. I. Csapo, M. O. Pulkkinen, and W. G. Wiest, “Effects of luteectomy and progesterone replacement therapy in early pregnant patients,” American Journal of Obstetrics and Gynecology, vol. 115, no. 6, pp. 759–765, 1973.
View at: Publisher Site | Google Scholar
P. A. Hensleigh and T. Fainstat, “Corpus luteum dysfunction: serum progesterone levels in diagnosis and assessment of therapy for recurrent and threatened abortion,” Fertility and Sterility, vol. 32, no. 4, pp. 396–400, 1979.
View at: Publisher Site | Google Scholar
A. Palagiano, C. Bulletti, M. C. Pace, D. D. E. Ziegler, E. Cicinelli, and A. Izzo, “Effects of vaginal progesterone on pain and uterine contractility in patients with threatened abortion before twelve weeks of pregnancy,” Annals of the New York Academy of Sciences, vol. 1034, no. 1, pp. 200–210, 2004.
View at: Publisher Site | Google Scholar
X. Xie, B. Kong, T. Duan et al., Obstetrics and Gynecology, People’s Medical Publishing House, China, 9th edition, 2018.
A. Czyzyk, A. Podfigurna, A. R. Genazzani, and B. Meczekalski, “The role of progesterone therapy in early pregnancy: from physiological role to therapeutic utility,” Gynecological Endocrinology, vol. 33, no. 6, pp. 421–424, 2017.
View at: Publisher Site | Google Scholar

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Copyright © 2020 Yongshi Deng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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