Comparison Between Oral Dydrogesterone versus Intravaginal Micronized Progesterone Gel in Clinical Outcome within the First HRT-FET Cycle: A Retrospective Analysis

doi:10.21203/rs.3.rs-3799394/v1

Objective

The purpose of this study is to compare the clinical efficacy of oral dydrogesterone and intravaginal micronized progesterone gel during the first HRT-FET cycle.

Methods

A retrospective cohort study based on a total of 344 women undergoing their first HRT-FET cycles without Gonadotropin-Releasing Hormone agonist (GnRH-a) pretreatment was conducted. All the cycles were allocated to two groups in the reproductive medical center at the University of Hong Kong-Shenzhen Hospital. One group (n = 193) received oral dydrogesterone 30mg/d before embryo transfer, while the other group (n = 151) received intravaginal micronized progesterone gel 180mg/d.

Results

The demographics and baseline characteristics of two groups were comparable. We found no statistically significant difference in live birth rate (24.35% vs. 31.13%, P = 0.16), clinical pregnancy rate (34.72% vs. 36.42%, P = 0.74), embryo implantation rate (25.09% vs. 28.36%, P = 0.43), positive pregnancy rate (42.49% vs 38.41%, P = 0.45), or ectopic pregnancy rate (0.52% vs. 0.66%, P = 0.86) between the oral dydrogesterone group and micronized vaginal progesterone (MVP) gel group. In the multivariate logistic regression analysis for covariates, medication used for luteal support was not associated with live birth rate (OR = 0.74, 95% CI: 0.46–1.21, P = 0.23). And the different luteal support medication did not have a significant positive association with the live birth rate in the cycles with day 2 embryo transferred (OR = 0.73, 95% CI:0.34–1.54, P = 0.41) and blastocyst transferred (OR = 0.75, 95% CI:0.36–1.57, P = 0.45).

Conclusion

This study demonstrates that oral dydrogesterone is a viable alternative to intravaginal micronized progesterone gel in luteal phase support (LPS) during the first HRT-FET cycle.

Dydrogesterone

Micronized progesterone gel

Hormone Replacement Treatment (HRT)

Frozen-thawed Embryo Transfer (FET)

luteal phase support (LPS)

Since 1983, frozen-thawed embryo transfers (FET) have been widely performed around the world [1]. After years of development embryo freezing technology has become very mature leading to a higher accumulated pregnancy rate. Compared to fresh embryo transfer, FET cycle avoids the risk for ovarian hyperstimulation syndrome [2]. Also, FET is an essential protocol in cases where the embryo needs to undergo preimplantation genetic diagnosis and screening. FET protocol includes artificial FET (a-FET), natural cycle based on spontaneous ovulation, or modified natural cycle using ovulation induction. A-FET protocol is also called Hormone Replacement Treatment Frozen-Thawed Embryo Transfers (HRT-FET) because exogenous estrogen and progesterone were used in endometrial preparation and luteal phase support (LPS) [3]. This protocol which originally developed from the embryo transfer cycle with donated oocytes has been proved applicable for the general women population. Additionally, easy monitoring and scheduling were its most obvious advantages [4].

Defective secretory transformation of the endometrium or luteal phase deficiency, is still a challenging concept in reproductive endocrinology [5]. In the HRT-FET cycle, no endogenous progesterone is produced due to a lack of functional corpus luteum. Following endometrial preparation, exogenous progesterone is required for embryo implantation and pregnancy maintenance in this protocol. Exogenous progesterone can be administered in different formulations, including oral, intramuscular, vaginal, or rectal preparations. Vaginal progesterone has the clinical advantage of rapid absorption, endometrial concentration, and local effect. But vaginal medication could induce some side effects including vaginal irritation, increased discharge, and bleeding [6]. As to Intramuscular administration, we sometimes received complaints about pain and local swelling at the injection site from patients. Oral progesterone is more convenient but is associated with low bioavailability resulting from a substantial first-pass metabolism, and causes somnolence or a headache as side effects [7].

Dydrogesterone, an optical isomer of progesterone, is available in an oral form with high oral bioavailability. It has been used to treat a variety of conditions related to progesterone deficiency since the 1960s and has recently been approved for LPS as part of an assisted reproductive technology treatment [8]. Dydrogesteron is a selective progesterone receptor agonist, but with better oral bioavailability compared with oral micronized progesterone [8]. Further, an international Phase III randomized controlled trial (Lotus I), demonstrated that oral dydrogesterone was not inferior to micronized vaginal progesterone (MVP) in terms of pregnancy rates at 12 weeks of gestation or the live birth rates of fresh embryo transfer protocol. It was well tolerated and had a similar safety profile to MVP [9]. The Lotus II study involving 980 ART cycles, which compared oral dydrogesterone with intravaginal micronized progesterone gel, resulted in a similar conclusion [10]. Compared to MVP gel, oral dydrogesterone is more convenient and significantly reduces patients’ medical costs. Although several studies reported on the effectiveness and safety of oral dydrogesterone in HRT-FET, only a few of them compared dydrogesterone alone vs intravaginal progesterone alone in the process of endometrium preparation prior to transplantation and LPS. The present study aimed to compare oral dydrogesterone with intravaginal micronized progesterone gel in the HRT-FET treatment, using the routine clinical parameters and pregnancy outcomes.

Study design

A retrospective observational study was performed at the Center of Reproductive Medicine, the University of Hong Kong-Shenzhen Hospital using data from 2015 to 2020.

FET protocol and LPS

Each cycle was the first HRT-FET cycle of the patient. All the HRT-FET cycles without the downregulation of Gonadotropin-Releasing Hormone agonist (GnRH-a) were included in the analysis. The endometrium was prepared with the administration of estrogen and progesterone.

Blood was collected to determine serum estradiol (E2) and progesterone (P4) concentrations. Estradiol valerate at 2 mg three times daily was started on day 2 of the menstrual cycle for 14 days, E2 concentration was ≤ 60 pg/mL, and P4 concentration was ≤ 1.6 ng/mL on day 2. A transvaginal ultrasound examination was performed to measure the endometrial thickness and a blood test was conducted to determine serum E2 and P4 concentrations after the use of estradiol valerate for 14 days. If the endometrium thickness was ≥ 7 mm and serum P4 concentration was ≤ 1.6 ng/mL, the women continued with oral estradiol valerate at 6 mg daily and oral dydrogesterone (Duphaston 10 mg tablet, Abbott Healthcare Products, Netherlands) at 10 mg three times daily or intravaginal micronized progesterone gel (Crinone 8% 90mg, Serono, Switzerland) two times daily. The dose of estradiol valerate was increased to 8 mg daily for a week if the endometrial thickness was < 7 mm. Then, the transvaginal ultrasound examination was repeated to determine the endometrial thickness. The cycle was canceled if the endometrial thickness remained < 7 mm. For the embryos stored on day 2 after the oocyte’s retrieval, the transfer was done on the 4th day of starting progesterone while for the blastocysts stored on day 5 or 6, the transfer was performed on the 7th day of starting progesterone. A blood pregnancy test was carried out 18 days after starting progesterone. If the pregnancy test was positive, the women continued oral estradiol valerate and progesterone daily up to 12 weeks of gestation.

Outcome measures

The primary outcome was live birth rate per embryo transfer. The secondary outcomes included positive pregnancy rate, clinical pregnancy rate, ectopic pregnancy rate, embryo implantation rate, miscarriages and neonatal weight. Positive pregnancy test was defined if the serum human chorionic gonadotropin, beta subunit (beta-hCG) concentration > 5.83 IU/L and the clinical pregnancy was confirmed by ultrasound examination 4–5 weeks after embryo transfer. Miscarriage was defined if the clinical pregnancy was lost spontaneously before 20 weeks of gestation. Implantation rate was defined as the ratios of the gestational sac number over the transferred embryo number.

Statistical analysis

Shapiro-Wilk test was performed to examine the normality of continuous variables, indicating the variables were normally distributed. Thus, all the variables were expressed as a mean ± SD and analyzed with the student’s t-test. Additionally, categorical variables were expressed as percentages (frequency) and studied utilizing the Pearson Chi-square test or Fisher’s exact probability. A multivariate logistic regression model was used to reduce bias caused by some potential confounding factors and to identify associations between live birth rate and different progesterone administration. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated. All statistical analyses were run by software SPSS (version 23, IBM, USA), with P < 0.05 (two-tailed) regarded as a significant difference.

A total of 344 HRT-FET cycles were analyzed in the study. Oral dydrogesterone was administered in 193 cycles whereas intravaginal micronized progesterone gel was applied in 151 cycles. Table 1 presents the baseline parameters. The cycles characteristics, including age, body mass index (BMI), antral follicle count (AFC), number of embryos transferred, serum estradiol and progesterone levels on day 2 of the menstrual cycle and the endometrial thickness on the day 2 of the menstrual cycle and the day before endometrial transformation, in each group were comparable.

Table 2 shows the clinical outcomes after the embryo transfer. No significant difference was found in the clinical pregnancy rate (34.72% vs. 36.42%, P=0.74), live birth rate (24.35% vs. 31.13%, P=0.16), embryo implantation rate (25.09% vs. 28.36%, P=0.43), positive pregnancy rate (42.49% vs 38.41%, P=0.45), miscarriage rate (22.78% vs 10.71%, P=0.07), and ectopic pregnancy rate (0.52% vs. 0.66%, P=0.86) between the oral dydrogesterone group and the intravaginal micronized progesterone gel group.

Table 3 presents the different clinical outcomes between the day 2 cleavage stage embryo and blastocyst transfer. In the day 2 cleavage stage embryo transfer subgroup, there was no statistical difference in live birth rate (17.60% vs. 21.69%, P=0.46), clinical pregnancy rate (25.60% vs. 24.10%, P=0.81), embryo implantation rate (16.08% vs. 15.87%, P=0.96), positive pregnancy test (33.60% vs. 27.71%, P=0.37), and ectopic pregnancy rate (0.8% vs. 0%, P=0.41) between the oral dydrogesterone group and the intravaginal micronized progesterone gel group. Additionally, there was no statistically significant difference in the average number of embryos transferred between the two groups (P=0.30). In the blastocyst transfer subgroup, there was no significant difference in live birth rate (17.60% vs. 21.69%, P=0.46), clinical pregnancy rate (53.97% vs. 51.47%, P=0.77), embryo implantation rate (53.97% vs. 51.47%, P=0.77), positive pregnancy test rate (60.32% vs. 51.47%, P=0.31), and ectopic pregnancy rate (0.00% vs. 1.47%, P=0.33). Single blastocyst transfer strategy was performed. Therefore, there was no statistically significant difference in the average number of embryos transferred between the two groups.

A multivariate logistic regression analysis (Table 4) was performed in which live birth rate was the dependent variable and the covariates were woman’s age, BMI, medication used for luteal support, AFC, serum estradiol and progesterone level on day 2 of menstrual cycle, and on the day before endometrial transformation, endometrial thickness on day 2 of the menstrual cycle and the day before endometrial transformation. Table 4 shows that different luteal support medication did not have a significant positive association with the live birth rate (OR = 0.74, 95% CI:0.46-1.21, P=0.23). Table 5 and table 6 shows the different luteal support medication did not have a significant positive association with the live birth rate in the cycles with day 2 embryo transferred (OR = 0.73, 95% CI:0.34-1.54, P=0.41) and blastocyst transferred (OR = 0.75, 95% CI:0.36-1.57, P=0.45).

Table 1 Baseline characteristics (full analysis sample)
Demographics	Oral DYD (n=193)	MVP gel (n=151)	P-value
Mean age, years (SD)	33.09±4.24	32.44±3.52	0.15
Age category, n (%)
≤35 years of age	140 (72.54)	121 (80.13)
>35 years of age	53 (27.46)	30 (19.87)
Mean BMI (Kg/m2) (SD)	21.94±3.96	21.89±2.89	0.88
Infertility, n (%)
Primary	121 (62.69)	103 (68.21)
Secondary	72 (37.31)	48 (31.79)
Cause of infertility, n (%)
Tubal factor Aovulated factor Endometriosis Male factor Coital factor Unexplained	79(40.93) 51(26.42) 15(7.77) 35 (18.13) 4(2.07) 9 (4.66)	66(43.71) 36(23.84) 12(7.95) 31 (20.53) 0(0) 6 (3.97)
AFC (SD)	16.23±10.95	17.05±10.14	0.48
Number of embryos transferred (SD)	1.38±0.49	1.28±0.45	0.05
Estradiol level on day 2 of the menstrual cycle (pg/ml) (SD)	46.54±15.85	47.87±19.39	0.49
Estradiol level before the endometrial transformation day (pg/ml) (SD)	283.31±138.73	268.34±145.74	0.34
Progesterone level on day 2 of menstrual cycle (pg/ml) (SD)	0.64±0.30	0.99±4.51	0.35
Progesterone level before endometrial transformation day (pg/ml) (SD)	0.54±0.38	0.52±0.30	0.54
Endometrial thickness on day 2 of menstrual cycle (mm) (SD)	5.37±0.87	5.35±1.16	0.87
Endometrial thickness before the endometrial transformation day (mm) (SD) Ratio of Day 2 embryo/blastosyct	9.23±1.48 64.77%	9.22±1.39 54.97%	0.93 0.07
AFC, antral follicle count; BMI, body mass index; DYD, dydrogesterone; MVP, micronized vaginal progesterone; SD, standard deviation

Table 2 Pregnancy outcomes for FET cycles %(n/N)
Outcome	%(n/N)		P-value
Outcome	Oral DYD	MVP gel	P-value
Live birth	24.35 (47/193)	31.13 (47/151)	0.16
Clinical pregnancy	34.72 (67/193)	36.42 (55/151)	0.74
Embryo implantation	25.09 (67/267)	28.36 (55/194)	0.43
Positive pregnancy test	42.49 (82/193)	38.41 (58/151)	0.45
Ectopic pregnancy	0.52 (1/193)	0.66 (1/151)	0.86
DYD, dydrogesterone; MVP, micronized vaginal progesterone; SD, standard deviation

Table 3 Pregnancy outcomes for day 2 cleavage embryo and blastosyct of FET cycles %(n/N)
Outcome	Day2 cleavage embryo		P-value	Blastocyst		P-value
Outcome	Oral DYD	MVP gel	P-value	Oral DYD	MVP gel	P-value
Live birth	17.60 (22/125)	21.69 (18/83)	0.46	36.76 (25/68)	42.65 (29/68)	0.73
Clinical pregnancy	25.60 (32/125)	24.10 (20/83)	0.81	50.00 (34/68)	51.47 (35/68)	0.86
Embryo implantation	16.08 (32/199)	15.87 (20/126)	0.96	50.00 (34/68)	51.47 (35/68)	0.86
Positive pregnancy test	33.60 (42/125)	27.71 (23/83)	0.37	52.94 (38/68)	51.47 (35/68)	0.61
Ectopic pregnancy	0.8 (1/125)	0.00 (0/83)	0.41	0.00 (0/68)	1.47 (1/68)	0.33
Number of embryos transferred (SD)	1.59±0.49	1.52±0.50	0.30	1	1
DYD, dydrogesterone; MVP, micronized vaginal progesterone; SD, standard deviation

Table 4 Multivariate logistic regression analysis for factors affecting the live birth
Variable	Odds ratio	95% CI	P-Value
Age	1.067	0.99-1.14	0.05
BMI	1.00	0.91-1.07	1.00
Medication used for luteal support	0.74	0.46-1.21	0.23
AFC	1.01	0.98-1.03	0.61
Estradiol level on day 2 of menstrual cycle	0.99	0.98-1.01	0.42
Estradiol level before the endometrial transformation day	1.00	0.99-1.00	0.31
Progesterone level on day 2 of menstrual cycle	1.09	0.75-1.58	0.66
Progesterone level before the endometrial transformation day	2.00	0.84-4.81	0.12
Endometrial thickness on day 2 of menstrual cycle	1.01	0.80-1.28	0.94
Endometrial thickness before the endometrial transformation day	0.85	0.72-1.00	0.56
AFC, antral follicle count; BMI, body mass index; CI: confidence interval

Table 5 Multivariate logistic regression analysis for factors affecting the live birth from the day 2 cleavage embryo transferred cycles.
Variable	OR	95%CI	P-Value
Age	0.94	0.85-1.04	0.24
BMI	1.02	0.93-1.12	0.71
Luteal support medication.	0.73	0.34-1.54	0.41
Antral follicle count	0.94	0.89-0.99	0.02
A total number of eggs	1.03	0.97-1.09	0.38
Oestradiol level on days 2 of menstruation	1.00	0.97-1.02	0.72
Oestradiol level before endometrial transformation day	1.00	0.99-1.00	0.23
Progesterone level on days 2-4 of menstruation	1.22	0.38-3.89	0.74
Progesterone level before endometrial transformation day	0.13	0.03-0.69	0.02
Endometrial thickness on days 2 of menstruation	0.96	0.67-1.35	0.11
Endometrial thickness before endometrial transformation day	0.95	0.67-1.35	0.78

Table 6 Multivariate logistic regression analysis for factors affecting the live birth from the blastocyst transferred cycles.
Variable	OR	95%CI	P-Value
Age	0.92	0.84-1.02	0.12
BMI	1.03	0.90-1.17	0.69
Luteal support medication.	0.75	0.36-1.57	0.45
Antral follicle count	1.01	0.97-1.05	0.81
A total number of eggs	1.00	0.95-1.04	0.77
Oestradiol level on days 2 of menstruation	1.02	0.99-1.04	0.11
Oestradiol level before endometrial transformation day	1.00	0.99-1.00	0.96
Progesterone level on days 2 of menstruation	0.74	0.20-2.71	0.65
Progesterone level before endometrial transformation day	1.07	0.33-3.44	0.91
Endometrial thickness on days 2 of menstruation	1.25	0.94-1.65	0.13
Endometrial thickness before endometrial transformation day	1.09	0.74-1.60	0.66

Dydrogesterone has been used widely as a luteal supplement because of its effectiveness and safety shown in Fresh ET [9, 10]. Also, several research studies have proved that it is applicable in HRT [11, 12]. A random controlled trial showed that oral dydrogesterone provided similar ongoing pregnancy rates with fewer intolerable side effects compared to MVP gel as a LPS in modified natural cycle FET (mNC-FET) [3]. In mNC-FET, ovulation induction increases endogenous sex hormones, which benefits embryo implantation and pregnancy maintenance. Currently, there is still controversy over whether luteal support is needed for mNC-FET. In our study, all the cycles were HRT-FET protocol and avoided interference from endogenous progestogen. A pilot randomized controlled trial compared the clinical efficacy of oral dydrogesterone with both vaginal progesterone suppository and intramuscularly injected progesterone for LPS in artificial FET cycles and concluded that dydrogesterone could be prescribed for LPS in artificial FET cycles as effective as either intramuscular or vaginal supplements. It seems to be more accepted by patients in terms of ease of use and lower cost [5]. Another pilot randomized controlled trial reported that treatment with 40 mg/d oral dydrogesterone, 180 mg/d progesterone vaginal gel or 100 mg/d intramuscular administration evealed similar reproductive outcomes in HRT-FET cycles [13]. In the above two studies, the daily dosage of dydrogesterone reached 40mg which exceeds the recommended dosage (30mg per day) of the drug prescribed for Chinese women and so was rarely applied in our center. Atzmon et al. retrospectively analysis the different LPS protocols in FET cycles, the dydrogesterone’s dosage of 30 mg per day was chosen in the HRT-FET cycles. However, its FET protocol included HRT-FET, natural cycle FET and modified natural cycle FET, and the clinical outcomes was analyzed from all the FET protocols not from the HRT-FET protocol only. Therefore single use of 30 mg dydrogesterone per day just in HRT-FET cycles was a novel clinical practice so far.

In addition, various studies on LPS of HRT-FET adopted more than one progesterone administration to increase the progesterone concentration in the serum or locally in the uterine tissues [14, 15]. The main reason is a lack of functional natural corpus luteum in the HRT cycle. So exogenous administration is essential for promoting pregnancy. In the clinical practice, various kinds of progesterone were performed, even combined use of two administrations were tried [12, 16]. However, excessive intake of progestogen may induce higher risk of drug side effects and increase medical expenses. The dosage of 30 mg per day was reported in the clinical trial of Lotus I and Lotus II, and the clinical outcome was accepted and reasonable. Therefore, in our study, all the patients only took one progesterone medication and the dosage of dydrogesterone was 30 mg per day.

In the past two decades, several studies have reported on pituitary downregulation before frozen embryo transfer. Some demonstrated that pituitary downregulation improved clinical outcomes [17, 18]. In contrast other studies showed that this treatment had no significant effect in FET [19, 20]. In our clinical observation, we found using GnRH-a or gonadotropin-releasing hormone antagonists (GnRH-A) before HRT-FET did not increase pregnancy rate. For these two reasons, we did not provide pretreatment with a GnRH-a or GnRH-A. In the study, a few cases of spontaneous ovulation with the 6 mg dosage of E2 were observed and then canceled.

In this study, there was no significant difference in the primary outcome live birth rate between the two groups. This result showed that the use of oral dydrogesterone alone could be sufficient for the embryo implantation and LPS. We did not perform the propensity score matching because the baseline parameters of the two groups were comparable. Furthermore, the multivariate logistic regression analysis adjusted for the covariates, and they were not associated with live birth rate, the same results were shown from the day 2 cleavage embryo or blastocyst subgroups. The other parameters did not show any significant difference between the two groups, even when we subgrouped them with day 2 cleavage embryo or blastocyst.

The limitation of this study is its retrospective nature despite its strengths. It may need more cycle numbers to increase the sample size. The prospective RCT can be designed in the future to substantiate the evidence of oral dydrogesterone effectiveness and safety in the HRT-FET treatment.

In conclusion, 30 mg/d oral dydrogesterone and 180 mg/d intravaginal micronized progesterone gel revealed similar reproductive outcomes in HRT-FET cycles in the study.

Funding:

This study did not receive any specific grant from any funding agency.

Competing interests:

The authors have no conflicts of interest to disclose.

Authors' contributions:

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Tian-Min Ye, Long-Dan Luo, Yuan-Fei Huang and Shufang Ding. The first draft of the manuscript was written by Tian-Min Ye and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Ethical approval:

The study was approved by the ethical committee of the University of Hong Kong-Shenzhen Hospital and the approval number was 2022-170.

Consent to participate:

Informed consent was obtained from all individual participants included in the study.

Consent for publication:

All the patients signed the consent form before IVF treatment.

Availability of data and materials:

The data that support the findings of this study are available from the corresponding author upon reasonable request and with permission of the corresponding author.

Acknowledgements:

Nil

Financial interests: All Authors declare they have no financial interests.

Non-financial interests: none.

Trounson A, Mohr L. (1983) Human pregnancy following cryopreservation, thawing and transfer of an eight-cell embryo. 305(5936):707-9.
Prevention and treatment of moderate and severe ovarian hyperstimulation syndrome: a guideline. (2016) Fertil Steril 106(7):1634-47.
Ozer G, Yuksel B, Yucel Cicek OS, Kahraman S. (2021) Oral dydrogesterone vs. micronized vaginal progesterone gel for luteal phase support in frozen-thawed single blastocyst transfer in good prognosis patients. J Gynecol Obstet Hum Reprod May;50(5):102030.
Younis JS, Simon A, Laufer N. (1996) Endometrial preparation: lessons from oocyte donation. Fertil Steril 66(6):873-84.
Rashidi BH, Ghazizadeh M, Tehrani Nejad ES, Bagheri M, Gorginzadeh M. (2016) Oral dydrogesterone for luteal support in frozen-thawed embryo transfer artificial cycles: A pilot randomized controlled trial. Asian Pacific Journal of Reproduction 5(6):490-4.
Ghanem ME, Bakre NI, Emam MA, Al Boghdady LA, Helal AS, Elmetwally AG, et al. (2011) The effects of timing of intrauterine insemination in relation to ovulation and the number of inseminations on cycle pregnancy rate in common infertility etiologies. Hum Reprod Mar;26(3):576-83.
Shapiro D, Boostanfar R, Silverberg K, Yanushpolsky EH. (2014) Examining the evidence: progesterone supplementation during fresh and frozen embryo transfer. Reprod Biomed Online. Suppl 1:S1-14; quiz S5-6.
Griesinger G, Tournaye H, Macklon N, Petraglia F, Arck P, Blockeel C, et al. (2019) Dydrogesterone: pharmacological profile and mechanism of action as luteal phase support in assisted reproduction. Reprod Biomed Online 38(2):249-59.
Tournaye H, Sukhikh GT, Kahler E, Griesinger G. (2017) A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization. Hum Reprod 32(10):2152.
Griesinger G, Blockeel C, Sukhikh GT, Patki A, Dhorepatil B, Yang DZ, et al. (2018) Oral dydrogesterone versus intravaginal micronized progesterone gel for luteal phase support in IVF: a randomized clinical trial. Hum Reprod 33(12):2212-21.
Zarei A, Sohail P, Parsanezhad ME, Alborzi S, Samsami A, Azizi M. (2017) Comparison of four protocols for luteal phase support in frozen-thawed Embryo transfer cycles: a randomized clinical trial. Arch Gynecol Obstet 295(1):239-46.
Atzmon Y, Aslih N, Estrada D, Bilgory A, Ellenbogen A, Shalom-Paz E. (2021) Comparable Outcomes Using Oral Dydrogesterone Vs. Micronized Vaginal Progesterone in Frozen Embryo Transfer: a Retrospective Cohort Study. Reprod Sci 28(7):1874-81.
Pabuccu E, Kovanci E, Israfilova G, Tulek F, Demirel C, Pabuccu R. Oral, (2022) vaginal or intramuscular progesterone in programmed frozen embryo transfer cycles: a pilot randomized controlled trial. Reprod Biomed Online 45(6):1145-51.
Alsbjerg B, Thomsen L, Elbaek HO, Laursen R, Povlsen BB, Haahr T, et al. (2020) Can combining vaginal and rectal progesterone achieve the optimum progesterone range required for implantation in the HRT-FET model? Reprod Biomed Online 40(6):805-11.
Xu H, Zhang XQ, Zhu XL, Weng HN, Xu LQ, Huang L, et al. (2021) Comparison of vaginal progesterone gel combined with oral dydrogesterone versus intramuscular progesterone for luteal support in hormone replacement therapy-frozen embryo transfer cycle. J Gynecol Obstet Hum Reprod 50(7):102110.
Mackens S, Santos-Ribeiro S, van de Vijver A, Racca A, Van Landuyt L, Tournaye H, et al. (2017) Frozen embryo transfer: a review on the optimal endometrial preparation and timing. Hum Reprod 32(11):2234-42.
Hill MJ, Miller KA, Frattarelli JL. (2010) A GnRH agonist and exogenous hormone stimulation protocol has a higher live-birth rate than a natural endogenous hormone protocol for frozen-thawed blastocyst-stage embryo transfer cycles: an analysis of 1391 cycles. Fertil Steril 93(2):416-22.
Hebisha SA, Adel HM. (2017) GnRh Agonist Treatment Improves Implantation and Pregnancy Rates of Frozen-Thawed Embryos Transfer. J Obstet Gynaecol India 67(2):133-6.
Gelbaya TA, Nardo LG, Hunter HR, Fitzgerald CT, Horne G, Pease EE, et al. (2006) Cryopreserved-thawed embryo transfer in natural or down-regulated hormonally controlled cycles: a retrospective study. Fertil Steril 85(3):603-9.
Kang J, Park J, Chung D, Lee SH, Park EY, Han KH, et al. (2018) Comparison of the clinical outcome of frozen-thawed embryo transfer with and without pretreatment with a gonadotropin-releasing hormone agonist. Obstet Gynecol Sci 61(4):489-96.

Comparison Between Oral Dydrogesterone versus Intravaginal Micronized Progesterone Gel in Clinical Outcome within the First HRT-FET Cycle: A Retrospective Analysis

Status:

Journal Publication

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Abstract

Objective

Methods

Results

Conclusion

Introduction

Methods

Study design

FET protocol and LPS

Outcome measures

Statistical analysis

Results

Discussion

Declarations

References

Status:

Journal Publication

Version 1