International Journal of Reproduction, Contraception, Obstetrics and Gynecology

Patki A et al. Int J Reprod Contracept Obstet Gynecol. 2024 Nov;13(11):3432-3439

[Link] pISSN 2320-1770 | eISSN 2320-1789

DOI: [Link]
Review Article

Recent trends on dydrogesterone in gynaecology, obstetrics, and

infertility: insights from Indian experts
Ameet Patki1, Rajul Tyagi2, Geeta Khanna3, Sweta Agarwal4, Rajan Vaidya5, Sachin Dalal6,
Parikshit Tank7, Asha Baxi8, Vijay Pawar9, Rita Bakshi10, Abhijeet Kumar11,
Prashant Katke11*, Sachin Suryawanshi11

1
Fertility Associates, Mumbai, Maharashtra, India
2
Javitri Hospital, Lucknow, Uttar Pradesh, India
3
Ajanta IVF Centre, Lucknow, Uttar Pradesh, India
4
Department of Fertility and Gynaecology, Southern Gem Hospital, Hyderabad, India
5
Victoria International IVF Centre, Mumbai, Maharashtra, India
6
Madhu Hospital, Bhandup, Mumbai, Maharashtra, India
7
Ashwini Maternity and Surgical Hospital, Mumbai, Maharashtra, India
8
Motherhood Women and Children Hospital, Mumbai, Maharashtra, India
9
Department of Obstetrics and Gynaecology, Sims Fertility Centre, Solapur, Maharashtra, India
10
RISAA IVF, Delhi, India
11
Medical Services, Emcure Pharmaceuticals, Mumbai, Maharashtra, India

Received: 29 August 2024

Accepted: 04 October 2024

*Correspondence:
Dr. Prashant Katke,
E-mail: [Link]@[Link]

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Infertility affects millions globally, with significant prevalence in India due to conditions like endometriosis and
polycystic ovarian syndrome (PCOS). Dydrogesterone, a synthetic progesterone, has demonstrated efficacy in managing
endometriosis, recurrent pregnancy loss (RPL), and infertility. Endometriosis, affecting 10% of reproductive-aged
women, often leads to infertility and recurrent pain despite surgical interventions. Dydrogesterone 20 mg effectively
reduces chronic pelvic pain and improves quality of life in these patients. In infertility management, dydrogesterone
enhances luteal phase support (LPS), leading to higher pregnancy rates and better reproductive outcomes compared to
other progesterone forms. It is particularly beneficial in in vitro fertilization (IVF) and intrauterine insemination (IUI)
cycles, showing improved patient compliance and reduced side effects. For RPL, dydrogesterone stabilizes the
endometrial environment, supporting implantation and early embryonic development. Its use in PCOS aids in menstrual
regulation and pregnancy preparation without inhibiting ovulation. Expert opinions from Indian gynaecologists
highlight the need for tailored dydrogesterone protocols to address the unique challenges in Indian healthcare. This
document gathers insights from these experts, emphasizing the therapeutic potential of dydrogesterone in gynaecology,
obstetrics, and infertility management.

Keywords: Dydrogesterone, Infertility, Endometriosis, RPL, PCOS, Gynaecology and obstetrics

INTRODUCTION (WHO), one in every four couples in developing countries

is affected by infertility. In India alone, approximately 15-
Infertility is a significant global health issue, affecting an 20 million couples, or about 25% of the total, experience
estimated 60-80 million couples globally each year. infertility annually.1
According to a report by the World Health Organization

November 2024 · Volume 13 · Issue 11 Page 3432

 Patki A et al. Int J Reprod Contracept Obstet Gynecol. 2024 Nov;13(11):3432-3439

One of the leading causes of infertility among women is advantages of the 20 mg SR formulation compared to
endometriosis, a condition where tissue similar to the existing options. By exploring its potential for new
lining inside the uterus grows outside it, causing pain and indications and administration routes, this expert opinion
complications in the reproductive system.2 Endometriosis can pave the way for future research and broaden the
is known to affect 10 percent of women of reproductive therapeutic applications of dydrogesterone, particularly
age which translates to approximately 247 million females the 20 mg SR formulation, in Indian healthcare.
affected globally and 42 million women in India.3 Among
women struggling with infertility, between 25% and 50% METHODOLOGY
are found to have endometriosis. Similarly, 30% to 50% of
women diagnosed with endometriosis experience The panel included 9 experts, mainly gynaecologists, from
infertility.4 Although research indicates that women with India, who participated in an in-person expert group
endometriosis may have a higher risk of miscarriage, meeting conducted in November 2023 to discuss the role
especially recurrent pregnancy loss (RPL), defined as two of dydrogesterone in gynaecology, obstetrics, and
or more clinical pregnancy losses.5,6A recent study by Boje infertility management. Objectives and topics related to
et al found that 2.1% of women with endometriosis endometriosis, RPL, infertility and the role of
experience RPL, compared to 1.5% of women without dydrogesterone in their management were discussed, and
endometriosis.5 Polycystic ovary syndrome (PCOS) is the experts shared their views, which led to a group
another common female endocrine disorder and a leading discussion. A leading gynaecologist moderated the expert
cause of infertility, with a global prevalence ranging from group meeting and examined the existing literature and
6-26% and 3.7-22.5% in India.7 current practice with panel members to draft the expert’s
opinion. The document aimed to gather insights from
Current treatment options for endometriosis, RPL, PCOS, Indian gynaecologists ensuring relevance to address
and infertility include medical therapy, surgical specific challenges in the Indian healthcare landscape.
intervention, or a combination of both approaches. Seeking input from these specialists is vital to tailor
Management strategies for these conditions are closely approaches suited to the Indian context.
interconnected due to their overlapping
pathophysiology.4,5 Endometriosis necessitates a lifelong EXPERT OPINIONS ON DYDROGESTERONE
personalized management plan to optimize medical
treatment and minimize repeated surgeries. Treatment is Dydrogesterone in endometriosis
tailored to each woman based on her symptoms, age, and
fertility goals.8 Evidence

Dydrogesterone has a multi-faceted approach that Post-surgical outcomes for endometriosis indicate that
concurrently addresses endometriosis, PCOS, mitigates while most women experience pain relief, there remains a
RPL, and ultimately improves fertility outcomes. significant likelihood of pain recurrence. Up to 80% of
Hormonal treatment with dydrogesterone targets the women report a return of pain within two years following
pathological mechanisms of endometriosis by modulating surgery, with recurrence being more likely in severe cases.
the inflammatory environment and suppressing ectopic Hormonal treatments can inhibit the growth of endometrial
endometrial tissue proliferation. Additionally, tissue and prevent the formation of new adhesions;
dydrogesterone holds therapeutic potential for RPL by however, they do not eliminate pre-existing endometriosis
stabilizing the endometrial environment, thereby tissue.8 Despite surgical intervention being regarded as the
enhancing conditions for implantation and early primary treatment for many years, it is now recognized that
embryonic development. This stabilization is achieved repeated surgeries do not guarantee sustained
through its progestogenic activity, which supports the improvement in fertility or pain reduction. While
luteal phase and maintains an optimal endometrial endometrioma resection demonstrably improves natural
receptivity essential for successful implantation and conception rates, its impact on assisted reproductive
pregnancy maintenance.9,10 technology (ART) outcomes remains controversial.
Dydrogesterone has been shown to relieve symptoms of
NEED FOR EXPERT OPINION endometriosis and regress lesions.12 The ORCHIDEA
study found that both Dydrogesterone 10 mg 2-3 times
Endometriosis presents an escalating challenge for the daily between days 5-25 of the menstrual cycle (prolonged
medical community, as current treatments manage cyclical regimen) and continuous dydrogesterone
symptoms but fail to provide a permanent solution. There (continuous regimen) treatments significantly reduced
is a pressing need for therapies that address the underlying chronic pelvic pain (mean changes of-3.3±2.2 and -
causes of the disease.11 Dydrogesterone has established 3.0±2.2, respectively) in patients with endometriosis. Both
applications in obstetrics, gynaecology, and infertility. regimens also improved dysmenorrhea, quality of life, and
However, uncertainties surround the current use patterns sexual well-being.13 In a retrospective observational study
and the specific benefits of the 20 mg sustained release of 235 premenopausal women with chronic endometriosis
(SR) formulation. To address this gap, expert opinion is (CE) and endometrial polyps, the combination of
crucial. This approach will shed light on the current dydrogesterone and antibiotics had a cure rate of 85.2%,
landscape of dydrogesterone prescription across these compared to 74.3% with antibiotics alone, yielding an
specialties. Furthermore, experts can elucidate the distinct overall cure rate of 80.0% (188/235) (p<0.05).14

International Journal of Reproduction, Contraception, Obstetrics and Gynecology Volume 13 · Issue 11 Page 3433
 Patki A et al. Int J Reprod Contracept Obstet Gynecol. 2024 Nov;13(11):3432-3439

Expert opinion Clinical studies show that dydrogesterone can improve

pregnancy rates, extend LPS, and improve reproductive
Dydrogesterone is effective for endometriosis patients, outcomes.15 A meta-analysis shows that oral
particularly those with recurrent RPL and progesterone dydrogesterone significantly improves the chances of
resistance. In such cases, it can be administered four times ongoing pregnancy at 12 weeks (OR 1.32, p=0.0075) and
daily with extended-or sustained-release doses. Treatment live birth (OR 1.28, p=0.0214) compared to micronized
should be from day 15 to 25 of the cycle, especially if vaginal progesterone (MVP) for LPS.16
planning pregnancy.
A randomized controlled trial found that oral
Patient profile: Patients with abnormal uterine bleeding or dydrogesterone combined with vaginal progesterone for
endometriosis especially those planning for pregnancy. luteal support in intrauterine insemination (IUI) cycles
resulted in significantly higher mean serum progesterone
Target symptom: Specifically for pain management, not levels (p=0.001) and greater patient satisfaction compared
for menstrual cycle regulation. to vaginal progesterone alone. The study concluded that
oral dydrogesterone is as effective as vaginal progesterone
Dosage and application: Normally, 10 mg twice a day in for LPS in women undergoing IUI cycles.17 Recent
second half of the cycle. In cases of progesterone studies, including the 2017 and 2018 lotus I and II trials,
resistance, administer up to four times daily with have shown that oral dydrogesterone (DYD) is superior to
extended- or sustained-release doses. micronized progesterone capsules (MPC) and gel (MPG)
for LPS in fresh IVF cycles. A retrospective study of
Duration: For 15 days, followed by withdrawal of drug. women undergoing frozen embryo transfers (FETs),
revealed higher clinical pregnancy rates with oral DYD
Dydrogesterone in infertility (OR=2.87, 95% CI 1.38-6.00, p=0.005) and DYD+MPG
(OR=5.19, 95% CI 1.76-15.36, p=0.003) compared to
Evidence MPG alone.18

Following the successful trials demonstrating its efficacy Dydrogesterone optimizes luteal phase function by closely
in in-vitro fertilization (IVF) luteal phase support (LPS), mimicking natural progesterone, enhancing endometrial
dydrogesterone has gained significant traction as a receptivity for embryo implantation and early pregnancy
versatile therapeutic option in India. Its applications now development in patients undergoing FET.15,19 A study
span a broad spectrum within the fields of infertility, analysing 304 FET cycles from 241 couples found that
gynaecology, and pregnancy management. 11.8% (n=36) had serum progesterone (P4) levels below
Dydrogesterone has potential to improve patient 10 ng/ml on the day of transfer. The study concluded that
compliance, minimize side effects, and control costs. The women with low P4 levels on the day of blastocyst transfer
introduction of extended-release formulations presents a can be effectively rescued with DYD. Administering DYD
promising avenue for further enhancing treatment 10 mg three times a day to women with P4 serum levels
effectiveness. <10 ng/ml resulted in pregnancy rates beyond 12 weeks
that were comparable to those with P4 levels >10 ng/ml.20
Dydrogesterone is a synthetic progesterone that's used to
treat infertility caused by luteal phase insufficiency.
Table 1: Recommendations for dydrogesterone use in infertility based on recent guidelines.

Guideline Recommendation
Micronized progesterone and dydrogesterone are recommended to be suitable options for LPS (Level
A/ class I)
Dydrogesterone (30 mg) is recommended be a viable alternative to MVP gel in fresh ART cycles due
to its comparable efficacy and tolerability, as per the ESHRE. (Level A/ class I).
In LPS, oral dydrogesterone has advantages over other progesterone routes due to its lower cost, easy
administration, and better patient compliance in patients undergoing IUI. (Level B/ Class I).
ISAR (2022)21 Oral dydrogesterone ranging from 20 mg to 40 mg daily for LPS in women undergoing fresh embryo
transfers following IVF can be beneficial and probably recommended. (Level A/ Class I).
Progesterone supplementation, with either oral dydrogesterone or MVP, is beneficial and can be
recommended in HRT frozen embryo transfer cycles. (Level A/ class I).
Oral dydrogesterone should be a preferred choice for LPS in HRT frozen embryo transfer cycles over
the vaginal route, due to the higher tolerance, better compliance and negligible side-effects. (Level B/
class I).
Vaginal progesterone does not improve live birth rates in women with unexplained RPL. (SoR:
ESHRE
Conditional, QoE: Moderate). Justification: There is some evidence that oral dydrogesterone initiated
(2017)22
when fetal heart action can be confirmed may be effective, but more trials are needed.
ART: Assisted Reproductive Technology; ESHRE: European Society of Human Reproduction and Embryology; HRT: Hormone
Replacement Therapy; IUI: Intrauterine Insemination; IVF: In Vitro Fertilization; LPS: Luteal Phase Support; MVP: Micronized Vaginal
Progesterone; RPL: Recurrent Pregnancy Loss; SoR: Strength of Recommendation; QoE: Quality of Evidence.

International Journal of Reproduction, Contraception, Obstetrics and Gynecology Volume 13 · Issue 11 Page 3434
 Patki A et al. Int J Reprod Contracept Obstet Gynecol. 2024 Nov;13(11):3432-3439

Expert opinion successfully continued their pregnancies with oral

Dydrogesterone, while 45 patients (7.29%) experienced a
Dydrogesterone standard protocols: IUI: 10 mg twice a miscarriage before 20 weeks of gestation. The median time
day, IVF: 400 mg twice a day vaginal micronized to symptom relief was 3.32 days for low back pain, 3.9
progesterone+10 mg twice a day dydrogesterone (no days for abdominal pain, and 4.37 days for achieving
injectables favoured). Combination Therapy: haemostasis. The treatment was well-tolerated, with
Vaginal/progesterone gel (no vaginal tablet) + 10/20 mg adverse events reported in only 3.72% of patients.24 A
per day retrospective cohort study showed that progesterone
treatment is associated with an increased live birth rate in
Duration of dydrogesterone treatment: For 14 weeks, patients with RPL. After adjusting for maternal age,
extended duration up to 20 weeks, if the patient has a pregnancy loss ratio, other treatments, antiphospholipid
history of abortion or up to 32 weeks in cases of premature syndrome, and body mass index, dydrogesterone treatment
delivery. was independently linked to a higher rate of live births
compared to the control group (p=0.028).9
Use in RPL: Dydrogesterone can be used from the day of
ovulation for three months in patients with RPL who are Expert opinion
planning pregnancy before doing the IUI. In such patients,
start progesterone immediately after ovulation as per Dydrogesterone is a preferred treatment option for
ESHRE guidelines. threatened miscarriage due to its effectiveness and
favourable dosing regimen.
Dosage: Twice a day.
For threatened miscarriage:
Use of Dydrogesterone SR: Given to reduce the frequency
of doses, especially for patients already on many Dosage: Initial loading dose of 40 mg followed by 10 mg
medications. Dosage can be reduced to BD or OD with SR BD of dydrogesterone is recommended.
formulation, potentially improving patient compliance.
Duration: For 14 weeks, extended duration up to 20
In vitro fertilization–FET: For LPS in fertility treatments, weeks, if the patient has a history of abortion or up to 32
dydrogesterone (10 mg TDS) is often recommended weeks in cases of premature delivery and extended usage
alongside a multivitamin supplement (400 IU BD) to up to 18–20 weeks in twin pregnancies
enhance overall reproductive health. The use of letrozole
cycles is commonly preferred due to its effectiveness in Combination therapy: Vaginal/progesterone gel (no
stimulating ovulation. Typically, on the day of embryo vaginal tablet) + 10/20 mg dydrogesterone per day.
transfer, serum progesterone levels are expected to be in
the range of 20-30 ng/dl, indicating a well-prepared For recurrent pregnancy loss:
endometrial lining.
Dose: The recommended dosage is 10 mg twice daily
IVF treatment: Dydrogesterone 20 mg SR should be used (BD).
for sustained hormone support. Combination of vaginal
progesterone (400 mg, twice daily) and dydrogesterone Duration: Monitor the cycle and start dydrogesterone after
(10 mg, twice daily) can be used for enhanced LPS. This ovulation, continuing until 16-20 weeks of pregnancy. For
approach improves endometrial receptivity and hormone patients with a history of preterm labour, extend treatment
balance for successful implantation. until 34-36 weeks. In cases of twin pregnancies or a history
of abortion, consider extending the duration to 20 weeks.
For couples attempting natural conception, whether the
woman has PCOS or infertility issues, the following Dosage in clinical practice: Prescribed loading doses may
regimen is recommended: From day 15 to day 30 of the vary from 20 to 40 mg, with maintenance doses at 10, 20,
menstrual cycle, take dydrogesterone 10 mg twice daily. or 40 mg. Dydrogesterone administration results in
Perform a urine pregnancy test on the last day of this substantial relief from symptoms, especially low
regimen. Continue this protocol for three to six cycles to backache. A 40-mg starting dose often leads to rapid
optimize the chances of conception. cessation of bleeding (in 30-60 minutes), providing
reassurance to patients. Four tablets can be replaced with
THREATENED MISCARRIAGE AND RPL less tablets of dydrogesterone 20 mg SR to reduce the
patient anxiety and improve patient compliance.
Evidence
POLYCYSTIC OVARY SYNDROME
Dydrogesterone used for corpus luteal support has been
proven to lower the risk of pregnancy loss during the first Evidence
trimester in women experiencing threatened abortion who
do not have a history of recurrent miscarriage.23 In an In women with PCOS, progesterone is beneficial during
analysis of 617 clinical records, 572 patients (92.71%) weight loss to regulate the menstrual cycle and protect the

International Journal of Reproduction, Contraception, Obstetrics and Gynecology Volume 13 · Issue 11 Page 3435
 Patki A et al. Int J Reprod Contracept Obstet Gynecol. 2024 Nov;13(11):3432-3439

endometrium, aiding in pregnancy preparation and Pregnancy planning: Schedule a scan around day 12 to
boosting confidence during recovery. The experts check follicle readiness. Add dydrogesterone in the
recommend dydrogesterone at 10-20 mg/day, which does secretory phase to enhance pregnancy chances and make
not inhibit ovulation, administered for 10-14 days during cycles more predictable.
the second half of the menstrual cycle. For luteal support,
particularly in natural and ovulation induction Contraception: Dydrogesterone 20 mg is a viable option
pregnancies, oral progesterone preparations are preferred, for adolescent women with PCOS who are hesitant to use
with dydrogesterone at 20-40 mg/day being the favoured oral contraceptive pills. It is also effective for hormone
choice.25 A study comparing DYD and gonadotropin- replacement therapy (HRT).
releasing hormone (GnRH) antagonist protocols for
ovarian stimulation in PCOS patients undergoing freeze- PROPHYLAXIS FOR PRETERM BIRTH
all cycles showed similar numbers of mature and fertilized
oocytes between the DYD and cetrorelix (CET) groups. Evidence
Clinical pregnancy rates for the first FET cycle were also
comparable (56% for DYD vs. 55.6% for CET, p=0.283). Progesterone inhibits myometrial contraction by
No significant differences were found in biochemical regulating progesterone receptors, interfering with
pregnancy rates, implantation rates, miscarriage rates, or corticotrophin-releasing hormones, and blocking
ongoing pregnancy rates (p>0.05). Dydrogesterone- proinflammatory cytokines. In vitro studies found that
primed ovarian stimulation is a viable alternative to the progestogens, particularly dydrogesterone, inhibit
GnRH antagonist protocol for PCOS patients (Table 2).26 spontaneous myometrial contractility in a dose-dependent
manner. A randomized, double-blinded, placebo-
Table 2: Recommendations for dydrogesterone use in controlled trial evaluated the efficacy of oral
PCOS based on recent guidelines. dydrogesterone as adjunctive therapy for maintenance
treatment in preterm labour managed with tocolysis and
Guideline Recommendation corticosteroids. While the latency period, gestational age
Progestin only oral contraceptives may be at delivery, rates of preterm delivery before 34 and 37
considered for endometrial protection, weeks, pregnancy outcomes, and neonatal outcomes were
based on general population guidelines, similar between the dydrogesterone and placebo groups,
ASRM
acknowledging that evidence in women the time to recurrence of uterine contractions in
(2023)27
with PCOS is limited. (LoE: very low, participants with recurrent preterm labour was
GoR: conditional recommendation for the significantly longer in the dydrogesterone group
option. (30.6±12.3 vs. 13.7±5.0, p=0.01).28
ASRM: American Society for Reproductive Medicine; GoR:
Grade of Recommendation; LoE: Level of Evidence; PCOS: Expert opinion
Polycystic Ovary Syndrome
In cases at risk of preterm birth following IVF, patients
Expert opinion often present with spotting around 8-9 weeks. The
treatment protocol typically involves dydrogesterone,
Dydrogesterone can be used for young women with following the regimen for preterm abortion, which
amenorrhea who are planning for pregnancy and are includes loading and continuous doses. A preferred dosage
concerned about the risk of pregnancy loss due to is 20 mg twice daily, supplemented with a weekly
withdrawal medications. Dydrogesterone does not disturb progesterone injection.
ovulation, making it suitable for use starting from day 2 of
the cycle. Limitations of hydroxyprogesterone therapy: In the first
trimester, it might lead to anomalies, while in the second
Dosage: Initiate with 10 mg once daily (OD) from day 2 trimester, it may cause harm. Additionally, its use cannot
until ovulation, follow with 10 mg three times a day (TDS) be continued up to 32-34-36 weeks due to polystasis. Some
after ovulation. patients also report itching as a side effect, in which case,
injectables can be considered as an alternative.
Dydrogesterone acts synergistically with endogenous
progesterone, requiring a baseline level in the body to be PREVENTION OF PRETERM LABOUR
effective. Optimal progesterone concentration for
dydrogesterone action is around 1.5 mg per 100 ml of Evidence
blood. On day 2 of menstruation, serum progesterone
levels typically range from 0.2 to 0.4 mg per 100 ml of Dydrogesterone treatment in women at risk of pre-term
blood. A dosage of 10 mg of dydrogesterone taken twice delivery has been shown to increase the production of
daily (BD) will not inhibit ovulation. However, higher progesterone-induced blocking factor (PIBF) and
doses may have an inhibitory effect on ovulation. interleukin-10 (IL-10), while simultaneously reducing
levels of interferon-gamma (IFNγ). These changes in
immune markers suggest that dydrogesterone could be an

International Journal of Reproduction, Contraception, Obstetrics and Gynecology Volume 13 · Issue 11 Page 3436
 Patki A et al. Int J Reprod Contracept Obstet Gynecol. 2024 Nov;13(11):3432-3439

effective strategy for preventing or managing pre-term A bioequivalence study was conducted with 23 healthy
labour. By enhancing PIBF and IL-10, which are adult female subjects to compare the pharmacokinetic
associated with anti-inflammatory and immune-regulatory profiles of dydrogesterone formulations. The open-label,
effects, and reducing IFNγ, a pro-inflammatory cytokine, randomized, cross-over study evaluated a single 20 mg
dydrogesterone helps create a more favourable sustained-release dydrogesterone tablet against the
environment for sustaining pregnancy and reducing the reference formulation of 10 mg dydrogesterone tablets
risk of preterm labour.29 taken twice daily at 12-hour intervals. The objective was
to assess the rate and extent of absorption under fasting
Expert opinion conditions. The results indicated that the 20 mg sustained-
release dydrogesterone tablet is bioequivalent to the twice-
For prophylaxis of preterm labour, several strategies are daily 10 mg formulation, demonstrating similar
employed to reduce the risk of preterm birth and ensure the pharmacokinetic profiles and absorption characteristics.31
well-being of both the mother and the baby.

Prophylaxis of preterm labour often involves the use of

injection Proluton Depot once a week for 36 weeks. This
approach is also applicable in cases of multiple pregnancy
or when there is a risk of preterm labour. Dydrogesterone
is frequently prescribed alongside, typically at a dose of 10
mg thrice a day. Natural micronized progesterone is
known to have a calming effect. While the recommended
dose for this is 40 mg vaginally, experts often prefer 200
mg SR orally daily for 20 weeks in typical cases.
Continuation of progesterone therapy at this dose is
considered until 36 weeks for patients with a history of
preterm labour, previous preterm birth, suspicion of
preterm labour, or in cases of twins. Intramuscular Figure 1: Clinical advantages of dydrogesterone 20
administration may be considered if the patient mg SR compared to other synthetic progestogen
experiences nausea; otherwise, weekly injections of formulations.
hydroxyprogesterone caproate are used.
FUTURE PERSPECTIVES
HRT
The suggestions for new dydrogesterone SR products
Evidence focus on enhancing patient accessibility and convenience.
Key recommendations include reducing the cost,
Dydrogesterone exhibits superior endometrial efficacy introducing a combination pack for HRT during FET,
compared to progesterone, making it a favourable option developing an extended-release version of oestradiol
in HRT. It has a neutral impact on vascular and metabolic valerate, and retaining the current tablet size. Additionally,
systems and maintains the beneficial effects of oestradiol. experts suggest creating a gel form of dydrogesterone SR
Moreover, dydrogesterone effectively prevents and combining it with other drugs for more effective HRT.
endometrial hyperproliferation, thereby reducing the risk These changes aim to make the treatment more affordable,
of endometrial hyperplasia. These attributes collectively user-friendly, and efficient for patients.
enhance the safety and efficacy of dydrogesterone in
HRT.30 CONCLUSION

Expert opinion Endometriosis is a major cause of infertility, significantly

impacting women's reproductive health and quality of life,
Dydrogesterone is an essential component in HRT thereby necessitating effective and comprehensive
preparations due to its strong endometrial efficacy and management strategies. Dydrogesterone has shown
ability to maintain the benefits of oestradiol without efficacy for endometriosis patients, especially those with
causing endometrial hyperproliferation. Dydrogesterone is RPL and progesterone resistance, and is recommended as
cost-effective, making it an accessible option for a wide an alternative to progesterone and a component of HRT. It
range of patients. This affordability and its non-disruptive supports the luteal phase in IVF, IUI, and FET, and reduces
nature regarding ovulation make it particularly preferred the risk of threatened abortion and preterm labour.
for women planning pregnancy. Additionally, dydrogesterone helps regulate the menstrual
cycle and protect the endometrium in PCOS.
ADVANTAGES OF DYDROGESTERONE 20 MG SR
Dydrogesterone 20 mg sustained-release formulation
provides numerous advantages in clinical practice,
In clinical practice, dydrogesterone 20 mg SR offers
several advantages that enhance patient compliance and offering benefits in dosing frequency, safety, and efficacy,
treatment outcomes, as depicted in Figure 1. potentially improving patient compliance, cost-
effectiveness and treatment outcomes. This expert opinion

International Journal of Reproduction, Contraception, Obstetrics and Gynecology Volume 13 · Issue 11 Page 3437
 Patki A et al. Int J Reprod Contracept Obstet Gynecol. 2024 Nov;13(11):3432-3439

emphasizes dydrogesterone well-established safety profile 12. Peng C, Huang Y, Zhou Y. Dydrogesterone in the
and minimal androgenic/estrogenic effects, making it an treatment of endometriosis: evidence mapping and
excellent option for the long-term management of meta-analysis. Arch Gynecol Obstet.
endometriosis and related conditions. 2021;304(1):231-52.
13. Sukhikh GT, Adamyan LV, Dubrovina SO, Baranov
ACKNOWLEDGEMENTS II, Bezhenar VF, Kozachenko AV, et al. Prolonged
cyclical and continuous regimens of dydrogesterone
Authors thank IntelliMed Healthcare Solutions Pvt Ltd, are effective for reducing chronic pelvic pain in
Mumbai, for medical writing support. women with endometriosis: results of the
ORCHIDEA study. Fertil Steril. 2021;116(6):1568-
Funding: Emcure Pharmaceuticals, India 77.
Conflict of interest: None declared 14. Liu Y, Yu X, Huang J, Du C, Zhou H, Yang Y, et al.
Ethical approval: Not required Additional dydrogesterone for the treatment of
chronic endometritis treated with antibiotic in
REFERENCES premenopausal women with endometrial polyps: a
retrospective cohort study. BMC Womens Health.
1. Katole A, Saoji AV. Prevalence of Primary Infertility 2022;22:435.
and its Associated Risk Factors in Urban Population 15. Muneeba S, Acharya N, Mohammad S. The Role of
of Central India: A Community-Based Cross- Dydrogesterone in the Management of Luteal Phase
Sectional Study. Indian J Community Med Off Publ Defect: A Comprehensive Review. Cureus.
Indian Assoc Prev Soc Med. 2019;44(4):337-41. 2024;15(11):e48194.
2. Moradi Y, Shams-Beyranvand M, Khateri S, 16. Griesinger G, Blockeel C, Kahler E, Pexman-Fieth C,
Gharahjeh S, Tehrani S, Varse F, et al. A systematic Olofsson JI, Driessen S, et al. Dydrogesterone as an
review on the prevalence of endometriosis in women. oral alternative to vaginal progesterone for IVF luteal
Indian J Med Res. 2021;154(3):446-54. phase support: A systematic review and individual
3. Rozati R, Tabasum W, Ahmed MS, Khan AA, Ahmed participant data meta-analysis. PLoS ONE.
TN, Nayela S, et al. Prevalence, Surgical, and Medical 2020;15(11):e0241044.
Management of Patients with Endometriosis amongst 17. Khosravi D, Taheripanah R, Taheripanah A, Tarighat
Indian Women. Eur J Med Health Sci. 2023;5(6):101- Monfared V, Hosseini-Zijoud SM. Comparison of
6. oral dydrogesterone with vaginal progesteronefor
4. Bulletti C, Coccia ME, Battistoni S, Borini A. luteal support in IUI cycles: a randomized clinical
Endometriosis and infertility. J Assist Reprod Genet. trial. Iran J Reprod Med. 2015;13(7):433-8.
2010;27(8):441-7. 18. Vidal A, Dhakal C, Werth N, Weiss JM, Lehnick D,
5. Boje AD, Egerup P, Westergaard D, Bertelsen Kohl Schwartz AS. Supplementary dydrogesterone is
MLMF, Nyegaard M, Hartwell D, et al. beneficial as luteal phase support in artificial frozen-
Endometriosis is associated with pregnancy loss: a thawed embryo transfer cycles compared to
nationwide historical cohort study. Fertil Steril. micronized progesterone alone. Front Endocrinol.
2023;119(5):826-35. 2023;14.
6. Cohain JS, Buxbaum RE, Mankuta D. Spontaneous 19. Vuong LN, Pham TD, Le KTQ, Ly TT, Le HL,
first trimester miscarriage rates per woman among Nguyen DTN, et al. Micronized progesterone plus
parous women with 1 or more pregnancies of 24 dydrogesterone versus micronized progesterone alone
weeks or more. BMC Pregnancy Childbirth. for luteal phase support in frozen-thawed cycles
2017;17(1):437. (MIDRONE): a prospective cohort study. Hum
7. Polycystic Ovarian Syndrome (PCOS) and its Reprod Oxf Engl. 2021;36(7):1821-31.
Complications. Available at: 20. Metello J, Tomas C, Ferreira P, Santos-Ribeiro S. The
[Link] Addition of Dydrogesterone after Frozen Embryo
PRID=1893279. Accessed on 10 June 2024. Transfer in Hormonal Substituted Cycles with Low
8. Endometriosis. Available at: Progesterone Levels. RBGO Gynecol Obstet.
[Link] 2022;44(10):930.
health/faqs/endometriosis. Accessed on 31 May 2024. 21. I.S.A.R - Indian Society For Assisted Reproduction.
9. Bashiri A, Galperin G, Zeadna A, Baumfeld Y, Available at: [Link] Accessed on
Wainstock T. Increased Live Birth Rate with 14 June 2024.
Dydrogesterone among Patients with Recurrent 22. Recurrent pregnancy loss. Available at:
Pregnancy Loss Regardless of Other Treatments. J [Link]
Clin Med. 2023;12(5):1967. Legal/Guidelines/Recurrent-pregnancy-loss.
10. Ford HB, Schust DJ. Recurrent Pregnancy Loss: Accessed on 14 June 2024.
Etiology, Diagnosis, and Therapy. Rev Obstet 23. Omar MH, Mashita MK, Lim PS, Jamil MA.
Gynecol. 2009;2(2):76-83. Dydrogesterone in threatened abortion: Pregnancy
11. Mechsner S. Endometriosis, an Ongoing Pain-Step- outcome. J Steroid Biochem Mol Biol.
by-Step Treatment. J Clin Med. 2022;11(2):10. 2005;97(5):421-5.

International Journal of Reproduction, Contraception, Obstetrics and Gynecology Volume 13 · Issue 11 Page 3438
 Patki A et al. Int J Reprod Contracept Obstet Gynecol. 2024 Nov;13(11):3432-3439

24. Nagarkatti R, Mehra D, Mandal S, Dhawan A, Joshi guidance/practice-committee-

P, Nagarkatti N, et al. Real-world evaluation of safety documents/recommendations-from-the-2023-
and effectiveness of dydrogesterone in the international-evidence-based-guideline-for-the-
management of threatened abortion. Int J Reprod assessment-and-management-of-polycystic-ovary-
Contracept Obstet Gynecol. 2022;11(8):2096. syndrome/. Accessed on 14 June 2024.
25. Expert Group of Consensus on Infertility 28. Thongchan S, Phupong V. Oral dydrogesterone as an
Management and Fertility Preservation Related to adjunctive therapy in the management of preterm
Polycystic Ovary Syndrome, Reproductive labor: a randomized, double blinded, placebo‐
Endocrinology and Fertility Preservation Section of controlled trial. BMC Pregnancy Childbirth.
Chinese Society on Fertility Preservation under 2021;21(1):90.
Chinese Preventive Medicine Association, Tian QJ. 29. Hudic I, Schindler AE, Szekeres-Bartho J, Stray-
Consensus on Infertility Management and Fertility Pedersen B. Dydrogesterone and pre-term birth. Horm
Preservation Related to Polycystic Ovary Syndrome. Mol Biol Clin Investig. 2016;27(3):81-3.
Reprod Dev Med. 2020;04(04):241-50. 30. Mueck AO, Seeger H, Bühling KJ. Use of
26. Gurbuz AS, Gode F. Dydrogesterone-primed ovarian dydrogesterone in hormone replacement therapy.
stimulation is an effective alternative to gonadotropin- Maturitas. 2009;65(1):S51-60.
releasing hormone antagonist protocol for freeze-all
cycles in polycystic ovary syndrome. J Obstet Cite this article as: Patki A, Tyagi R, Khanna G,
Gynaecol Res. 2020;46(8):1403-11. Agarwal S, Vaidya R, Dalal S, et al. Recent trends on
27. Recommendations from the 2023 International dydrogesterone in gynaecology, obstetrics, and
Evidence-based Guideline for the Assessment and infertility: insights from Indian experts. Int J Reprod
Management of Polycystic Ovary Syndrome (2023). Contracept Obstet Gynecol 2024;13:3432-9.
Available at: [Link]

International Journal of Reproduction, Contraception, Obstetrics and Gynecology Volume 13 · Issue 11 Page 3439