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Prednisolone – The Fertility Wonder Drug? | Your IVF Journey. |
Prednisone fertility
Tell your doctor if you are thinking of becoming pregnant or find you are pregnant, and you are taking steroids. Because they are effective treatment, many experts now feel steroids can be taken during pregnancy as there may be a greater risk to the baby if the woman does not take effective treatment and is unwell from her IBD.
Studies suggest active IBD at the time of conception and delivery may increase adverse outcomes, including spontaneous abortion and pre-term delivery, making it important to have effective treatment for active IBD. Guidelines consider steroids taken during pregnancy to be of low risk to babies. While steroids can cross the placenta to reach the baby they rapidly become converted to less active chemicals. Experts prefer prednisone, prednisolone, and methylprednisolone since they are more efficiently broken down by the placenta than dexamethasone or betamethasone.
Maternal prednisolone doses of up to 40 mg daily are considered unlikely to affect the baby. While some studies have shown a small increase in the risk of cleft lip and palate in babies born to women taking steroids in the first three months of pregnancy, other studies have not reported this finding. Less is known about budesonide, but a small study of eight pregnant women did not find an increased risk of adverse outcomes. There have been isolated reports of babies born with adrenal suppression when mothers took steroids late in pregnancy.
So if you are taking steroids at the time of delivery be sure to let your health care team know as your baby may need a tapering course of steroids after birth. In women taking steroids for other conditions not IBD , an increase in maternal pregnancy complications such as high blood pressure and diabetes have occasionally been seen.
Much less is known about the effects of long-term steroids on male fertility and effects on their offspring. One study showed steroids can cause reversible decreases in sperm counts and motility, another found no link between steroid treatment and infertility.
Steroids are generally considered safe for use by breast feeding mothers. Although a small amount of the drug may pass to the baby, studies have found no harmful effects. Recommendations suggest that where possible women especially those on high doses should wait four hours after taking steroids before breast feeding. Search Login. Inflammatory Bowel Disease Clinic. Do steroids affect fertility, pregnancy, and breastfeeding? Steroids How effective are steroids in IBD?
How do I take it? How long should I be on steroid treatment for? Why you should not suddenly stop taking steroids? What is budesonide? Will I need to take any special precautions while being treated with steroids?
Are there alternatives to steroids? What checks will I need for long-term steroid treatment? What special information should you give your doctor?
Side effects When should I seek medical help? Should I be doing anything to protect my bones from osteoporosis? Can I take other medications along with steroids? Tell us about yourself Are you primarily a: Healthcare provider in an academic clinic. Healthcare provider in a community clinic.
❿- Pregnancy, breastfeeding and fertility while taking prednisolone tablets and liquid - NHS
Previously I had couple of blighted ovums, ruptured ectopic pregnancy and underwent many procedures but with no gain for 7 yrs. Plz can any 1 help me out with my confusion. Hi sir four months ago I had a skin disease and the doctor placed me on Prednisolone for one week but I am still on it till date will it affect my bearing children.
I am roughly 4 weeks prenant and my doc just did a vaginal ultrasound confirming we are having 2 babies.. However, while viewing the ultrasound she found a quite a bit of liquid away from the embryos and prescribed baby aspirin and meticorten 5mg… I googled this medicine and it says something about fetal development, basically negative comments. I just dont know if I should take it or not… Is it safe? I am currently 5 weeks and got prescribed the same. Can you tell me if it was beneficial for you?
Hi have been taking predinisone for the last 8 years for chest infections. Have been trying to concieve but no result of pregnancy. I have my third donor egg transfer. I do not have diabetes yet thankfully. After embryo transfer, I should take Prednisone 10mg.
Any guidance greatly appreciated and wishing you health, luck and happiness for the new year. My two babies were born healthy. Before them, I had eight miscarriages and I am thankful to God that this combo worked well for me.
I hope and prays it works out for you too. I feel so lost in this- Any information would be great. Thank you Maryan for replying. I will now see this as a sign!
Did they affect your health at all? Thank you so much for taking the time to share your experience to help me. Best wishes. Was on them for 5 days only and fell pregnant! I am now 10weeks 4days, over the moon! Id recommend these to anyone trying. It worked for me, never tried IVF due to financial difficulty was in the frame of mind if I happens it happens if not then not meant to be!
Go for it girl what do you have to lose?! My original doctor who prescribed prednisoln is now unavailable — horrible timing and my current OB has not a clue and just wants me off everything- not wise. Save my name, email, and website in this browser for the next time I comment. Prednisolone — the fertility wonder drug? Posted at h in Comment by Becky Saer 62 Comments. Ren Posted at h, 05 July Reply Hello , i just wondering this is right that doctor after IVF tell me to take 2 time a day prenisolone and how this tablets can effect my pregnacy?
Tressie Posted at h, 20 October Reply I am currently taking prednisone 20mg tablets. Pagan Posted at h, 21 March Reply I have been trying to conceive for 10 years now, I have pcos, I have never received any fertility treatment, nor have I ever been pregnant, that was until December when I fell pregnant whilst taking prednisone, sadly that pregnancy ended in miscarriage at 8 weeks.
J Posted at h, 29 May Reply It mentions that it may affect foetal growth…in what way? It seems to leave more questions that it answers. Can anyone help me with this please? Sharon Posted at h, 08 July Reply To the ladies above who are on the steroid, what dose are you on each day?
Lyn scott Posted at h, 04 August Reply 2nd round of ivf. Christine Posted at h, 13 September Reply I am on my way to Greece to have a donar egg implanted. Lauren Neuenschwander Posted at h, 18 January Reply do you mind me asking how long you stayed on it and if your dose changed? Mitu Posted at h, 12 April Reply Hi…can u tell me for how long u took prednisolone?
Kera Posted at h, 07 December Reply Amazing. Tell your doctor if you are thinking of becoming pregnant or find you are pregnant, and you are taking steroids. Because they are effective treatment, many experts now feel steroids can be taken during pregnancy as there may be a greater risk to the baby if the woman does not take effective treatment and is unwell from her IBD.
Studies suggest active IBD at the time of conception and delivery may increase adverse outcomes, including spontaneous abortion and pre-term delivery, making it important to have effective treatment for active IBD. Guidelines consider steroids taken during pregnancy to be of low risk to babies. While steroids can cross the placenta to reach the baby they rapidly become converted to less active chemicals. Experts prefer prednisone, prednisolone, and methylprednisolone since they are more efficiently broken down by the placenta than dexamethasone or betamethasone.
Maternal prednisolone doses of up to 40 mg daily are considered unlikely to affect the baby. While some studies have shown a small increase in the risk of cleft lip and palate in babies born to women taking steroids in the first three months of pregnancy, other studies have not reported this finding.
Less is known about budesonide, but a small study of eight pregnant women did not find an increased risk of adverse outcomes. There have been isolated reports of babies born with adrenal suppression when mothers took steroids late in pregnancy.
So if you are taking steroids at the time of delivery be sure to let your health care team know as your baby may need a tapering course of steroids after birth. Participants will be given the treatment of prednisone or placebo from the start of endometrial preparation till the end of the first trimester of pregnancy if pregnant.
The primary outcome is live birth rate. The results of this study will provide evidence for the effect of prednisone on pregnancy outcomes in patients with RIF. Registered on 9 October Peer Review reports. In vitro fertilization IVF is widely used and well received in couples with reproductive difficulties. However, despite the optimal use of reproductive technologies such as controlled ovarian hyper-stimulation, assisted hatching, pre-implantation genetic testing, and frozen embryo transfer , implantation remains a rate-limiting step in IVF treatment.
Recurrent implantation failure RIF refers to the clinical condition of failing to achieve a clinical pregnancy after several embryo transfers, which brings great challenges to clinicians and causes deep frustration to patients [ 3 ]. Failure of implantation can be attributed to embryo quality, endometrial receptivity, or both.
Thus, many interventions aiming at overcoming decreased endometrial receptivity have been proposed to improve pregnancy outcomes in women with RIF, but only a few are evidence-based [ 8 , 9 ].
Prednisone is a common immunomodulatory agent, which can exert a range of positive effects on the treatment of autoimmune disorders as well as the establishment of early pregnancy [ 1 , 10 ].
Studies have shown that prednisone could not only suppress uterine NK cells cytotoxicity and cytokine secretion in pre-implantation endometrium, but also stimulate the secretion of human chorionic gonadotropin hCG and promote proliferation and invasion of trophoblast [ 1 , 6 ], suggesting that prednisone may have a considerable impact on embryo implantation and IVF outcomes.
However, limited clinical trials have focused on the effect of prednisone on pregnancy outcomes. Also, the trials were either small-sized or non-randomized studies or with combined treatment regimens, which were insufficiently powered to draw a conclusion.
Therefore, multiple researchers and clinicians have called for a full-scale and well-designed randomized controlled trial RCT to clarify whether prednisone could improve pregnancy outcomes in women with RIF [ 15 ]. This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate whether the administration of prednisone could improve the live birth rate in patients with RIF. Eligible patients will be randomly assigned to the prednisone group or placebo group with a ratio.
A flowchart of the study design is illustrated in Fig. Patients will be recruited from 8 hospitals in China. The study is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The study protocol has been approved by the ethics committees at all hospitals. Infertile women with a history of RIF, which refers to the failure to achieve a clinical pregnancy under one of the following conditions with all embryos transferred being of good quality criteria of good-quality embryos are shown in Table 1 :.
Two embryo transfer cycles where the cumulative number of transferred embryos was no less than three;. Women who are currently receiving any corticosteroid or immunosuppression treatment, such as hydroxychloroquine, cyclosporine, and azathioprine.
Two months of washout period will be required prior to screening for patients on these agents;. Women who have been diagnosed with diseases affecting the uterine cavity, such as uterine malformation and submucous fibroids;. Women or their partner with abnormal chromosome karyotype not including chromosome polymorphisms ;. Women who have experienced recurrent pregnancy loss, defined by two or more failed clinical pregnancies documented by ultrasonography or histopathologic examination;.
According to the meta-analysis published in , the live birth rate was estimated to be In women with 2 or more failed embryo transfer cycles, the live birth rate varied from It is reported that the combined administration of prednisone and low molecular weight heparin or aspirin can improve live birth rate by The ratio between groups will be The minimum sample size will be for each group, for a total of participants.
All eligible subjects will be randomly assigned to one of the two study arms according to a computer-generated randomization sequence generated by the data coordinating center DCC with SAS software version 9. The randomization will be stratified according to the stage of embryo cleavage embryo or blastocyst. The randomization sequence will be kept strictly confidential by the DCC staff. Therefore, the researchers who are in charge of the enrollment have no access to the list.
Study personnel are all blinded to the upcoming treatment group allocation. The study medication both prednisone and placebo is manufactured by Xianju Pharmaceutical Co. Except for the active ingredients, the rest of the excipient and the appearance and odor are exactly the same as prednisone. The packaging of study medication both prednisone and placebo is marked according to the randomization sequence.
The packaging and tablets of prednisone and the placebo have the same appearance, which cannot be distinguished.
Therefore, the participants and all research staff do not know the allocation until the end of the study. The quality of the placebo, such as contents and bacteria contaminations, was controlled rigorously according to the GMP standard. At the screening visit, patients who have been using corticosteroid or other immunosuppression treatment will be excluded. The trial and study plan will be declared to all participants, and eligible couples who are interested in participating will sign the written informed consent.
The standardized case report forms CRFs are completed to collect current medication status and previous medical history. A physical examination height, body weight, waistline, hipline, blood pressure is performed. A total of eligible subjects will be enrolled and equally randomized into two parallel treatment arms:.
Patients will be instructed to take two tablets for once a day orally in the morning, starting with the hormone replacement regimen for endometrial preparation. Participants will undergo the frozen-thawed embryo transfer FET. If pregnancy is confirmed, the second bottle of corresponding drug will be dispensed on the day of pregnancy test and the medication will be continued till the end of the first trimester of pregnancy. If the failure of transfer or pregnancy loss occurred, the medication will be discontinued.
The remaining tablets will be returned to researchers. The endometrium is prepared with a hormone replacement cycle regimen. One blastocyst or two cleavage embryos will be transferred in each participant. All embryos transferred will be of good quality. The secondary outcomes include biochemical pregnancy, clinical pregnancy, implantation, pregnancy loss, pregnancy and perinatal complication, birth weight, congenital anomalies, and other adverse events.
The first-trimester pregnancy complications including but not limited to miscarriage, ectopic pregnancy, hyperemesis gravidarum, or gestational trophoblastic disease will be evaluated by reviewing medical records or by telephone.
The second-trimester pregnancy complications including but not limited to abortion, prenatal test results, gestational diabetes, incompetent cervix, or premature rupture of membrane will be followed up by telephone call.
The fourth follow-up time point will be at delivery. Participants will be required to notify investigators about the time of delivery. Postpartum information regarding complications of the mother including but not limited to infection, postpartum depression, late postpartum hemorrhage or the infant including but not limited to neonatal jaundice, neonatal infection, neonatal respiratory distress syndrome, neonatal hospitalization, and neonatal death will be followed up by telephone or by reviewing medical records.
During the follow-up period, adverse events and concomitant medications will be inquired and recorded every time. Participants who quit or are lost to follow-up will also be recorded.
❾-50%}Prednisone fertility.Do steroids affect fertility, pregnancy, and breastfeeding?
It's important that immune and inflammatory problems are well treated as these can affect you and your baby's wellbeing. Speak to your doctor if you become pregnant. They will discuss the risks and benefits with you and help you decide on the best treatment for you and your baby. If your doctor or health visitor says that your baby is healthy, it's OK to take prednisolone while breastfeeding.
Prednisolone passes into breast milk in small amounts. Aneuploidy in the human blastocyst. Cytogenet Genome Res. Zeyneloglu HB, Onalan G. Remedies for recurrent implantation failure.
Semin Reprod Med. Cakmak H, Taylor HS. Implantation failure: molecular mechanisms and clinical treatment. Hum Reprod Update. Corticosteroid therapy in assisted reproduction - immune suppression is a faulty premise. Hum Reprod Oxford, England.
Obstetrical outcome of anti-inflammatory and anticoagulation therapy in women with recurrent pregnancy loss or unexplained infertility. Am J Reprod Immunol.
Pathway and kinetics of prednisolone metabolism in the human placenta. J Steroid Biochem Mol Biol. Effect of prednisolone administration on patients with unexplained recurrent miscarriage and in routine intracytoplasmic sperm injection: a meta-analysis.
Prednisone pharmacokinetics during pregnancy and lactation. J Clin Pharmacol. The role of immunotherapy in in vitro fertilization: a guideline. Adjunct low-molecular-weight heparin to improve live birth rate after recurrent implantation failure: a systematic review and meta-analysis.
Administration of prednisolone and low molecular weight heparin in patients with repeated implantation failures: a cohort study. Gynecol Endocrinol. Endometrial injury in women undergoing assisted reproductive techniques. Lancet London, England. Combined treatment of prednisone and aspirin, starting before ovulation induction, may improve reproductive outcomes in ANA-positive patients. Does combined prednisolone and low molecular weight heparin have a role in unexplained implantation failure?
Arch Gynecol Obstet. Interventions for improving reproductive outcomes in women with recurrent implantation failure undergoing assisted reproductive techniques. Corticosteroids in patients with antiovarian antibodies undergoing in vitro fertilization: a prospective pilot study.
Eur J Clin Pharmacol. Download references. The authors thank all of the patients for their voluntary participation in this trial and the physicians at all study sites for referring subjects. This research did not receive any internal funding or any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
You can also search for this author in PubMed Google Scholar. YL and YS were involved in the study concept and design and in the drafting of the manuscript. DW and Z-JC contributed to the study design and critical revision of the manuscript. JY and JL contributed to the study design and revision of the manuscript. JT and YH were involved in the study concept and design and in the revision of the manuscript.
All authors read and approved the final manuscript. Correspondence to Yun Sun. Any important changes to the protocol will require a protocol amendment and must be approved by the Ethics Committee before implementation. Informed consent will be obtained from all participants prior to enrollment. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
Reprints and Permissions. Lu, Y. Prednisone for patients with recurrent implantation failure: study protocol for a double-blind, multicenter, randomized, placebo-controlled trial. Trials 21 , How do I take it? How long should I be on steroid treatment for? Why you should not suddenly stop taking steroids? What is budesonide? Will I need to take any special precautions while being treated with steroids?
Are there alternatives to steroids? What checks will I need for long-term steroid treatment? What special information should you give your doctor? But the number of participants involved was minimal, making it hard to draw firm conclusions. Other studies abound. Research in found benefits in combining Prednisone and low-dose aspirin in IVF protocols, starting three months before ovulation induction.
We certainly see this combination regularly in repeat FETs. And a study saw better ongoing pregnancy rates with the use of Prednisone, aspirin, and vitamins B and D. When prescribed to female fertility patients, Prednisolone is generally used for a short period 6 to 10 weeks. Doses vary, but 5 mg a day is common. Be wary if your clinic proposes more than 25 mg daily. Prednisolone pills are normally started on embryo transfer day or a few days earlier.
But you may be told to start them when you start your stimulating medication. Prednisolone is more often prescribed for donor-egg, donor-embryo and FET cycles.
If your HCG blood test is negative, your fertility medication, including Prednisolone, will be stopped. Your dosage may be tapered off in the final week. Like any drug, there are risks involved with taking steroids. Common side effects of Prednisolone include irritability, anxiety and sleep disturbance. Taking corticosteroids in pregnancy could also affect fetal growth. The question is, are the benefits worth the risk? It could make that crucial difference or be a dead end.
Unlike intralipids, with which it is often combined, Prednisolone pills are cheap. Prednisolone can affect your metabolism, increase the risk of diabetes and change your bone structure. Talk to your fertility clinic about Prednisolone. Until a large-scale, randomised trial is carried out, its true benefits in assisted reproduction are not clear-cut. Hello , i just wondering this is right that doctor after IVF tell me to take 2 time a day prenisolone and how this tablets can effect my pregnacy?
Hi Ren, just wondering how are you doing with your IVF? I was not made aware by my gynecologist that this was a steroid nor the side effects until I researched. I plan on going to another as there has to be a better and safer option. I am currently taking prednisone 20mg tablets. Is this safe? I have been married 16yrs, and we have been trying for 14yrs to conceive, been on numerous cycles of Clomid, had a couple of Hysterosalpingogram done, had my uterus and ovaries checked with ultrasound, every test an procedure I have done have all come back normal.
Only explanation I have been given, unexplainable, but see nothing wrong for us to conceive. In conclusion, can I continue with taking and finishing the prednisone that I am on, and engage in intercourse with my husband?
This week I should be ovulating, according to the period diary app I use. I have been trying to conceive for 10 years now, I have pcos, I have never received any fertility treatment, nor have I ever been pregnant, that was until December when I fell pregnant whilst taking prednisone, sadly that pregnancy ended in miscarriage at 8 weeks.
Back to Prednisolone tablets and liquid. You can take prednisolone while you're pregnant. It has occasionally been linked to problems in the first 12 weeks of pregnancy and possible effects on the baby's growth, however, the benefits of taking it usually outweigh any risks.
Only small amounts can cross over the placenta, so your baby is exposed to very little prednisolone in the womb. If you take prednisolone in pregnancy, your baby's growth will be checked regularly. It's important that immune and inflammatory problems are well treated as these can affect you and your baby's wellbeing.
Speak to your doctor if you become pregnant. They will discuss the risks and benefits with you and help you decide on the best treatment for you and your baby. If your doctor or health visitor says that your baby is healthy, it's OK to take prednisolone while breastfeeding. Prednisolone passes into breast milk in small amounts. It has been used for many years in breastfeeding women without side effects in their babies.
If you're taking a dose of more than 40mg of prednisolone each day for a long time, your baby may need extra monitoring. If you notice that your baby is not feeding as well as usual, or if you have any other concerns about your baby, talk to your health visitor, midwife or doctor as soon as possible.
There's no clear evidence to suggest that taking prednisolone reduces fertility in either men or women. Page last reviewed: 24 February Next review due: 24 February Pregnancy, breastfeeding and fertility while taking prednisolone tablets and liquid.
Prednisolone and pregnancy You can take prednisolone while you're pregnant. Prednisolone and breastfeeding If your doctor or health visitor says that your baby is healthy, it's OK to take prednisolone while breastfeeding. Prednisolone and fertility There's no clear evidence to suggest that taking prednisolone reduces fertility in either men or women.
Non-urgent advice: Tell your doctor if you're:.
Combined treatment of prednisone for immunosuppression and aspirin as an anti-thrombotic agent, starting before ovulation induction, may improve pregnancy. Previous data has suggested that prednisone may play a promising role Nowadays, infertility affects 8–12% of couples at reproductive age. Previous data has suggested that prednisone may play a promising role Nowadays, infertility affects 8–12% of couples at reproductive age. At a daily dose of mg, Prednisone treatment improved sperm concentration, total sperm count, and the percentage of sperm motility. Twenty-. There is ongoing interest in immune-suppressant corticosteroid drugs such as prednisolone to treat infertility in women with repeated IVF. An Australian study used low-dose Prednisolone alongside blood-thinner Clexane to try to suppress natural killer cells in women with recurrent miscarriages. It could make that crucial difference or be a dead end. Hence, the effect of prednisone in women with RIF remains controversial. Id recommend these to anyone trying. Previous data has suggested that prednisone may play a promising role in the establishment of pregnancy and help improve the pregnancy outcome in women with RIF.Trials volume 21 , Article number: Cite this article. Metrics details. Recurrent implantation failure RIF brings great challenges to clinicians and causes deep frustration to patients. Previous data has suggested that prednisone may play a promising role in the establishment of pregnancy and help improve the pregnancy outcome in women with RIF.
But there is insufficient evidence from randomized clinical trials that had adequate power to determine if prednisone can enhance live births as the primary outcome. This trial is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial ratio of prednisone versus placebo.
Participants will be given the treatment of prednisone or placebo from the start of endometrial preparation till the end of the first trimester of pregnancy if pregnant.
The primary outcome is live birth rate. The results of this study will provide evidence for the effect of prednisone on pregnancy outcomes in patients with RIF. Registered on 9 October Peer Review reports. In vitro fertilization IVF is widely used and well received in couples with reproductive difficulties. However, despite the optimal use of reproductive technologies such as controlled ovarian hyper-stimulation, assisted hatching, pre-implantation genetic testing, and frozen embryo transfer , implantation remains a rate-limiting step in IVF treatment.
Recurrent implantation failure RIF refers to the clinical condition of failing to achieve a clinical pregnancy after several embryo transfers, which brings great challenges to clinicians and causes deep frustration to patients [ 3 ]. Failure of implantation can be attributed to embryo quality, endometrial receptivity, or both.
Thus, many interventions aiming at overcoming decreased endometrial receptivity have been proposed to improve pregnancy outcomes in women with RIF, but only a few are evidence-based [ 8 , 9 ]. Prednisone is a common immunomodulatory agent, which can exert a range of positive effects on the treatment of autoimmune disorders as well as the establishment of early pregnancy [ 1 , 10 ]. Studies have shown that prednisone could not only suppress uterine NK cells cytotoxicity and cytokine secretion in pre-implantation endometrium, but also stimulate the secretion of human chorionic gonadotropin hCG and promote proliferation and invasion of trophoblast [ 1 , 6 ], suggesting that prednisone may have a considerable impact on embryo implantation and IVF outcomes.
However, limited clinical trials have focused on the effect of prednisone on pregnancy outcomes. Also, the trials were either small-sized or non-randomized studies or with combined treatment regimens, which were insufficiently powered to draw a conclusion. Therefore, multiple researchers and clinicians have called for a full-scale and well-designed randomized controlled trial RCT to clarify whether prednisone could improve pregnancy outcomes in women with RIF [ 15 ].
This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate whether the administration of prednisone could improve the live birth rate in patients with RIF. Eligible patients will be randomly assigned to the prednisone group or placebo group with a ratio. A flowchart of the study design is illustrated in Fig. Patients will be recruited from 8 hospitals in China. The study is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.
The study protocol has been approved by the ethics committees at all hospitals. Infertile women with a history of RIF, which refers to the failure to achieve a clinical pregnancy under one of the following conditions with all embryos transferred being of good quality criteria of good-quality embryos are shown in Table 1 :. Two embryo transfer cycles where the cumulative number of transferred embryos was no less than three;.
Women who are currently receiving any corticosteroid or immunosuppression treatment, such as hydroxychloroquine, cyclosporine, and azathioprine.
Two months of washout period will be required prior to screening for patients on these agents;. Women who have been diagnosed with diseases affecting the uterine cavity, such as uterine malformation and submucous fibroids;.
Women or their partner with abnormal chromosome karyotype not including chromosome polymorphisms ;. Women who have experienced recurrent pregnancy loss, defined by two or more failed clinical pregnancies documented by ultrasonography or histopathologic examination;. According to the meta-analysis published in , the live birth rate was estimated to be In women with 2 or more failed embryo transfer cycles, the live birth rate varied from It is reported that the combined administration of prednisone and low molecular weight heparin or aspirin can improve live birth rate by The ratio between groups will be The minimum sample size will be for each group, for a total of participants.
All eligible subjects will be randomly assigned to one of the two study arms according to a computer-generated randomization sequence generated by the data coordinating center DCC with SAS software version 9.
The randomization will be stratified according to the stage of embryo cleavage embryo or blastocyst. The randomization sequence will be kept strictly confidential by the DCC staff. Therefore, the researchers who are in charge of the enrollment have no access to the list. Study personnel are all blinded to the upcoming treatment group allocation. The study medication both prednisone and placebo is manufactured by Xianju Pharmaceutical Co.
Except for the active ingredients, the rest of the excipient and the appearance and odor are exactly the same as prednisone. The packaging of study medication both prednisone and placebo is marked according to the randomization sequence. The packaging and tablets of prednisone and the placebo have the same appearance, which cannot be distinguished.
Therefore, the participants and all research staff do not know the allocation until the end of the study. The quality of the placebo, such as contents and bacteria contaminations, was controlled rigorously according to the GMP standard.
At the screening visit, patients who have been using corticosteroid or other immunosuppression treatment will be excluded. The trial and study plan will be declared to all participants, and eligible couples who are interested in participating will sign the written informed consent.
The standardized case report forms CRFs are completed to collect current medication status and previous medical history.
A physical examination height, body weight, waistline, hipline, blood pressure is performed. A total of eligible subjects will be enrolled and equally randomized into two parallel treatment arms:. Patients will be instructed to take two tablets for once a day orally in the morning, starting with the hormone replacement regimen for endometrial preparation.
Participants will undergo the frozen-thawed embryo transfer FET. If pregnancy is confirmed, the second bottle of corresponding drug will be dispensed on the day of pregnancy test and the medication will be continued till the end of the first trimester of pregnancy.
If the failure of transfer or pregnancy loss occurred, the medication will be discontinued. The remaining tablets will be returned to researchers. The endometrium is prepared with a hormone replacement cycle regimen. One blastocyst or two cleavage embryos will be transferred in each participant.
All embryos transferred will be of good quality. The secondary outcomes include biochemical pregnancy, clinical pregnancy, implantation, pregnancy loss, pregnancy and perinatal complication, birth weight, congenital anomalies, and other adverse events. The first-trimester pregnancy complications including but not limited to miscarriage, ectopic pregnancy, hyperemesis gravidarum, or gestational trophoblastic disease will be evaluated by reviewing medical records or by telephone.
The second-trimester pregnancy complications including but not limited to abortion, prenatal test results, gestational diabetes, incompetent cervix, or premature rupture of membrane will be followed up by telephone call. The fourth follow-up time point will be at delivery. Participants will be required to notify investigators about the time of delivery. Postpartum information regarding complications of the mother including but not limited to infection, postpartum depression, late postpartum hemorrhage or the infant including but not limited to neonatal jaundice, neonatal infection, neonatal respiratory distress syndrome, neonatal hospitalization, and neonatal death will be followed up by telephone or by reviewing medical records.
During the follow-up period, adverse events and concomitant medications will be inquired and recorded every time. Participants who quit or are lost to follow-up will also be recorded. All AEs will be assessed and recorded in detail. The ethics committee will determine whether the AE or SAE is likely to be associated with the study medication and whether it is necessary to break blinding codes.
All of the investigators including physicians, nurses, and research assistants will attend a training workshop before the starting of the trial, to ensure the accuracy of outcome assessments and data collection. A protocol and standard operation procedures will be given to every investigator. The DCC is responsible for the monitoring tasks of the trial.
The DCC and personnel of Ren Ji hospital will check the authenticity, accuracy, and integrity of the data from different sites regularly to ensure the quality of the collected data. The data will be analyzed by SPSS The analysis will be conducted using intention-to-treat principles. The primary outcome, live birth rate, will be compared between two groups by the Pearson chi-square test. Secondary outcomes, such as rates of pregnancy and implantation, will be analyzed using the Pearson chi-square test.
A per-protocol analysis will be performed according to the actual participants completing the entire trial. As a secondary analysis, we will fit a generalized linear mixed effect model with a logit link to compare the treatment arms with respect to the primary outcome of live birth, and binary secondary outcomes e. A random intercept will be included to adjust for the correlation among patients within center.
We plan to enroll subjects from 8 hospitals in China. The enrollment began in November At the time of manuscript preparation, more than subjects have been enrolled. The result of this multicenter randomized trial will provide valid evidence for the effect of prednisone on pregnancy outcomes in women with RIF.
We speculate that the administration of prednisone may improve live birth rate in patients with RIF. As we all know, there is as yet no universally accepted definition of RIF [ 2 ]. Different descriptions were based on the number of previously failed cycles or the number of embryos transferred or a combination of both. Lukasz et al. It is suggested to define RIF as the absence of implantation after two treatment cycles where the cumulative number of transferred embryos was no less than four for cleavage-stage embryos and no less than two for blastocysts, and all of the embryos transferred should be of good quality [ 4 ].
There are limited clinical trials assessing the efficacy of prednisone in patients with implantation failure. A quasi-randomized, controlled trial conducted in women with previously one or two failed ICSI attempts suggested a combination of prednisolone and low molecular weight heparin LMWH might have a positive effect on pregnancy and implantation rates [ 21 ]. A prospective pilot study confirmed that prednisolone was useful in patients with at least two previous IVF failures and serum antiovarian antibody [ 23 ].
Hence, the effect of prednisone in women with RIF remains controversial. Despite lacking of convincing evidence, prednisone is being used by more and more IVF centers and reproductive physicians all across the world.
There is an urgent need for a well-designed, adequately powered RCT to prove the efficacy of prednisone in patients with RIF.
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