Prednisolone – The Fertility Wonder Drug? | Your IVF Journey.

Looking for:














































   

 

.



  Abstract. BACKGROUND: Glucocorticoids have been used in conjunction with zona dissection to improve pregnancy and implantation rates in IVF patients. We examined the impact of use of corticosteroids prior to embryo transfer in embryo transfers in women with CD and UC, and our overall. or prednisone during frozen embryo transfer cycle for patients with past implantation failure and elevated peripheral Th1/Th2 ratio improved. ❿  


- Prednisone and frozen embryo transfer



 

Ubaldi, L. Rienzi, S. Ferrero, R. Anniballo, M. Iacobelli, L. Cobellis, E. The aim of this prospective randomized study was to evaluate the effect of low-dose prednisolone in addition to the standard protocol, on pregnancy and implantation rates in routine ICSI patients before and after embryo replacement. In the last decade, conflicting results have been published concerning the use of glucocorticoids during and after embryo transfer, administered with the aim of improving implantation and ongoing pregnancy rates Kemeter and Feichtinger, ; Cohen et al.

Glucocorticoids have been used in IVF patients who had zona-dissected embryo replacement Cohen et al.

These authors hypothesized that breaching the protective coating of the zona pellucida could expose the embryos to bacteria or leukocyte infiltration.

The immunosuppression caused by glucocorticoid administration probably decreases the presence of uterine lymphocytes and of peripheral immune cells especially segmented neutrophils that could invade and destroy the zona-dissected embryos.

Similar results were reported when assisted hatching was introduced Cohen et al. These results suggested that immunosuppression could have also improved pregnancy rates in routine IVF—embryo transfer patients. Several reasons could support the use of glucocorticoids in non-micromanipulated embryos. It was suggested that the use of glucocorticoids in normo-androgenic normo-ovulating women during a stressful condition such as the IVF—embryo transfer treatment could reduce adrenal gland activity, preventing hyperandrogenaemia Howels et al.

However, these results were not confirmed Rein et al. A complex interaction between the embryo and the endometrium involves hormones, growth factors, epithelial cells, stromal cells, leucocytes and the intervening extracellular matrix Armant and Diaz, Glucocorticoids may have important effects on these components, modulating the early events of the implantation process Finlay and Cristofalo, ; Dean et al. Several investigators studied the role of natural killer NK cells in human implantation Beer et al.

Women with recurrent abortion and infertile women with many previous failed IVF attempts, have elevated levels of peripheral and endometrial NK cells Beer et al. A reduction of peripheral NK cells after 3 days of 20 mg prednisolone administration has been reported Pountain et al. Hasegawa et al. These authors suggested that since this dosage is too low to reduce autoantibody titres, the increased implantation rates observed could be derived from the anti-inflammatory action of the glucocorticoids through the reduction of NK cells Hasegawa et al.

Another possible benefit of the use of glucocorticoids could be due to their anti-inflammatory action exerted at the level of the endometrium. The uterine environment could be compromised by the embryo transfer technique. The stimulus of an intrauterine catheter may initiate some inflammatory response that could be correlated to the technique of the embryo transfer itself Hill, In the present prospective randomized study, we evaluated the implantation and clinical pregnancy rates in routine ICSI patients treated with prednisolone in addition to the standard protocol before and after embryo replacement.

Patients were excluded if they had contraindications for glucocorticoid therapy. In group A, prednisolone was started on day 1 of controlled ovarian hyperstimulation and continued for 4 weeks. All patients were counselled regarding the ICSI procedure and they gave their informed consent to enter the study.

This study was given approval by the ethical committee of the European Hospital, Rome. In all cycles ovarian stimulation was carried out by the association of GnRH agonist s. Administration of the agonist was started on day 21 of the menstrual cycle with a s. Thereafter, the rFSH dose was adapted individually according to the serum E 2 increment and ultrasound measurements of follicular diameter.

Oocyte retrieval was performed 36 hours after HCG administration under transvaginal ultrasound-guided puncture of the follicles. Oocyte and ejaculated semen preparation as well as the ICSI procedure have been extensively described elsewhere Rienzi et al. Fertilization was considered normal when two clearly distinct pronuclei PN were present. Further embryonic development was assessed 24 hours later. The embryos were classified according to the following morphological criteria.

Type A or excellent embryos are defined as embryos in which all blastomeres have an equal or non-equal size without fragmentation. All patients received also aspirin Aspirinetta 0. Prontogest mg; Amsa, Barberino del Mugello, Italy. Treatment was started on the day of oocyte retrieval. Pregnancy was confirmed by a serial rise in serum HCG concentration on two consecutive occasions, 12 days after embryo replacement.

Clinical pregnancy was determined by ultrasound demonstration of cardiac activity at 7 weeks. Of a total of patients selected who underwent cycles, patients in cycles received at least two embryos and completed the study.

A total of 45 cycles were excluded from the study: 10 cycles were cancelled because of a poor ovarian response, in three cycles HCG was not given to trigger ovulation because of the high risk of severe ovarian hyperstimulation and in 32 cycles less than two embryos were replaced. The treated patients reported no side-effects. Table I presents patient characteristics. There were no statistically significant differences between groups. The mean age was Day 3 FSH serum level 6.

ICSI results were also similar between groups with a mean number of metaphase II oocytes retrieved of The clinical outcome of prednisolone treatment is given in Table II. No significant differences were found between the two groups in any of the clinical outcome parameters.

The use of glucocorticoids before and after embryo transfer has been proposed with the aim of improving pregnancy and implantation. However, so far, conflicting data have been published Kemeter and Feichtinger ; Cohen et al. In this prospective randomized study we used a low dose of prednisolone for four weeks in order to induce and maintain an anti-inflammatory control according to the data previously reported Birkenfeld et al.

Only patients with a normal ovarian response were included in the current study. Poor responders less than three follicles were excluded because the clinical results could be impaired in these patients Levi et al.

All patients also received aspirin at the dose of mg per day starting from day 1 of stimulation and continued for at least 4 weeks. Higher numbers of follicles and oocytes retrieved and higher implantation and pregnancy rates in patients treated with aspirin have been reported Rubinstein et al. Low-dose aspirin inhibits the cyclo-oxygenase enzyme which converts arachinodate into thromboxane A 2 TXA 2 avoiding vasoconstriction and platelet aggregation Burch and Stanford, We observed comparable clinical pregnancy Our data are in accordance with those recently reported Bider et al.

These authors demonstrated in a randomized prospective non-placebo study that the administration of low-dose long-acting glucocorticoids 0. Even doubling the dose of glucocorticoids 1 mg dexamethasone did not result in a statistically significant increase of the implantation or pregnancy rates in the group of glucocorticoids-treated patients Bider et al. Similar results had been already reported by other authors Lee et al.

However, a few years earlier, Polak de Fried et al. There are several differences between this latter study and our study or the above-mentioned studies Lee et al. The study by Polak de Fried et al. With regard to the dosage administered, in our study we used a much lower dose of glucocorticoids compared with that used in the study carried out by Polak de Fried et al. However, low doses of glucocorticoids produce the same degree of neutrophilia and lymphocytopoenia as the higher doses Claman, The pregnancy and implantation rates reported by Polak de Fried et al.

Therefore, it seems that the use of glucocorticoids may be useful in raising a low pregnancy and implantation rate rather than increasing standard clinical results. In summary, in the present prospective randomized study we did not observe any differences with regard to the implantation and clinical pregnancy rates in routine ICSI patients treated with low-dose prednisolone in addition to the standard protocol before and after embryo replacement.

The use of glucocorticoids maybe useful in the case of sub-optimal embryonic or uterine conditions, but it seems that they are not able to increase embryo development or uterine receptivity in standard laboratory and clinical conditions.

Comparison of cycle characteristics, hormonal profile and ICSI outcome between patients treated with and without prednisolone. Comparison of the clinical outcome between patients treated with and without prednisolone. E-mail: ubaldi. Armant, D.

In Seil, M. A Comprehensive Text of Reproductive Technology. Beer, A. Bider, D. Birkenfeld, A. Burch, J. Claman, H. July, — Cohen, J. Dean, D. Durant, S. Hasseid, J. Finlay, C. Hasegawa, I. Hill, J. Howels, C. Lancetii— Kemeter, P.

    ❾-50%}

 



    JY and JL contributed to the study design and revision of the manuscript.

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.

This study is expected to provide a reliable answer. The study enrollment began on 20 November and is expected to end in June The enrollment is ongoing at the time of manuscript submission. The trial protocol is version 3. The datasets generated during the current study are available from the corresponding author on reasonable request.

Novel immunotherapeutic approaches for treatment of infertility. Biomed Pharmacother. The stimulus of an intrauterine catheter may initiate some inflammatory response that could be correlated to the technique of the embryo transfer itself Hill, In the present prospective randomized study, we evaluated the implantation and clinical pregnancy rates in routine ICSI patients treated with prednisolone in addition to the standard protocol before and after embryo replacement.

Patients were excluded if they had contraindications for glucocorticoid therapy. In group A, prednisolone was started on day 1 of controlled ovarian hyperstimulation and continued for 4 weeks. All patients were counselled regarding the ICSI procedure and they gave their informed consent to enter the study. This study was given approval by the ethical committee of the European Hospital, Rome. In all cycles ovarian stimulation was carried out by the association of GnRH agonist s.

Administration of the agonist was started on day 21 of the menstrual cycle with a s. Thereafter, the rFSH dose was adapted individually according to the serum E 2 increment and ultrasound measurements of follicular diameter. Oocyte retrieval was performed 36 hours after HCG administration under transvaginal ultrasound-guided puncture of the follicles. Oocyte and ejaculated semen preparation as well as the ICSI procedure have been extensively described elsewhere Rienzi et al.

Fertilization was considered normal when two clearly distinct pronuclei PN were present. Further embryonic development was assessed 24 hours later. The embryos were classified according to the following morphological criteria. Type A or excellent embryos are defined as embryos in which all blastomeres have an equal or non-equal size without fragmentation. All patients received also aspirin Aspirinetta 0.

Prontogest mg; Amsa, Barberino del Mugello, Italy. Treatment was started on the day of oocyte retrieval. Pregnancy was confirmed by a serial rise in serum HCG concentration on two consecutive occasions, 12 days after embryo replacement. Clinical pregnancy was determined by ultrasound demonstration of cardiac activity at 7 weeks.

Of a total of patients selected who underwent cycles, patients in cycles received at least two embryos and completed the study. A total of 45 cycles were excluded from the study: 10 cycles were cancelled because of a poor ovarian response, in three cycles HCG was not given to trigger ovulation because of the high risk of severe ovarian hyperstimulation and in 32 cycles less than two embryos were replaced.

The treated patients reported no side-effects. Table I presents patient characteristics. There were no statistically significant differences between groups. The mean age was Day 3 FSH serum level 6. ICSI results were also similar between groups with a mean number of metaphase II oocytes retrieved of The clinical outcome of prednisolone treatment is given in Table II.

No significant differences were found between the two groups in any of the clinical outcome parameters. The use of glucocorticoids before and after embryo transfer has been proposed with the aim of improving pregnancy and implantation.

However, so far, conflicting data have been published Kemeter and Feichtinger ; Cohen et al. In this prospective randomized study we used a low dose of prednisolone for four weeks in order to induce and maintain an anti-inflammatory control according to the data previously reported Birkenfeld et al. Only patients with a normal ovarian response were included in the current study. Poor responders less than three follicles were excluded because the clinical results could be impaired in these patients Levi et al.

All patients also received aspirin at the dose of mg per day starting from day 1 of stimulation and continued for at least 4 weeks. Higher numbers of follicles and oocytes retrieved and higher implantation and pregnancy rates in patients treated with aspirin have been reported Rubinstein et al. Low-dose aspirin inhibits the cyclo-oxygenase enzyme which converts arachinodate into thromboxane A 2 TXA 2 avoiding vasoconstriction and platelet aggregation Burch and Stanford, We observed comparable clinical pregnancy Our data are in accordance with those recently reported Bider et al.

These authors demonstrated in a randomized prospective non-placebo study that the administration of low-dose long-acting glucocorticoids 0. Even doubling the dose of glucocorticoids 1 mg dexamethasone did not result in a statistically significant increase of the implantation or pregnancy rates in the group of glucocorticoids-treated patients Bider et al. Similar results had been already reported by other authors Lee et al.

However, a few years earlier, Polak de Fried et al. There are several differences between this latter study and our study or the above-mentioned studies Lee et al. The study by Polak de Fried et al. With regard to the dosage administered, in our study we used a much lower dose of glucocorticoids compared with that used in the study carried out by Polak de Fried et al.

However, low doses of glucocorticoids produce the same degree of neutrophilia and lymphocytopoenia as the higher doses Claman, The pregnancy and implantation rates reported by Polak de Fried et al.

Therefore, it seems that the use of glucocorticoids may be useful in raising a low pregnancy and implantation rate rather than increasing standard clinical results. In summary, in the present prospective randomized study we did not observe any differences with regard to the implantation and clinical pregnancy rates in routine ICSI patients treated with low-dose prednisolone in addition to the standard protocol before and after embryo replacement.

The use of glucocorticoids maybe useful in the case of sub-optimal embryonic or uterine conditions, but it seems that they are not able to increase embryo development or uterine receptivity in standard laboratory and clinical conditions. Comparison of cycle characteristics, hormonal profile and ICSI outcome between patients treated with and without prednisolone. Comparison of the clinical outcome between patients treated with and without prednisolone.

E-mail: ubaldi. Armant, D. In Seil, M. A Comprehensive Text of Reproductive Technology. Beer, A. Bider, D. Birkenfeld, A. Burch, J. Claman, H. July, — Cohen, J. Dean, D. Durant, S. Hasseid, J. Finlay, C. Hasegawa, I. Hill, J. Howels, C. Lancet , ii , — Kemeter, P. A prospective randomized study. Fertilitat , 2 , 71 — Lachapelle, M. Lee, K. Levi, A.

When it comes to fertility medication, some are more controversial than others. A steroid called Prednisolone, or Prednisone, is one of them. Some call it a fertility wonder drug. Others are more sceptical. So is it worth trying or a waste of money?

Prednisolone is a form of corticosteroid sometimes prescribed to fertility patients with recurrent miscarriageelevated natural killer NK cells or implantation issues. Prednisolone is basically a synthetic hormone that helps suppress immune responses. As an anti-inflammatory and immuno-suppressant, it can treat a range of other conditions.

These include allergies, blood disorders, respiratory problems skin problems and sperm antibodies. But while Prednisolone is well regarded in general medicine, the jury is out on its tangible benefits to fertility patients.

IVF consultant Lord Winston is distinctly wary of it. Most are small-scale. An Australian study used low-dose Prednisolone alongside blood-thinner Clexane to try to suppress natural killer cells in women with recurrent miscarriages. The results were quite promising. 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.

Helloi 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. I was only in Prednisone for 10 days for a chest infection so I never expected it would help me get pregnant.

I have told my doctor that when I got pregnant I was on prednisone but they refuse to prescribe it me and they are well aware of my struggle to get pregnant. I have not been able to get pregnant since, no offer of help or any interest from Doctors of my fertility. If ever there comes up any trials to help women get pregnant on prednisone then I would happily put myself forward for it. I am saving up for surrogacy but if I can get pregnant naturally by taking prednisone then I would happily go for It.

Hi pagan, M Dr Devendra from India. I m a gynecologist. I want to tell u one thing if u have got pregnant once half d battle u have won…it means there is nothing wrong in d process of fertilization and implantation. The use of prednisone and baby aspirin and Lovenox has been a game changer for so many women with failed attempts including myself. Hi Jen, I just read your comment.

Did you use all 3 prior to pregnancy — aspirin, prednisone and clovox? Did your gynecologist prescribed them? With prednisone do your remember how long you had to take it for? My Fertility doc has put me on it after egg retrieval. If you go to a fertility doctor they will prescribe it. You can also request it for other reasons like skin conditions and allergies. Then just try to get pregnant. Also seeing a naturopath that specializes in Fertility will help.

Wondering if I should go for another cycle! This time prescribed predisinfection, aspirin, estrofem and progesterone but not folic acid. Just wondering whether it is still OK to take the pregnacare vitamin and folic acid supplements? I am on my way to Greece to have a donar egg implanted.

I am on Prednisolone as well has having intralipid infusions. This is my 5 time so am hoping is all works this time. Hi Christine.

I was just wondering if you were successful and why you chose Greece. I am Greek by the way! He looked at my ovulation temperature charts, and put me on Prednisolone 2. Three years later I went back on same dose and got pregnant the first month. I know that I should take two weeks more but after that should decrease 5 Mg per day said my doctor. Hi I conceived in 3rd ivf cycle. 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?

Prednisolone (or Prednisone) is often prescribed to fertility patients. But can it really prevent miscarriage and boost implantation rates? Combined treatment of prednisone and hydroxychloroquine may improve outcomes of frozen embryo transfer in antinuclear antibody-positive patients. ( ratio of prednisone versus placebo). Infertile patients with RIF who intend to undergo frozen-thawed embryo transfer (FET) after in vitro fertilization. Abstract. BACKGROUND: Glucocorticoids have been used in conjunction with zona dissection to improve pregnancy and implantation rates in IVF patients. After one month of treatment, the above immune indicators were tested, and natural cycle frozen embryo transfer was performed. Lee, K. Discussion The results of this study will provide evidence for the effect of prednisone on pregnancy outcomes in patients with RIF. Christine Posted at h, 13 September Reply I am on my way to Greece to have a donar egg implanted. The DCC is responsible for the monitoring tasks of the trial.

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.



Comments

Popular posts from this blog

Prednisone dosing for copd exacerbation

Hydroquinone + Mometasone + Tretinoin: View Uses, Side Effects and Medicines | 1mg - Can hydroquinone and retinols safely be combined?