Route Of Progesterone Administration Research Articles

P-412 Elevated progesterone levels after hormone replacement therapy (HRT) for frozen embryo transfer (FET) does not impair IVF outcomes, a retrospective study

Abstract Study question Does high serum progesterone (P) level on the day of FET after hormone replacement therapy affect IVF outcomes? Summary answer The supraphysiological serum progesterone levels on the day of FET after HRT do not impair reproductive outcomes. What is known already A proper synchronization between embryo and the endometrium is still required by controlling the timing and the dosage of exposure to exogenous hormones. Previous observational studies have highlighted the negative effects of serum hormone levels at the minimum threshold during FET cycles. However, based on existing research, the relationship between progesterone levels on FET day and pregnancy outcomes as well as the certain dose of progesterone ideally to achieve pregnancy and a live birth are debatable topics Study design, size, duration This is an observational, retrospective and cohort study including 7539 FET cycles that were performed under artificial endometrial preparation with HRT using exogenous estradiol and progesterone (vaginal, subcutaneous and intramuscular) between January 2017 and December 2022. Both euploid FET from autologous oocyte ICSI-PGT-A cycles (n = 1822) or FET from ICSI cycles using donated oocytes (n = 5724) were considered. Participants/materials, setting, methods Women were divided into three groups according to P4 level on the day of FET:P<20 ng/ml (n = 6623),P≥20-40 ng/ml (n = 770) and P > 40 ng/ml (n = 146).All ET were performed at the blastocyst stage.The primary outcome was live birth rate (LBR). Secondary outcomes evaluated were biochemical, clinical, and ongoing pregnancy, and miscarriage rate (MR) calculated per FET.Categorical variables were compared between groups with Fisher’s exact test. Logistic regression models adjusted (AOR) with several confounders. Main results and the role of chance There were no significant differences in baseline characteristics of the study population. The mean of P4 level was 15,66 ng/ml. Female age was P < 20:38.7 ±3.1, P ≥ 20-40: 39.0 ±3.0, and P > 40: 38.1 ±2.9 (p = 0.53) years old. The group with the highest progesterone levels always found lower biochemical pregnancy even no statistically significant [64.6% (P < 20) vs 63.7% (P ≥ 20-<40) vs 61.1% (P > 40); p = 0.62]; in clinical pregnancy [56.3% (P < 20) vs 56.8% (P ≥ 20-<40) vs 51.4% (P > 40); p = 0.5] and in ongoing [47.0% (P < 20) vs 47.0% (P ≥ 20-<40) vs 41.8% (P > 40); p = 0.47] pregnancy rates. The MR was also higher in the group with higher progesterone, although not significantly: 16.2% (P < 20) vs 15.0% (P ≥ 20-<40) vs 18.0% (P > 40) (p = 0.60). No statistically significant differences were reported for live birth rate, 41.8% (P < 20) vs 40.3% (P ≥ 20-<40) vs 34.2% (P > 40) (p = 0.2). The multivariate analysis showed an increased risk of miscarriage when P > 40ng/ml, aOR= 1.14 (0.75-1.74) (p = 0.55) whereas no such association was found with P4 ≥20-40 ng/ml, aOR=0.92 (0.74-1.15) (p = 0.46). Additionally, the probability of live birth is similar when the patient was P > 40 (aOR= 0.77 (0.51-1,15) (p = 0.20)) than when P ≥ 20-<40 (aOR=0.94 (0.79-1,11) (p = 0.47) compared with the references group. Limitations, reasons for caution The retrospective design and different female factors for IVF were included in the study leading to a possible biased population although the adjusted analysis. Different routes of progesterone administration were considered in the study. Currently, we don’t report the timing between the last P4 administration and dosage on the FET. Wider implications of the findings This information is useful for clinicians who monitor progesterone levels prior to FET to avoid reaching high levels that would undermine the chances of achieving a newborn. Trial registration number Not Applicable

Maternal and Neonatal Outcomes Associated With Route of Progesterone Administration in Pregnancies Following a Single Euploid Frozen Embryo Transfer

Maternal and Neonatal Outcomes Associated With Route of Progesterone Administration in Pregnancies Following a Single Euploid Frozen Embryo Transfer

982 Maternal and neonatal outcomes associated with route of progesterone administration in frozen embryo transfers

982 Maternal and neonatal outcomes associated with route of progesterone administration in frozen embryo transfers

Individualized luteal phase support based on serum progesterone levels before embryo transfer in frozen-thawed embryo transfer cycles: comparison of different routes of progesterone administration

Individualized luteal phase support based on serum progesterone levels before embryo transfer in frozen-thawed embryo transfer cycles: comparison of different routes of progesterone administration

P-511 Prolonging the time of vaginal progesterone supplementation does not improve pregnancy outcomes after day 6 blastocyst transfer

Abstract Study question Does the administration of vaginal progesterone for 6 days improve pregnancy outcomes when transferring day 6 blastocysts, as opposed to 5 days of progesterone treatment? Summary answer We observed similar pregnancy outcomes after 5 and 6 days of vaginal progesterone supplementation following day 6 blastocyst transfer in oocyte recipient cycles. What is known already Progesterone administration promotes the final phase of endometrial preparation for embryo transfer. However, the optimal duration of progesterone transformation still remains unknown. The implantation potential of blastocysts formed at different timepoints is also contentious, as blastocysts on day 6 have been linked to poorer clinical outcomes compared to their day 5 counterparts. It is unclear whether this effect stems from an intrinsic impaired implantation capacity of slow-developing blastocysts, or a displaced window of implantation (WOI). It has been hypothesized that 6 days of progesterone administration may improve clinical outcomes after frozen day 6 blastocyst transfer. Study design, size, duration Retrospective cohort study of oocyte recipients undergoing single day 6 blastocyst transfer, between January 2020 and December 2022. This study compared two groups: day 6 blastocysts transferred after 5 days of progesterone administration (n = 284) and day 6 embryo transfers performed after 6 days of progesterone administration (n = 69). Participants/materials, setting, methods Our study included oocyte recipients who underwent a single embryo transfer of a day 6 blastocyst and hormonal replacement treatment for endometrial preparation with vaginal external progesterone administration (800mg/24h) for either 5 or 6 days prior to embryo transfer. Outcomes were analyzed using unpaired t-test or Fisher’s test and logistic regression. Multivariate models were adjusted for oral or transdermal estrogen administration and endometrial thickness on the day of embryo transfer. P-values <0.05 were considered significant. Main results and the role of chance Mean maternal age was 43.5 years, while patients had a mean BMI of 25.1. Mean days of estrogen therapy prior to embryo transfer were 22.4, with 75.3% of patients using transdermal estrogen administration, and achieving a mean endometrial thickness of 9.6 mm on the day of transfer. Mean progesterone levels on the day of transfer were 11.9 ng/ml. Thirty-seven percent of the day 6 blastocysts were of high quality. None of the demographic or cycle characteristics were significantly different between the study groups. When considering outcomes of day 6 blastocyst transfers, we found no significant differences in biochemical (26.33% vs 20.13%, p = 0.343), clinical (22.06% vs 17.46%, p = 0.49) and ongoing (14.64% vs 9.52%, p = 0.41) pregnancy rates between 5 and 6 days of progesterone administration. Our adjusted analysis further corroborated these results. Limitations, reasons for caution The retrospective nature of the study and low number of transfers performed after 6 days of progesterone treatment warrant careful interpretation. This study only evaluated endometrial preparation by vaginal progesterone administration in oocyte recipients and cannot be extrapolated to other routes of progesterone administration or other patient populations. Wider implications of the findings Poorer reproductive outcomes associated with the transfer of day 6 blastocysts appear to be related to a reduced implantation capacity of slow-developing embryos rather than a displaced WOI due to rising progesterone. WOI appears wider than assumed, as prolonged progesterone transformation times had no effect on pregnancy outcomes. Trial registration number Not applicable

Comparison of the efficacy of subcutaneous versus vaginal progesterone using a rescue protocol in vitrified blastocyst transfer cycles

Does administration of subcutaneous (s.c.) progesterone support ongoing pregnancy rates (OPR) similar to vaginal progesterone using a rescue protocol in hormone replacement therapy frozen embryo transfer cycles? Retrospective cohort study. Two sequential cohorts - vaginal progesterone gel (December 2019-October 2021; n=474) and s.c. progesterone (November 2021-November 2022; n=249) -were compared. Following oestrogen priming, s.c. progesterone 25 mg twice daily (b.d.) or vaginal progesterone gel 90 mg b.d. was administered. Serum progesterone was measured 1 day prior to warmed blastocyst transfer (i.e. day 5 of progesterone administration). In patients with serum progesterone concentrations <8.75 ng/ml, additional s.c. progesterone (rescue protocol; 25 mg) was provided. In the vaginal progesterone gel group, 15.8% of patients had serum progesterone <8.75 ng/ml and received the rescue protocol, whereas no patients in the s.c. progesterone group received the rescue protocol. OPR, along with positive pregnancy and clinical pregnancy rates, were comparable between the s.c. progesterone group without the rescue protocol and the vaginal progesterone gel group with the rescue protocol. After the rescue protocol, the route of progesterone administration was not a significant predictor of ongoing pregnancy. The impact of different serum progesterone concentrations on reproductive outcomes was evaluated by percentile (<10th, 10-49th, 50-90th and >90th percentiles), taking the >90th percentile as the reference subgroup. In both the vaginal progesterone gel group and the s.c. progesterone group, all serum progesterone percentile subgroups had similar OPR. Subcutaneous progesterone 25 mg b.d. secures serum progesterone >8.75 ng/ml, whereas additional exogenous progesterone (rescue protocol) was needed in 15.8% of patients who received vaginal progesterone. The s.c. and vaginal progesterone routes, with the rescue protocol if needed, yield comparable OPR.

Systematic use of long-acting intramuscular progesterone in addition to oral dydrogesterone as luteal phase support for single fresh blastocyst transfer: A pilot study.

The need of luteal support after FET is no longer to be proven. Different routes of progesterone administration are available with interindividual differences in metabolization and serum progesterone levels, the latter being highly correlated with pregnancy and delivery rates. The administration of 2 different routes of progestogen significantly improves success rates in FET. The aim of the current study was to investigate the added value to combine intramuscular administration of progesterone to dydrogesterone in fresh embryo transfer. This is a retrospective study from prospectively collected data. Patient, aged between 18 and 43 years old, had received a fresh blastocyst transfer between January 2021 and June 2021. In the first group, all patients received only oral dydrogesterone 10mg, three times a day, beginning the evening of oocyte retrieval. In the second group, patients received, in addition to dydrogesterone, a weekly intramuscular injection of progesterone started the day of embryo transfer. Primary endpoint was ongoing pregnancy rate. 171 fresh single blastocyst transfers have been performed during this period. 82 patients were included in "dydrogesterone only" and 89 patients in "dydrogesterone + IM". Our two groups were comparable except for body mass index. After adjustment on BMI, our two groups were comparable regarding implantation rate, early pregnancy rate (46.1 versus 54.9, OR 1.44 [0.78; 2.67], p=0.25) miscarriage rate, ongoing pregnancy rate (30.3 versus 43.9, OR 1.85 [0.97; 3.53] p= 0.06). Using systematically long acting intramuscular progesterone injection in addition to oral dydrogesterone as luteal phase support seems to have no significant impact on IVF outcomes when a single fresh blastocyst transfer is performed.

P-690 Time to bust some myths about progesterone supplementation in the luteal phase. Role of the route of administration and usefulness (or uselessness) of plasma determination

Abstract Study question Is it worth measuring plasma progesterone levels after FET? Is there any difference in results depending on the route of progesterone administration? Summary answer The administration route of progesterone supplementation after FET entails different plasmatic levels (whose determination is useless) but without any correlation with ongoing pregnancy. What is known already Embryonic aneuploidy is likely to be the major contributor to human implantation failure, but not all failures are due to embryonic defects. The need for progesterone supplementation in ART frozen-thawed cycles is well accepted. Several studies have demonstrated an increase in live birth rate with progesterone luteal support although there is a discussion on the association of Progesterone levels on day of embryo transfer and birth or pregnancy loss rates. Moreover, although the effect of route of administration of progesterone on serum levels and pregnancy rates have been thoroughly studied, there is no consensus on the optimal endometrial preparation protocol. Study design, size, duration Prospective, randomized study performed during the 2020-21. A total of 201 genetically screened blastocyst (after PGT-A) transfers were performed after endometrial preparation, performed with exogenous estrogen administration followed by progesterone administration before embryo transfer (ET) . After embryo transfer, two different Progesterone regimens were randomly administered. Group I and Group II (see “Participants”) Participants/materials, setting, methods Group I patients (n = 100): 800 mg of micronized Progesterone was administered vaginally (Cyclogest® 1-0-1). Group II patients (n = 101): vaginal administration of 400 mg of micronized progesterone was combined with the subcutaneous administration of 25 mg of Progesterone (Prolutex 25®) Plasmatic progesterone (PP) levels on day of B-HCG determination (pregnancy test) (10 days after ET) and ultrasound confirmation of pregnancy (3 weeks after ET) were determined. The relationship between progesterone levels and ongoing pregnancy rates was amalyzed. Main results and the role of chance The rate of positive pregnancy test among the 201 FET was 71,64%. The overall ongoing pregnancy was 58,71%. PP on day of pregnancy test was 24,92±1,27 ng/ml (mean±SEM). The corresponding figures por positive (n = 144) and negative (n = 57) HCG were 27,65±1,09 and 20,33±2,13 respectively (t = 2,68; p = 0,008). The PP levels on day of HCG determination were 23,12±1,48 among ongoing pregnancies whereas the levels among non-evolutive gestations were 48,78±3,55 (t = 7,19; p = 0,000). PP levels were significantly higher among group II patients (combined treatment) both, on day of B-HCG determination (28,25±1,22 ng/ml) and on day of ultrasound confirmation of a gestational sac (33,61±2,39) than among group I patients (vaginal treatment) (15,12±1,60 and 19,77±1,50 ng/ml) (t = 0651, p = 0,000 and t = 5,38, p = 0,000 respectively). But these differences do not correlate with ongoing pregnancy rates: 59 out of 101 (58,42%) in group I patients and 59 out of 100 (59%) in group II patients. Limitations, reasons for caution Even though only euploid embryos have been transferred, ee must be cautious when drawing conclusions from the present study taking into account the limited number of cases evaluated. Wider implications of the findings Since only euploid embryos have been transferred in the present study, results in terms of successful ongoing pregnancies may be influenced by endometrial factors. Although the need of progesterone supplementation among frozen-thawed cycles is accepted, some debate exists on the route of administration and the need of progesterone serum determinations Trial registration number NOT applicable

Preparation of the Endometrium for Frozen Embryo Transfer: A Systematic Review.

Despite the worldwide increase in frozen embryo transfer, the search for the best protocol to prime endometrium continues. Well-designed trials comparing various frozen embryo transfer protocols in terms of live birth rates, maternal, obstetric and neonatal outcome are urgently required. Currently, low-quality evidence indicates that, natural cycle, either true natural cycle or modified natural cycle, is superior to hormone replacement treatment protocol. Regarding warmed blastocyst transfer and frozen embryo transfer timing, the evidence suggests the 6th day of progesterone start, LH surge+6 day and hCG+7 day in hormone replacement treatment, true natural cycle and modified natural cycle protocols, respectively. Time corrections, due to inter-personal differences in the window of implantation or day of vitrification (day 5 or 6), should be explored further. Recently available evidence clearly indicates that, in hormone replacement treatment and natural cycles, there might be marked inter-personal variation in serum progesterone levels with an impact on reproductive outcomes, despite the use of the same dose and route of progesterone administration. The place of progesterone rescue protocols in patients with low serum progesterone levels one day prior to warmed blastocyst transfer in hormone replacement treatment and natural cycles is likely to be intensively explored in near future.

Intramuscular progesterone optimizes live birth from programmed frozen embryo transfer: a randomized clinical trial

To determine whether vaginal progesterone for programmed endometrial preparation is noninferior to intramuscular progesterone in terms of live birth rates from frozen embryo transfer (FET). Three-armed, randomized, controlled noninferiority trial. Multicenter fertility clinic. A total of 1,346 volunteer subjects planning vitrified-warmed transfer of high-quality nonbiopsied blastocysts were screened, of whom 1,125 subjects were ultimately enrolled and randomly assigned to treatment. The subjects were randomly assigned to receive, in preparation for FET, 50 mg daily of intramuscular progesterone (control group), 200 mg twice daily of vaginal micronized progesterone plus 50 mg of intramuscular progesterone every third day (combination treatment), or 200 mg twice daily of vaginal micronized progesterone. The primary outcome was live birth rate per vitrified-warmed embryo transfer. The secondary outcomes were a positive serum human chorionic gonadotropin test 2 weeks after FET, biochemical pregnancy loss, clinical pregnancy, clinical pregnancy loss, total pregnancy loss, serum luteal progesterone concentration 2 weeks after FET, and patient's experience and attitudes regarding the route of progesterone administration, on the basis of a survey administered to the subjects between FET and pregnancy test. A total of 1,060 FETs were completed. The live birth rate was significantly lower in women receiving only vaginal progesterone (27%) than in women receiving intramuscular progesterone (44%) or combination treatment (46%). Fifty percent of pregnancies in women receiving only vaginal progesterone ended in miscarriage. The live birth rate after vaginal-only progesterone replacement was significantly reduced, due primarily to an increased rate of miscarriage. Vaginal progesterone supplemented with intramuscular progesterone every third day was noninferior to daily intramuscular progesterone, offering an effective alternative regimen with fewer injections. NCT02254577.

Subcutaneous progesterone versus vaginal progesterone for luteal-phase support in frozen-thawed embryo transfer: A cross-sectional study.

BackgroundLuteal-phase support is a complex and controversial issue in the field of reproductive management.Objective To compare the safety and efficacy of low-dose subcutaneous progesterone with the vaginal progesterone for luteal-phase support in patients undergoing rozen-thawed embryo transfer.Materials and MethodsIn this cross-sectional study, information related to 77 women that had frozen-thawed embryo transfer was reviewed. The patients were divided into two groups based on the route of progesterone administration used as a luteal-phase support. When the endometrial thickness reached 8 mm, in one group progesterone (Prolutex) 25 mg/ daily subcutaneous and in another group, vaginal progesterone (CyclogestⓇ) 400 mg twice or (EndometrinⓇ) 100 mg thrice daily, were administrated and continued until menstruation or in case of clinical pregnancy for 8 wk after the embryo transfer when the fetal heart activity was detected by ultrasonography.ResultsThe patient's characteristics were matched and there was no significant difference. The chemical and clinical pregnancy rate was higher in the vaginal progesterone group compared to the prolutex group, but statistically unnoticeable, (40% vs. 29.6%, p = 0.367) and (28% vs. 22.2%, p = 0.581), respectively.ConclusionThe findings of this study demonstrate that the new subcutaneous progesterone can be a good alternative for intramuscular progesterone in women that dislike and do not accept vaginal formulations as luteal-phase support in assisted reproductive technology.

Intramuscular progesterone versus 8% Crinone vaginal gel for luteal phase support following blastocyst cryopreserved single embryo transfer: a retrospective cohort study

BackgroundThe optimal route of progesterone administration for luteal support in cryopreserved embryo transfer (CET) has been the subject of much debate. While most published research has pertained to day 3 transfers, recent data on blastocyst CET has suggested that intramuscular progesterone (IMP) is superior to twice daily vaginal Endometrin suppositories for luteal phase support, resulting in significantly higher ongoing pregnancy rates. This study aimed to determine whether IMP is similarly superior to 8% Crinone vaginal gel for luteal phase support following blastocyst CET.MethodsAutologous and donor oocyte blastocyst cryopreserved single embryo transfer (SET) cycles from January 2014–January 2019 utilizing either 50 mg IMP daily or 90 mg 8% Crinone gel twice daily for luteal support were included. The primary outcome was live birth. Secondary outcomes included biochemical pregnancy, spontaneous abortion, and clinical pregnancy. All analyses were adjusted a priori for oocyte age. Log-binomial regression analysis was performed with differences in outcomes reported as relative risk (RR) with 95% confidence intervals (CI).ResultsA total of 1710 cycles were included, of which 1594 utilized IMP and 116 utilized 8% Crinone gel. Demographic and cycles characteristics were similar between the two groups. Compared to cycles utilizing IMP, cycles utilizing Crinone gel resulted in similar rates of live birth (RR 0.91; 95% CI 0.73–1.13), biochemical pregnancy (RR 1.12, 95% CI 0.65–1.92), spontaneous abortion (RR 1.41, 95% CI 0.90–2.20), and clinical pregnancy (RR 1.00, 95% CI 0.86–1.17).ConclusionsCompared to cryopreserved blastocyst SET cycles utilizing IMP for luteal support, cycles utilizing 8% Crinone gel resulted in similar likelihood of live birth.

In vitro fertilization and psychological stress: new insight about different routes of progesterone administration

In vitro fertilization and psychological stress: new insight about different routes of progesterone administration

Predictive factors of gestational diabetes in pregnancies following assisted reproductive technology: a nested case-control study.

To evaluate predictive factors for gestational diabetes mellitus (GDM) in singleton pregnancy following assisted reproductive technology (ART). This nested case-control study was performed during October 2016-June 2017. Pregnant women who conceived following ART procedures referred to infertility clinic were selected and categorized into GDM and non-GDM based on ADA/IAPDSG criteria. The study variables including age, educational status, first-degree family history of chronic diseases, systolic and diastolic blood pressure, previous obstetric and perinatal outcomes, infertility history, and ART cycle characteristics were collected from medical records. Prediction model to develop GDM was employed by binary logistic regression analysis after adjustment for age and body mass index, family history of diabetes, and gravidity. In total, 270 women with singleton pregnancies (consisted of 135 GDM and 135 non-GDM women) conceived were studied. According to the final model, significant predictors of GDM were history of polycystic ovarian syndrome (PCOS), previous ovarian hyper-stimulation syndrome (OHSS) risk and progesterone injections. Administration of injectable progesterone during the first 10-12weeks of pregnancy was associated with an approximately twofold increased risk of developing GDM [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.27-4.09)] compared to vaginal progesterone. In addition, the regression analysis revealed that previous OHSS risk (OR 2.40, 95% CI 1.34-4.31) and history of PCOS (OR 2.76, 95% CI 1.26-6.06) were other most important predictors of GDM. The route of progesterone administration, previous OHSS risk and history of PCOS seem to be putative risk factors for GDM in women conceived by ART.

Oral Versus Vaginal Progesterone In Preterm Labor

Background: Preterm labor (PTL) remains a distressing issue in modern obstetrics, and still associated with poor impact on the perinatal outcomes world-wide. Progesterone plays a vital role in preventing the PTL.Objective: To compare different route of progesterone administration on the perinatal outcomes.Patients and Methods: It was a prospective comparative clinical trial, conducted at Suez Canal University Hospitals, Ismailia from December 2015 to January 2017. One hundred and thirty eight pregnant patients were randomly selected at 20–24 weeks gestation´ at risk of PTL and were classified into: 72 women received oral dydrogesterone 10 mg twice a day [Duphastone®] (Oral group) and 66 women received vaginal progesterone 200 mg vaginally twice a day [Prontogest®] (vaginal group). The primary outcome measures were gestational age at delivery in weeks, birth weight in grams, Apgar score at 1 and 5 minutes, the need for neonatal intensive care unit admission and neonatal mortality.Results: There was a significant difference between both group in favor to the vaginal group in all the studied outcome measures (p value < 0.05) with the exception of the Apgar score at 5 minutes post delivery (p value = 0.1). No cases of perinatal mortality in the vaginal group and only 3 cases in the oral group.Conclusion: The vaginal route is of better and significant results.

A case of oral desensitization for hypersensitivity to exogenous progesterone

Hypersensitivity reaction to progesterone is a rare pathologic condition which consists of autoimmune response to endogenous progesterone, known as autoimmune progesterone dermatitis, and hypersensitivity reaction to exogenous progestogen. We report the case of a 31-year-old woman with a history of whole body urticaria during exogenous progesterone supplementation for in vi-tro fertilization (IVF). She was admitted to the hospital for the diagnosis and management of progestogen hypersensitivity. An intra-dermal test with progesterone revealed positivity to 5 mg/mL of progesterone. For her next IVF, progesterone desensitization was performed in a method combining oral and intramuscular progesterone administration. After successfully achieving a target dose of 100 mg per day, the route of progesterone administration was converted to intravaginal tablet (90 mg twice a day) without any hypersensitivity reactions. (Allergy Asthma Respir Dis 2017;5:294-297)

Progesterone Supplementation for Luteal Support: Efficacy and Patient Experiences With Vaginal Inserts (Endometrin®) Versus Intramuscular Injection

BACKGROUND: Progesterone is administered to counteract luteal phase defects that may occur during stimulated in vitro fertilization (IVF) cycles. Several routes of progesterone administration are available, although no single method is considered the standard of care. Comparative data are needed to establish a preferred mode of progesterone supplementation. OBJECTIVE(S): To evaluate the efficacy, tolerability, and patient experiences with luteal support using progesterone vaginal inserts (PVI; Endometrin ) vs intramuscular injection of progesterone in oil (PIO) for women undergoing IVF cycles. MATERIALS AND METHOD(S): Women (aged 18 to 42 years) with a documented history of infertility who were suitable candidates for IVF were enrolled in 1 of 2 multicenter, open-label, exploratory studies. The 2 study designs were similar, with the exception of gonadotropin-releasing hormone (GnRH) antagonist use in the first study and only women with polycystic ovary syndrome (PCOS) were included in the second study. Participating centers followed standard IVF protocols. Prior to ovarian stimulation with menotropins for injection (Menopur ) or follitropin beta injection (Follistim AQ ), women were randomized to luteal support with either PVI or PIO. Biochemical, clinical, and ongoing pregnancy (defined as a positive human chorionic gonadotropin serum pregnancy test, presence of a gestational sac, and fetal heart movements, respectively) was assessed. Patients’ experiences were evaluated through a questionnaire administered at the time of the first pregnancy test and at the final study visit. RESULT(S): The combined intent-to-treat population (all randomized patients who received at least 1 dose of study medication) included 137 women treated with PVI and 138 women treated with PIO. The mean number of embryos transferred was comparable between treatment groups for each study. Among women with GnRH antagonist IVF cycles, ongoing pregnancy rates were 44.0% and 46.9% in the PVI and PIO treatment groups, respectively. Similar findings were observed in the PCOS study, with ongoing pregnancy rates of 47.2% (PVI) and 49.1% (PIO). Women who were treated with PVI reported greater administration convenience, ease of use, and overall satisfaction than did womenwho received PIO. Studymedications were generally well tolerated; the majority of adverse events that occurred during the luteal support phase were mild to moderate in intensity. CONCLUSION(S): Luteal support via PVI is as effective as PIO yet provides greater convenience and ease of use. Progesterone vaginal inserts are a patient-friendly alternative to PIO for women undergoing IVF cycles. FINANCIAL SUPPORT: This study was supported by Ferring Pharmaceuticals, Inc.

The Use of Progesterone in Clinical Practice: Evaluation of its Efficacy in Diverse Indications Using Different Routes of Administration

Introduction: Progesterone is a hormone of paramount importance in the reproductive physiology. Its multiple physiological roles and pharmacology have been extensively studied throughout the years. However, the use of progesterone in the pathophysiology of pregnancy as well as in its other indications remains arguable for diverse reasons. One of these reasons concerns the fact that there have been few large randomised controlled trials, which are not easily comparable because of the different dosages, populations and routes of administration used. Regarding this last issue, the route of progesterone administration may have a strong influence on the efficacy of the treatment since the distribution and concentration of the hormone at the tissutal level varies considerably. Objective: To review the literature concerning the efficacy of progesterone in its diverse indications in correlation to the different routes of administration used. Methods: The search strategy included a literature search of PubMed, MEDLINE and the Cochrane Database from 1949 to April 2005, as well as a review of reference lists of identified studies and a hand search of relevant textbooks and reference works. Search terms used included: progesterone, pregnancy, preterm birth, preterm labor, threatened miscarriage, recurrent miscarriage, menopause, contraception, pharmacology, route of administration. Study designs included experimental studies, observational studies, case control studies, reviews, letters, and editorials. Results: The search on MEDLINE identified approximately 3800 articles. We found only limited literature relating to some of the administration route of progesterone (transnasal, transdermic, sublingual, rectal). Conclusion: Many routes of progesterone administration have been studied, but the only routes of administration used in the clinical practice are the i.m., oral and vaginal one. Among these options, the intramuscular administration is the only one that ensures adequate and verifiable plasmatic levels of progesterone.

Different routes of progesterone administration and polycystic ovary syndrome: A review of the literature

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in woman of reproductive age. Although extensive studies have been performed in past decades to investigate the pathobiological mechanisms underlying the unset of this disease, its etiology remains unknown. Progesterone is a hormone of paramount importance in ovulation, implantation and luteal phase support. Low levels of progesterone have been found in the early luteal phase in PCOS patients. Granulosa cells from polycystic ovaries show an altered progesterone production. Moreover, the lack of cyclical exposure to progesterone may have a role in the development of the gonadotropin and androgen abnormalities found in PCOS patients. Ovulation failure and progesterone deficiency may facilitate the hypothalamic–pituitary abnormalities causing the associated disordered luteinizing hormone secretion in PCOS. Progesterone may be administered to PCOS patients in the following cases: to induce withdrawal bleeding, to suppress secretion of luteinizing hormone, in ovulation induction in clomiphene citrate-resistant patients and in luteal phase support in assisted reproduction. We discuss the pharmacologic characteristics of the different routes of progesterone administration with reference to these diverse indications, the therapeutic objectives and patient compliance.

Luteal phase support in assisted reproductive technology

The purpose of this review is to discuss luteal support in assisted reproduction and to provide an evidence-based overview of the current options available. The luteal phase has been found to be defective in virtually all of the stimulation protocols used for in-vitro fertilization. Common mechanisms such as supraphysiological levels of estradiol, decreased output of luteinizing hormone, inhibition of the corpus luteum and asynchronization of estradiol and progesterone may be involved in insufficient function of the corpus luteum in assisted reproductive technology. Gonadotropin releasing hormone agonist undoubtedly provides benefits in stimulated cycles, however it also has adverse effects, inhibition of the corpus luteum together with supraphysiological hormonal profiles finally leading to luteal phase defects. Luteal phase support with human chorionic gonadotropin or progesterone after assisted reproduction results in increased pregnancy rates. The role of luteal phase support in these cycles has also been recently elucidated. Use of human chorionic gonadotropin for luteal phase support is associated with a marked increase in the risk of ovarian hyperstimulation syndrome, therefore progesterone is the preferred choice. Data on the benefits of estrogen supplementation are conflicting. Among the routes of progesterone administration, reductions in pregnancy rates are noted on oral administration. In spite of a lack of statistical significance, the intramuscular route seems to be more beneficial than the vaginal route when considering rates of ongoing pregnancy and live birth. Further clarification is needed on the ideal dose, the optimal route and the duration of progesterone administration in assisted reproduction.