Support In IVF Research Articles

Egyptian Foundation of Reproductive Medicine and Embryology Survey for Luteal Support in IVF among Fertility Specialists

Egyptian Foundation of Reproductive Medicine and Embryology Survey for Luteal Support in IVF among Fertility Specialists

P-555 Do IVF patients prefer the rectal route to the vaginal for luteal phase progesterone administration? - a cohort study

Abstract Study question How do IVF patients perceive rectal administration of progesterone for luteal phase support compared to vaginally administered progesterone? Summary answer Rectal administration of progesterone causes less discomfort in IVF patients, undergoing Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) and is preferred compared to vaginal administration. What is known already Progesterone is essential for implantation and normal development of pregnancy in spontaneous pregnancies as well as in ART pregnancies. In IVF, progesterone is most often administered vaginally in Europe for luteal phase support, although, this route may cause cumbersome discharge, vaginal bleeding, and irritation of the vulva. For many years the vaginal route has been the gold standard, although, progesterone is well absorbed rectally and recent studies have shown that rectally administered micronized progesterone was well accepted among IVF patients. Until now, in IVF very little focus has been on patient convenience as regards luteal phase support. Study design, size, duration An interventional cohort study, conducted from January 2020 to November 2022 in a public fertility clinic. A total of 479 patients received a questionnaire (Q1) by e-mail during the period between the embryo transfer and the pregnancy test; A second questionnaire (Q2) was answered at the time of the first ultrasound scan in gestational week 7. Participants/materials, setting, methods Patients underwent an HRT-FET protocol, including vaginal progesterone (VP) (400mg/12hours). In patients with serum progesterone levels lower than 11 ng/ml on the 6th day of progesterone, additional progesterone was administered rectally (RP) (400mg/12hours) from that day until the day of pregnancy testing, and in pregnant patients until the first scan in week 7. Side effects and patient convenience of both routes were reported in a questionnaire, including 27 questions, using a visual analog scale (0-100). Main results and the role of chance A total of 73% of HRT-FET patients (349/479) answered Q1 before the pregnancy test and a total of 27 % (93/349) of the cohort received progesterone both vaginally and rectally. The response rate of Q2 in gestational week 7 was 100 % (221/221) and a total of 28 % of patients (62/221) administered progesterone both vaginally and rectally. In Q1, a total of 60% of patients (54/90) preferred RP over VP in the cohort of patients treated with both administration regimens. In Q2, a total of 62% of patients (37/60) preferred RP over VP in the cohort of patients treated with both administration regimens. The overall discomfort was lower in relation to RP in both questionnaires and, especially discharge was lower in RP compared to VP; median interquartile range (IQR) in Q1: 11 (3-23) vs. 50 (25-66) and Q2: 19 (9-28) vs. 47 (22-62), respectively. Changes in defecation pattern after RP were reported in Q1 as well as Q2, 48% (45/92) and 55% (34/61), however, the discomfort was reported as mild. An increased flatulence was reported by 50% (46/92) in Q1 and 63% (39/92) in Q2, however, again the discomfort was reported as mild. Limitations, reasons for caution Currently, it is unknown whether the present results apply to progesterone products other than the one used in the present study (Cyclogest®). The questionnaire used, although having been used in another published study with another progesterone product, was not specifically validated for this product. Wider implications of the findings The rectal route should be remembered for luteal phase support in IVF, and some patients might choose the rectal route over the vaginal for their luteal phase support due to less discharge. Trial registration number EudraCT no.: 2019-001539-29

IVF and the exogenous progesterone-free luteal phase.

In a conventional IVF cycle, final oocyte maturation and ovulation is triggered with a bolus of hCG, followed by progesterone-based luteal support that spans several weeks if pregnancy is achieved. This article summarizes several approaches of the exogenous progesterone-free luteal support in IVF. Triggering ovulation with GnRH agonist may serve as an alternative to hCG, with well established advantages. In addition, the luteal phase can be individualized in order to achieve a more physiologic hormonal milieu, and a more patient friendly treatment, alleviating the burden of a lengthy exogenous progesterone therapy. GnRH agonist trigger followed by a 'freeze all' policy is undoubtedly the best approach towards the 'OHSS-free clinic'. If fresh embryo transfer is considered well tolerated after GnRH agonist trigger, rescue of the corpora lutea by LH activity supplementation is mandatory. Herein we discuss the different approaches of corpus luteum rescue.

Does Supporting the Luteal Phase With Progesterone Only Without Estradiol Can Affect the Pregnancy Outcome in In-Vitro Fertilization Cycles?

AbstractBackground: It is well established that luteal support with progesterone improves implantation in IVF cycles. Unfortu-nately, there are conflicting reports regarding the value of luteal phase estradiol supplementation on pregnancy rates.Aim of Study: To compare the pregnancy rate if we use progesterone only versus the use of progesterone and estradiol as a luteal phase support in IVF cycles.Study Design and Setting: A prospective randomized clinical trial.Patients and Methods: This study has been carried out in Tanta University Hospital in co-ordination with private IVF centers in the period from October 2017-to June 2018.This study included 60 women divided into two group:•Group I consists of 30 patients who received vaginal admin-istration of progesterone supplementation in the form of 400mg prontogest twice a day.•The second group consists of 30 patient in which 2mg estradiol valerate twice daily with prontogest suppositories has been used.Results: The findings suggest that the pregnancy rate is higher with the estrogen and progesterone supplementation than the progesterone only supplementation in both groups who have used GnRH agonist or antagonist controlled ovarian stimulation protocol but it has not reached a statistically significant value.Conclution: Supplementary administration of E2 to p for luteal phase support may be beneficial for better IVF outcome and it warrants further investigation.

A Phase III randomized controlled trial of oral dydrogesterone versus intravaginal progesterone gel for luteal phase support in in vitro fertilization (Lotus II): results from the Chinese mainland subpopulation

Lotus II, a randomized, open-label, multicenter, international study compared the efficacy and safety of oral dydrogesterone versus micronized vaginal progesterone (MVP) gel for luteal support in IVF. A prespecified subgroup analysis was performed on 239 Chinese mainland subjects from the overall study population (n = 1034), who were randomized to oral dydrogesterone 30 mg or 8% MVP gel 90 mg daily from the day of oocyte retrieval until 12 weeks of gestation. The aim was to demonstrate non-inferiority of oral dydrogesterone to MVP gel, assessed by the presence of a fetal heartbeat at 12 weeks of gestation. In the Chinese mainland subpopulation, there was a numerical difference of 9.4% in favor of oral dydrogesterone, with ongoing pregnancy rates at 12 weeks of gestation of 61.4% and 51.9% in the oral dydrogesterone and MVP gel groups, respectively (adjusted difference, 9.4%; 95% CI: −3.4 to 22.1); in the overall population, these were 38.7% and 35%, respectively (adjusted difference, 3.7%; 95% CI: −2.3 to 9.7). In both the Chinese mainland subpopulation and the overall population, dydrogesterone had similar efficacy and safety to MVP gel. With convenient oral administration, dydrogesterone has potential to transform luteal support treatment.

Subcutaneous Progesterone Is Effective and Safe for Luteal Phase Support in IVF: An Individual Patient Data Meta-Analysis of the Phase III Trials.

ObjectiveTo summarize efficacy and safety data on a new progesterone compound which is available for subcutaneous administration as compared to vaginally administered progesterone for luteal phase support in patients undergoing IVF treatment.DesignData from two randomized phase III trials (07EU/Prg06 and 07USA/Prg05) performed according to GCP standards with a total sample size of 1435 per-protocol patients were meta-analyzed on an individual patient data level.SettingUniversity affiliated reproductive medicine unit.PatientsSubcutaneous progesterone was administered to a total of 714 subjects and vaginal progesterone was administered to a total of 721 subjects who underwent fresh embryo transfer after ovarian stimulation followed by IVF or ICSI. The subjects were between 18 and 42 years old and had a BMI <30kg/m2.InterventionsSubcutaneous progesterone 25 mg daily vs. either progesterone vaginal gel 90 mg daily (07EU/Prg06) or 100 mg intravaginal twice a day (07USA/Prg05) for luteal phase support in IVF patients.Main outcome measuresOngoing pregnancy rate beyond 10 gestational weeks, live birth rate and OHSS risk.ResultsThe administration of subcutaneous progesterone versus intra-vaginal progesterone had no impact on ongoing pregnancy likelihood (OR = 0.865, 95% CI 0.694 to 1.077; P = n.s.), live birth likelihood (OR = 0.889, 95% CI 0.714 to 1.106; P = n.s.) or OHSS risk (OR = 0.995, 95% CI 0.565 to 1.754; P = n.s.) in regression analyses accounting for clustering of patients within trials, while adjusting for important confounders. Only female age and number of oocytes retrieved were significant predictors of live birth likelihood and OHSS risk.ConclusionNo statistical significant or clinical significant differences exist between subcutaneous and vaginal progesterone for luteal phase support.

Starting time of progesterone luteal phase support in IVF: a systematic review and meta-analysis

Starting time of progesterone luteal phase support in IVF: a systematic review and meta-analysis

Progesterone vaginal ring versus vaginal gel for luteal support with in vitro fertilization: a randomized comparative study

To compare the efficacy and safety of luteal phase support in IVF with a progesterone (P) vaginal ring or gel (VR or VG). Prospective, randomized, single-blind, multicenter, phase III clinical trial (ClinicalTrials.gov identifier: NCT00615251). Nineteen private and three academic high-volume U.S. IVF centers. One thousand two hundred ninety-seven infertile patients were randomized to a weekly P VR (n = 646) or a daily P 8% VG (n = 651). IVF was performed per site-specific protocols. The day after egg retrieval, patients were randomized and began VR or VG therapy, which continued for up to 10 weeks' gestation. Clinical pregnancy rates at 8 and 12 weeks of pregnancy; rates of biochemical pregnancy, live birth, spontaneous abortion, ectopic pregnancy, and cycle cancellation; and safety and tolerability were secondary measures. Clinical pregnancy rates at 8 and 12 weeks were high and comparable between groups: 48.0% for VR and 47.2% for VG at week 8 and 46.4% (VR) and 45.2% (VG) at week 12. Live-birth rates were 45% (VR) and 43% (VG). Adverse event profiles were similar between groups. The weekly P VR provided similar pregnancy rates to the daily VG, with no major differences in safety.

Progesterone support in IVF: is evidence-based medicine translated to clinical practice? A worldwide web-based survey

This worldwide web-based survey compared the clinical practice for luteal-phase supplementation (LPS) in stimulated IVF cycles to the current evidence-based literature. Eighty-four treatment centres in 35 countries, representing a total of 51,155 IVF cycles/year, responded. Vaginal progesterone alone was used for LPS in 64% of cycles and in another 16% of cycles in combination with either i.m. (15%) or oral progesterone (1%). As a single agent, i.m. progesterone was used in 13% of cycles, oral progesterone in another 2% and human chorionic gonadotrophin (HCG) was still used in 5% of cycles. Progesterone was administered until 10–12weeks’ gestation in 67% of cycles and in 22% and 12% it was discontinued when fetal heart pulsations are recognized or until βHCG was positive, respectively. In conclusion, in almost two-thirds of the assisted cycles represented in this survey, vaginal administration of progesterone is preferred for LPS. Nevertheless, despite the available literature on the disadvantages of oral progesterone, i.m. progesterone and HCG for LPS, these agents are still used routinely by many practitioners. Furthermore, although there is no firm evidence to support the continuation of LPS until 10–12weeks’ gestation, this practice is used in the majority of IVF cycles worldwide.This worldwide web-based survey assessed the clinical practice for luteal-phase support in stimulated cycles in comparison to the current evidence-based literature. The survey included the following questions: (i) ‘What is the progesterone you use for luteal support?’; and (ii) ‘How long does progesterone needs to be administered in an IVF cycle if the patient becomes pregnant?’. Eighty-four units from 35 countries representing a total of 51,155 treated IVF cycles/year were included. Vaginal progesterone alone was used for luteal-phase supplementation in 64% of cycles. In another 16% of cycles, vaginal progesterone was used in combination with either intramuscular (15%) or oral progesterone (1%). As a single agent, intramuscular progesterone was used in 13% of cycles, oral progesterone in another 2%, and human chorionic gonadotrophin (HCG) was still used in 5% of cycles. Progesterone was administered until 10–12weeks’ gestation in 67% of cycles, in 22% of cycles it was discontinued when fetal heart pulsations are recognized, and in 12% it was administered until a positive pregnancy test. In conclusion, in agreement with the currently available literature, in almost two-thirds of assisted cycles worldwide, the vaginal route of progesterone administration is preferred for luteal-phase supplementation. Nevertheless, despite the described disadvantages of oral progesterone, intramuscular progesterone and HCG for LPS, these agents are still used routinely in clinical practice by many practitioners. Furthermore, although there is no firm evidence to support the continuation of LPS until 10–12weeks of gestation, this practice is used in the majority of IVF cycles worldwide.

Progesterone vaginal gel vs. intramuscular progesterone in oil for luteal support in IVF: a large, prospective trial

OBJECTIVE: To compare the efficacy of vaginal progesterone gel and intramuscular (IM) progesterone in oil for luteal phase support in IVF cycles. DESIGN: Prospective trial in a large private practice. MATERIALS AND METHODS: All patients were treated with either an oral contraceptive/leuprolide acetate down regulation protocol or a microdose flare protocol, depending on clinical indications. Ovarian stimulation was accomplished with recombinant FSH alone in the down regulated protocol; recombinant LH was added in the flare protocol. All patients received recombinant hCG at oocyte maturity, followed by transvaginal oocyte retrieval 36 hours later. Patients were prospectively assigned to either vaginal (Crinone® 8% vaginal gel) or IM progesterone in oil, beginning 2 days after the oocyte retrieval. Embryos were transferred either 3 or 5 days following retrieval based on the number and quality of embryos on Day 3. A serum hCG was obtained 14 days after oocyte retrieval and repeated weekly if positive until transvaginal sonography was performed at 7 weeks' gestational age to confirm cardiac motion in an intrauterine gestation. RESULTS: 511 consecutive patients were enrolled in the study; 474 completed participation. 37 were excluded for no autologous embryo transfer (freeze all, donor recipients, failed fertilization/cleavage). There were no demographic differences between the 2 treatment groups. Overall, patients who received vaginal progesterone gel had higher pregnancy (70.9% vs. 64.2%) and delivery (51.7% vs. 45.4%) rates than did patients who received IM progesterone. Patients 35 & under who received vaginal progesterone gel had significantly higher delivery rates (65.7% vs. 51.1%, p<0.05) than did patients who received IM progesterone. There were no differences, regardless of age, in the rates of biochemical pregnancy, miscarriage, or ectopic pregnancy. CONCLUSION: Luteal phase support with vaginal progesterone gel produced significantly higher pregnancy rates than IM progesterone in younger patients undergoing IVF.

Crinone vaginal gel is equally effective and better tolerated than intramuscular progesterone for luteal phase support in in vitro fertilization–embryo transfer cycles: a prospective randomized study

To compare the efficacy of Crinone vaginal gel and intramuscular progesterone (IMP) for luteal phase support in in vitro fertilization-embryo transfer (IVF-ET) with respect to pregnancy rates and outcomes, and to assess patient satisfaction with both products. Prospective randomized trial. University-affiliated IVF unit. Women under age 40 years with day-3 follicle-stimulating hormone levels <15 mIU/mL undergoing their first, second, or third IVF cycles on gonadotropin releasing-hormone (GnRH) down-regulation protocols. Luteal phase supplementation with either Crinone vaginal gel or IMP; phone survey regarding patient satisfaction with Crinone vaginal gel and IMP. Pregnancy rates, ongoing/delivered, failed pregnancy rates, and product satisfaction scores for patients supplemented with Crinone vaginal gel and with IMP. Four hundred sixty-eight patients were randomized, and 407 completed the study. The patients were randomized on the day of oocyte retrieval to receive either Crinone vaginal gel or IMP for luteal phase support. Pregnancy, ongoing/delivered, and failed pregnancy rates were similar between the Crinone and IMP treatment arms (OR [95% CI]: 1.2 [0.8, 1.8], 1.1 [0.8, 1.7], 1.0 [0.6, 1.7], respectively). On a scale of 1 to 5, patient satisfaction scores were statistically significantly higher with Crinone vaginal gel than with IMP (4.4 ± 0.9 vs. 2.8 ± 1.2). Crinone vaginal gel and IMP are equally effective for luteal phase support in IVF, but Crinone is better tolerated by patients.

Vaginal gel versus intramuscular progesterone for luteal phase supplementation: a prospective randomized trial

The aim of this randomized study was to compare the efficacy of intramuscular progesterone (IMP) and progesterone in vaginal gel (VGP) at two different doses for luteal support in IVF. A total of 412 patients, aged between 28 and 37 years, were randomized into three groups. The day after oocyte retrieval each patient began supplementation with one of the following: IMP 50 mg daily (150 patients), VGP 90 mg once daily (143 patients), or VPG 90 mg twice daily (148 patients). No significant difference was found between the three groups in any of the endpoints. The rate of positive β-human chorionic gonadotrophin per transfer was 38.4% with IMP, 35.0% with VPG once daily and 43.1% with VPG twice daily. Clinical pregnancy rate per transfer and implantation rate were 32.6% and 19.6% with IMP, 26.3% and 16.4% with one dose of VGP, and 37.2% and 21.1% with two doses of VGP. Live birth rate per transfer was 26.1%, 23.4% and 29.9%, respectively. Progesterone vaginal gel can be successfully used as an alternative to intramuscular progesterone for luteal support in IVF. One daily dose appears sufficient to induce clinical pregnancies and live births at a rate comparable to intramuscular supplementation.

GnRH agonist for luteal support in IVF? Setting the balance between enthusiasm and caution

GnRH agonist for luteal support in IVF? Setting the balance between enthusiasm and caution

AC-017 Comparison of the clinical outcome of crinone 8% administered vaginally or intramuscular plus oral progesterone for luteal support in IVF–embryo transfer cycles

AC-017 Comparison of the clinical outcome of crinone 8% administered vaginally or intramuscular plus oral progesterone for luteal support in IVF–embryo transfer cycles

Luteal support with vaginal micronized progesterone gel in assisted reproduction

The purpose of this study was to review the rationale for vaginal progesterone treatment as luteal support in IVF, and the clinical experience with vaginal micronized progesterone gel. It was found that luteal support with exogenous progesterone significantly improves implantation and pregnancy rates after IVF. Vaginal administration offers a number of potential advantages over intramuscular injection in terms of tolerability and convenience. The clinical experience with Crinone 8%, a vaginal gel containing 90 mg micronized progesterone in a polycarbophil base, indicates that the use of this preparation is associated with pregnancy rates comparable with those achieved after intramuscular administration of progesterone. Moreover, in studies in which patient preferences have been assessed, significantly higher preferences for vaginal micronized progesterone gel have been reported, compared with intramuscular administration or vaginal suppositories. In conclusion, the vaginal micronized progesterone gel used in this study provided effective and well-tolerated luteal support in women undergoing IVF.

Analysis of the bleeding pattern in assisted reproduction cycles with luteal phase supplementation using vaginal micronized progesterone

This study was designed to determine the effects of a vaginal micronized progesterone preparation on bleeding patterns and pregnancy outcomes after in-vitro fertilization and intracytoplasmic sperm injection (IVF-ICSI). The study population consisted of 149 consecutive women who had undergone IVF-ICSI using 'long-protocol' stimulation with buserelin-human menopausal gonadotrophin (HMG). A retrospective chart analysis of computerized medical records was undertaken. Vaginal progesterone (200 mg three times daily) was begun the day before oocyte retrieval and continued for a minimum of 16-19 days following human chorionic gonadotrophin (HCG) administration. Occurrence of bleeding following HCG injection, pregnancy rate and outcomes, and serum concentrations of oestradiol were measured. Women undergoing IVF and embryo transfer with ICSI and using vaginal progesterone for luteal support had normal luteal phase lengths (day of HCG minus day of onset of bleeding). In the absence of pregnancy, bleeding occurred after 19.2 +/- 3.9 days (mean +/- SD). Out of the pregnant group only three women bled within 19 days of HCG administration: two had biochemical pregnancies which spontaneously vanished and one evolved to term. The results reflect the normal bleeding pattern to be expected when vaginal progesterone is used for luteal support in IVF and embryo transfer, an approach whose efficacy has been amply proven. No shortened luteal phases were observed using vaginally administered progesterone.

The role of luteal phase support in infertility treatment: a meta-analysis of randomized trials

To determine whether the use of luteal phase support improves pregnancy rate (PR) in infertility. A meta-analysis of randomized trials of luteal phase support. Search of the National Library of Medicine MEDLINE data base from 1971 using the words luteal, pregnancy, human, and comparative. Bibliography of relevant articles, reviews, and abstracts of scientific meetings were hand searched. All randomized controlled trials of luteal phase support in infertility were included. Luteal phase support for recurrent abortion and nonrandomized trials were excluded. The common odds ratio was calculated for each intervention using the Mantel-Haentzel test. Homogeneity of treatment effect was evaluated using the Breslow-Day test. Pregnancy per cycle, rate of spontaneous abortion, and ovarian hyperstimulation syndrome rate. Eighteen trials met the above criteria. Human chorionic gonadotropin improved PRs in IVF when GnRH agonist (GnRH-a) was used (n = 151) and was superior to P (n = 352). Its benefit in all IVF cycles, however, was not established because of significant heterogeneity of treatment effect. Progesterone improved the PR in all IVF cycles (n = 457). No significant reduction in spontaneous abortion was noted with luteal support (n = 200). Ovarian hyperstimulation syndrome occurred in 5% of patients with hCG. Combination of data from trials of luteal support with other infertility therapies was not possible because of the differences in patient populations. The meta-analysis supports the routine use of hCG in IVF cycles using a GnRH-a. Progesterone was also beneficial for luteal phase support in IVF. For other infertility therapy, however, further research is needed to evaluate the role of luteal phase support.