scholarly journals THE EFFECT OF ADDITIONAL PROGESTERONE INJECTIONS ON CLINICAL OUTCOMES AFTER A LOW SERUM PROGESTERONE ON THE DAY OF EMBRYO TRANSFER

2021 ◽  
Vol 116 (3) ◽  
pp. e230-e231
Author(s):  
Jemma Garratt ◽  
Mona Rahmati ◽  
Elena Linara-Demakakou ◽  
Kamal Ahuja ◽  
Nick Macklon
2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Herencia ◽  
J Llácer ◽  
J A Ortiz ◽  
J C Castillo ◽  
C Gavilán ◽  
...  

Abstract Study question Can we rescue treatments with low progesterone (PG) levels the day of frozen embryo transfer (FET) by adding subcutaneous progesterone? Summary answer After receiving additional supplementation with subcutaneous progesterone, women with low serum progesterone on cryotransfer day, have similar ongoing pregnancy rates as women with normal levels. What is known already Micronized vaginal progesterone fails to achieve optimal serum levels in up to 30% of patients receiving frozen embryos under artificial cycles (AC) despite the administration of 400 mg twice daily. Cancelling the thawing process and restarting a new treatment is a very disappointing option for patients and doctors. An alternative strategy is to administrate additional progesterone subcutaneously. The efficacy of the additional administration of subcutaneous progesterone as a “rescue” strategy in terms of clinical outcomes remains to be validated. Study design, size, duration We included 356 FET performed at Instituto Bernabeu between January 2019 - August 2020 in a retrospective case-control study. Groups were established according to PG levels on the day of the embryo transfer. The Control Group included: patients with optimal progesterone levels (≥8.8 ng ml); while the Rescue Group included those with suboptimal progesterone levels (<8.8 ng ml). Participants/materials, setting, methods All patients performed frozen embryo transfer after artificial endometrial preparation. All embryo transfers were performed at blastocyst stage after 5 days of progesterone administration. Progesterone levels were assessed the day of the embryo transfer by an electrochemiluminescence immunoassay. Samples were obtained 2–5 hours after the last vaginal progesterone administration. Primary outcome was Ongoing Pregnancy Rates (OPR). Secondary outcomes were pregnancy rates (PR), miscarriage rates (MR) and biochemical miscarriage (BM). Main results and the role of chance 301 patients were included in the Control Group and 55 in the Rescue Group. No significant differences were found between both groups. OPR rate was 34.7% for patients in the control group versus 26.4% in the rescue group (p = 0.240) PR was 52.5% for patients with optimal PG levels vs 54.5% when PG levels were below 8.8 ng/mL. Both BM and MR tend to be higher in women who had low serum PG: BM (21.4% vs 15.5%) and MR (28.6% vs 18.1%), without reaching significant statistical difference. In addition, we analyzed data from a sub-group of patients who received extra subcutaneous progesterone (based on cliniciańs decision), despite having normal serum PG levels. No differences in clinical outcomes between these groups were observed either. OPR was 29%, vs 35.4% (p = 0.241), PR was 51.8% vs 53.7%; BM was 16.7% vs 16.3% and MR was 26.9% vs 17.1% between women who received an extra subcutaneous PG dose versus women who did not, respectively. Weight and BMI distribution were homogeneous across groups. A discreet difference was observed in age distribution (control group mean age 41.6 years vs. 39.7 years in the rescue group). Limitations, reasons for caution The retrospective collection of data and a limited sample size constitutes the main limitations of the study. Significant statistical differences were not found between groups but still differences might be clinically relevant. Larger studies are needed to reach robust conclusions on the strategy. Wider implications of the findings: In AC cycles, when supplemented with additional subcutaneous progesterone, women showing low serum progesterone on cryotransfer day may expect similar clinical outcomes as women with normal levels. Pending on confirmatory studies, this strategy could consider as an alternative to cycle cancellation. Trial registration number Not applicable


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F K Boynukalin ◽  
R Abalı ◽  
M Gultomruk ◽  
B Demir ◽  
Z Yarkiner ◽  
...  

Abstract Study question Does SC-P provide similar ongoing pregnancy rates (OPRs) as intramuscular progesterone(IM-P) in hormone replacement therapy (HRT)-FET cycles and do serum progesterone (P) levels on FET day effect on pregnancy outcome? Summary answer: SC-P administration had similar OPR compared to IM-P in HRT-FET cycles. In SC-P group embryo transfer(ET) day P found to be insignificant factor for outcome. What is known already Different P routes can be used in HRT-FET cycles such as vaginal P, IM-P and recently SC-P. Only retrospective studies evaluated the comparison of SC-P with other routes in HRT-FET cycles. Here, we assessed prospectively whether SC-P is effective for HRT-FET cycles. Previous studies reported that serum P levels on ET day after vaginal P administration clinical outcomes were closely correlated. The correlation between serum P after IM-P administration and clinical outcomes were conflicting. In addition, there is lack of data on the serum P levels after SC-P administration. Serum P levels on ET day were evaluated in this study. Study design, size, duration This prospective cohort study was performed between July 1-October 31 2020, enrolled 224 patients scheduled for HRT-FET cycles with SC-P(25 mg twice daily) or IM-P(50 mg once daily). The route of P was decided according to the patient’s eligibility to hospital. First FET cycle was included after freeze-all cycles for each patients. Female age>35, PGT-A cycles, cleavage ET, >1 ET, patients with uterine pathology and hydrosalpinx, FET with surplus embryos, endometrial thickness<7mm were excluded. Participants/materials, setting, methods Female age ≤ 35 years old with a triple-layer endometrium >7 mm underwent transfer of single blastocysts after the first ET after freeze-all cycles. The indications for freeze-all were ovarian hyperstimuation syndrome and trigger day P level>1.5 ng/ml. 224 patients were eligible for study; 133 in SC-P group and 91 in IM-P group.The primary endpoint was the ongoing pregnancy rate (OPR) beyond pregnancy week 12. Main results and the role of chance The demographic, cycle, embryologic characteristics were similar between groups. The median circulating P levels on the day of ET were 19.92(15.195–27.255)ng/
ml and 21(16.48–28)ng/ml in the SC-P and IM-P groups,(p = 0.786). The clinical pregnancy rates [86/133(64.7%) vs 57/91(62.6%);p=0.757], miscarriage rates [21/86(24.4%) vs 10/57(17.5%) ;p=0.329], and OPR [65/133 (48.9%) vs 47/91(51.6%); p = 0.683] were comparable between the SC-P and IM-P. Binary logistic regression was performed for ongoing pregnancy as the dependent factor blastocyst morphology was found to be the only significant independent prognostic factor (p = 0.006), whereas the route of P was insignificant. In the SC-P and IM-P 
groups, the effect of ET day P levels were divided into quartiles(Q) to evaluate the effect on ongoing pregnancy. In SC-P group OPR were similar in four Q [Q1:33.3%(11/33),Q2:50%(17/34),Q3:60.6%(20/33),Q4:51.5%(17/33) (p = 0.1)].For IM-P group; Q1 had a significantly reduced OPR than Q2, Q3, Q4. [26.1%(6/23),65.2%(15/23),54.5%(12/22) and 60.9%(14/23), p = 0.031]. Logistic regression analysis for OP was performed separately in SC-P group and IM-P group. Although in SC-P group, ET day P levels was not found to be a significant factor, in IM-P ET day P level was found to be an independent factor for OP in IM-P group (Q1vs Q2+Q3+Q4; OR: 8,178 95% CI: [1.387–48.223] p:0.02). . Limitations, reasons for caution Although this study has the advantage of being prospective and in a homogenous study population, randomized controlled trials are warranted to evaluate the effectiveness of SC-P to other routes of P. Extrapolation to unselected populations of this study is needed. Wider implications of the findings: Assignment of threshold of serum P on the day of ET for HRT-FET cycles to optimize outcomes is critical for every route of P. Regarding these results, individual luteal phase for HRT-FET cycles can improve IVF outcome. Trial registration number None


Author(s):  
José Metello ◽  
Claudia Tomás ◽  
Pedro Ferreira ◽  
Iris Bravo ◽  
MaryJo Branquinho ◽  
...  

Abstract Objective To establish a relationship between serum progesterone values on the day of frozen blastocyst transfer in hormone-replaced cycles with the probability of pregnancy, miscarriage or delivery. Methods This was an ambispective observational study including all frozen-thawed embryo transfer cycles performed at our department following in vitro fecundation from May 2018 to June 2019. The outcomes evaluated were β human chorionic gonadotropin (β-hCG)-positive pregnancy and delivery. Groups were compared according to the level of serum progesterone on the day of embryo transfer: the 1st quartile of progesterone was compared against the other quartiles and then the 2nd and 3rd quartiles against the 4th quartile. Results A total of 140 transfers were included in the analysis: 87 with β-HCG > 10 IU/L (62%), of which 50 (36%) delivered and 37 had a miscarriage (42%). Women with lower progesterone levels (< 10.7ng/mL) had a trend toward higher β-HCG-positive (72 versus 59%; p > 0.05), lower delivery (26 versus 39%; p > 0.05) and higher miscarriage rates (64 versus 33%; p < 0.01). Comparing the middle quartiles (P25–50) with those above percentiles 75, the rate of pregnancy was similar (60 versus 57%; p > 0.05), although there was a trend toward a higher number of deliveries (43 versus 31%; p > 0.05) and a lower number of miscarriages (28 versus 45%; p > 0.05). These differences were not statistically significant. Conclusion There were no differences in pregnancy and delivery rates related with the progesterone level when measured in the transfer day. The miscarriage rate was higher in the 1st quartile group.


2020 ◽  
Author(s):  
Elena Labarta ◽  
Giulia Mariani ◽  
Stefania Paolelli ◽  
Cristina Rodriguez-Varela ◽  
Carmina Vidal ◽  
...  

Abstract STUDY QUESTION Is there a serum progesterone (P) threshold on the day of embryo transfer (ET) in artificial endometrium preparation cycles below which the chances of ongoing pregnancy are reduced? SUMMARY ANSWER Serum P levels &lt;8.8 ng/ml on the day of ET lower ongoing pregnancy rate (OPR) in both own or donated oocyte cycles. WHAT IS KNOWN ALREADY We previously found that serum P levels &lt;9.2 ng/ml on the day of ET significantly decrease OPR in a sample of 211 oocyte donation recipients. Here, we assessed whether these results are applicable to all infertile patients under an artificial endometrial preparation cycle, regardless of the oocyte origin. STUDY DESIGN, SIZE, DURATION This prospective cohort study was performed between September 2017 and November 2018 and enrolled 1205 patients scheduled for ET after an artificial endometrial preparation cycle with estradiol valerate and micronized vaginal P (MVP, 400 mg twice daily). PARTICIPANTS/MATERIALS, SETTING, METHODS Patients ≤50 years old with a triple-layer endometrium ≥6.5 mm underwent transfer of one or two blastocysts. A total of 1150 patients treated with own oocytes without preimplantation genetic testing for aneuploidies (PGT-A) (n = 184), own oocytes with PGT-A (n = 308) or donated oocytes (n = 658) were analyzed. The primary endpoint was the OPR beyond pregnancy week 12 based on serum P levels measured immediately before ET. MAIN RESULTS AND THE ROLE OF CHANCE Women with serum P levels &lt;8.8 ng/ml (30th percentile) had a significantly lower OPR (36.6% vs 54.4%) and live birth rate (35.5% vs 52.0%) than the rest of the patients. Multivariate logistic regression showed that serum P &lt; 8.8 ng/ml was an independent factor influencing OPR in the overall population and in the three treatment groups. A significant negative correlation was observed between serum P levels and BMI, weight and time between the last P dose and blood tests and a positive correlation was found with age, height and number of days on HRT. Multivariate logistic regression showed that only body weight was an independent factor for presenting serum P levels &lt;8.8 ng/ml. Obstetrical and perinatal outcomes did not differ in patients with ongoing pregnancy regardless of serum P levels being above/below 8.8 ng/ml. LIMITATIONS, REASONS FOR CAUTION Only women with MVP were included. Extrapolation to other P administration forms needs to be validated. WIDER IMPLICATIONS OF THE FINDINGS This study identified the threshold of serum P as 8.8 ng/ml on the day of ET for artificial endometrial preparation cycles necessary to optimize outcomes, in cycles with own or donated oocytes. One-third of patients receiving MVP show inadequate levels of serum P that, in turn, impact the success of the ART cycle. Monitoring P levels in the mid-luteal phase is recommended when using MVP to adjust the doses according to the needs of the patient. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER NCT03272412.


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