Serum progesterone concentration on day of embryo transfer in donor oocyte cycles

Purpose

To evaluate the association between serum progesterone (P) levels on the day of embryo transfer (ET) and pregnancy rates in fresh donor IVF/ICSI cycles.

Methods

Fresh donor cycles with day 3 ET from 10/2007 to 8/2012 were included (n = 229). Most cycles (93 %) were programmed with a gonadotropin releasing hormone (GnRH) agonist; oral, vaginal or transdermal estradiol was used for endometrial priming, and intramuscular P was used for luteal support (50–100 mg/day). Recipient P levels were measured at ET, and P dose was increased by 50–100 % if <20 ng/mL per clinic practice. The main outcome measure was rate of live birth (> = 24 weeks gestational age). Generalized estimating equations were used to account for multiple cycles from the same recipient, adjusted a priori for recipient and donor age.

Results

Mean recipient serum P at ET was 25.5 ± 10.1 ng/mL. Recipients with P < 20 ng/mL at ET, despite P dose increases after ET, were less likely to achieve clinical pregnancy (RR = 0.75, 95 % CI = 0.60–0.94, p = 0.01) and live birth (RR = 0.77, 95 % CI = 0.60–0.98, p = 0.04), as compared to those with P ≥ 20 ng/mL. P dose increases were more often required in overweight and obese recipients.

Conclusions

Serum P levels on the day of ET in fresh donor IVF/ICSI cycles were positively correlated with clinical pregnancy and live birth rates. An increase in P dose after ET was insufficient to rescue pregnancy rates. Overweight and obese recipients may require higher initial doses of P supplementation. Future research is needed to define optimal serum P at ET and the interventions to achieve this target.     

Recurrent implantation failure: definition

Purpose An attempt to define recurrent implantation failure. Methods Literature review. Results Numerous definitions of recurrent implantation failure exist. The complexity and redundancy of the process of implantation makes a single definition difficult to determine. Conclusion Each center must establish a definition of recurrent implantation failure based upon the data from that center. The definition of RIF used in our program requires the transfer of ≥8, 8-cell stage embryos or ≥5 blastocyst embryos. Implantation failure must be defined by each IVF center based upon the data from that center.     

体外受精-胚胎移植周期中注射人绒毛膜促性腺激素日患者血清孕酮水平与妊娠结局的相关性

目的 探讨体外受精-胚胎移植(IVF-ET)周期中注射人绒毛膜促性腺激素(hCG)日患者血清孕酮水平与临床妊娠结局的相关性.方法 对2002年3月-2007年4月在南京医科大学第一附属医院生殖医学科注射hCG日有血清孕酮水平检测结果的786个IVF周期进行回顾性分析.每个周期均采用促性腺激素释放激素激动剂(GnRH-a)降调节,采用促性腺激素(Gn)促排卵.将孕酮水平为5.5、6.0、6.5、7.0、7.5、8.0、8.5和9.0 nmol/L设定为不同界值,孕酮水平<相应界值者为低孕酮水平,≥相应界值者为高孕酮水平,分别比较采用不同界值时高、低孕酮水平患者的各项实验室及临床检测指标.结果 786个周期中,采用不同的孕酮水平界值时,注射hCG日高孕酮水平与低孕酮水平患者的正常受精率、优质胚胎率、种植率、生化妊娠率、临床妊娠率、活产率比较,差异均无统计学意义(P>0.05);以8.5及9.0 nmol/L为孕酮水平界值时,高孕酮水平患者的早期流产率分别为27.3%(3/11)和3/7,均高于低孕酮水平者[分别为8.8%(26/297)和8.6%(26/301)],差异均有统计学意义(P<0.05);以9.0 nmol/L为孕酮水平界值时,高孕酮水平患者的总流产率为3/7,高于低孕酮水平者[11.0%(34/301)],差异也有统计学意义(P<0.05).结论 注射hCG日血清孕酮水平与临床妊娠率及活产率无关,当以8.5或9.0 nmol/L为孕酮水平界值时,早期流产率或总流产率与高孕酮水平相关.     

Association of progesterone receptor polymorphisms with recurrent implantation failure after in vitro fertilization and embryo transfer

Introduction Progesterone is the hormone of pregnancy and is required for its initiation. The actions of progesterone are mediated by the progesterone receptor. Polymorphic variants of human progesterone receptor genes have been implicated in implantation failure. Materials and methods We, therefore, investigated the prevalence of H770H(C/T genotype), V660L polymorphism and a 306 bp Alu insertion in exon 7 of the progesterone receptor among women with history of recurrent implantation failure to determine whether any of these polymorphisms may serve as a risk factor for implantation failure. DNA was extracted from the buccal swabs obtained from 66 women experiencing implantation failure and 75 fertile control women. PCR amplification of fragments was purified and the DNA sequenced to identify the polymorphism. The frequencies for the three variants were 27% for H770H, 21% for V660L and 0% for the 306 bp Alu insertion in exon 7 among women with implantation failure compared with control women of 25% for H770H and 24%for V660L and 0% for the 306 bp Alu insertion in exon 7. Discussion No significant differences in the overall allelic frequency of progesterone receptor variants was seen when women experiencing recurrent implantation failure were compared with control women. Conclusion We conclude that the H770H and V660L and PROGINS progesterone receptor polymorphisms are not markers that can identify women at risk for recurrent implantation after IVF/ET. Capsule H770H, V660L and PROGINS progesterone receptor polymorphisms were not found to be associated with recurrent implantation failure after IVF/ET.     

Both high and low HCG day progesterone concentrations negatively affect live birth rates in IVF/ICSI cycles

Research questionCan previous reports of a decreased probability of success in stimulated IVF cycles with premature rise of progesterone, as determined by progesterone concentration on HCG day (PHCG), be confirmed?DesignRetrospective, observational, single-centre cohort study conducted on 5447 IVF and intracytoplasmic (ICSI) cycles carried out among 2192 patients between 2009 and 2015, with conventional ovarian stimulation. This large database was used to develop a non-linear mixed prognosis model of live birth rate (LBR) incorporating PHCG as a predictor.ResultsIn addition to known predictors (age, body mass index, anti-Müllerian hormone, type of infertility), PHCG was associated with a linear effect (OR 0.78 per Log[PHCG]ng/ml, 95% CI 0.611 to 0.997, P = 0.047) combined with a strong quadratic effect (OR 0.585 per Log²(PHCG)ng/ml, 95% CI 0.444 to 0.775, P < 0.001) resulting into a parabolic reverse-U curve. A significant interaction (P = 0.038) was found between PHCG and number of oocytes if three or less, but the effect of PHCG remains modest. For higher oocyte numbers, LBR rapidly increases with number of retrieved oocytes; however, LBR becomes more sensitive to PHCG as the number of oocytes increases. Higher live birth prognoses occur for optimal PHCG but are sharply reduced for lower or higher PHCG.ConclusionsEvidence is provided of an important negative effect of PHCG at lower and higher values, independent of oocyte number, thus defining appropriate ranges for fresh embryo transfer or freeze-all strategy. In poor responders, premature progesterone rise may be ignored, thus avoiding unnecessary cancellations or embryo freezing. Conversely, in higher responders, the negative effect of progesterone elevation is more pronounced, suggesting that freeze-all policy should be applied more widely.     

Embryo quality but not pronuclear score is associated with clinical pregnancy following IVF

Purpose

The association between pronuclear (PN) scoring of embryos from assisted reproductive technology (ART) and clinical pregnancy remains controversial. We hypothesized that embryos with PNs scored on the day of fertilization check offer better embryo selection on day 3 and higher CPR compared to non-PN scored embryos.

Methods

Patients (19–46 years) undergoing IVF/ICSI cycles at Montefiore’s Institute for Reproductive Medicine and Health between January 2006 and December 2009 were included in our study. We analyzed fresh day 3 cycles only with autologous oocytes and partner’s fresh sperm (n = 344). A total of 1,899 embryos were included. We compared CPR from non-PN scored embryos (Group 1, n = 835) with PN scored embryos (Group 2, n = 1,064). Composite scores by patient were developed based on embryo disposition. We also assessed traditional embryo grading derived from cell number, fragmentation and cell symmetry. Data analysis included chi square and t test to determine if PN scoring was associated with improved CPR, and to compare the additional variables.

Results

CPR between Group 1 and Group 2 were not different (p = 0.91). CPR was significantly associated with female age, number of mature oocytes retrieved, number of day 3 embryos and grade of embryos transferred on day 3 (p < 0.05).

Conclusion

PN scoring was not associated with improved CPR in day 3 embryo transfers. Mean grade of transferred embryos continues to be a well-established, independent predictor of CPR. We conclude that further refinement of embryo grading by PN scoring is not beneficial.     

Effect of powdered gloves,worn at the time of embryo transfer,on the pregnancy outcome of IVF cycles

Purpose  To assess the effect of wearing powdered gloves during embryo transfer as compared to un-powdered gloves on the pregnancy outcome of IVF cycles. Methods  Patients, undergoing embryo transfer procedures, were prospectively randomized into two groups: In the first (group A, n=356) group embryo transfer was performed while wearing powdered gloves; in the second (group B, n=356) group embryo transfer was performed while wearing un-powdered gloves. The primary end point of the study was the clinical pregnancy rate. Results  The two groups were comparable with respect to the mean age, mean number of grade one embryos obtained, and the mean number of embryos transferred. The clinical pregnancy rates of the two groups were not different. Conclusions  Powdered gloves, worn during embryo transfer, have no adverse effect on the pregnancy outcome of IVF cycles. Capsule   Powdered gloves, worn during embryo transfer, have no adverse effect on the pregnancy outcome of IVF cycles.     

Endometrial scratching for women with previous IVF failure undergoing IVF treatment

Abstract

The purpose of this study was to find out whether endometrial scratching could improve live birth rate in women with previous IVF failure undergoing fresh IVF cycle. In a randomized controlled trial, 387women with previous IVF failure were divided into two groups. Group A (193 women) was subjected to endometrial biopsy procedure twice. Group B (194 women) was subjected to a placebo procedure. Our results showed no difference in live birth rate between the two groups of women (47.2% versus 38.1%, p?=?0.08). However, regression analysis revealed that endometrial scratching was an independent predictor of live birth in the subgroup of women with two or more previous failure after control of other independent predictors (odds ratio (OR) 3.4, p?=?0.005). We conclude that endometrial scratching does not improve live birth rate in women undergoing IVF treatment with previous one IVF failure. Nevertheless, it may improve live birth in women with two or more previous IVF failures.     

体外受精与胚胎移植中hCG注射前血孕酮水平与妊娠的关系

用ＧｎＲＨａ－ＦＳＨ－ｈＭＧ－ｈＣＧ方案控制性超排卵进行体外受精与胚胎移植（ＩＶＦ－ＥＴ）治疗７８例不孕患者，在ｈＣＧ注射前抽血用放射免疫法（ＲＩＡ）测孕酮（Ｐ）水平。初步了解ｈＣＧ注射时血孕酮水平与ＩＶＦ－ＥＴ结果的关系。结果，当Ｐ〈０．３５μｇ／Ｌ时９例中无１例妊娠，而０．３５≤Ｐ≤０．９μｇ／Ｌ组（５４例）与Ｐ〉０．９μｇ／Ｌ组（１５例）的妊娠率分别为２２．６％及２６．７％，但三组间无显著差     

Evaluating the benefit of measuring serum progesterone prior to the administration of HCG: effect of the duration of late-follicular elevated progesterone following ovarian stimulation on fresh embryo transfer live birth rates

Research question

Progesterone overproduction during ovarian stimulation is associated with lower live birth rates (LBR) after fresh embryo transfer. Therefore, circulating P concentrations on the day of HCG administration are frequently measured in clinical practice and followed by an elective cryopreservation strategy whenever late-follicular elevated P (LFEP) occurs. A recent study concluded that the duration of LFEP >1.00 ng/mL prior to HCG administration may also affect clinical pregnancy rates. The objective of this current study was to assess whether this hypothesis was reproducible using LBR as the primary outcome.

The effect of endometrial thickness on the day of hCG administration on pregnancy outcome in the first fresh IVF/ICSI cycle

The aim of this study was to investigate the effect of endometrial thickness (EMT) on human chorionic gonadotropin (hCG) day on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcome. A retrospective study was conducted on the clinical data of 756 patients in their first fresh IVF/ICSI cycle at the Wuxi Maternity and Child Health Hospital. Compared with the pregnancy failure group, the clinical pregnancy group had more transferable embryos and good-quality embryos and had a thicker endometrium (p?<?0.05). The endometrial pattern was not significantly different between the two groups. EMT was found to be an independent prognostic factor for clinical pregnancy (adjusted OR?=?1.25, 95% CI: 1.15–1.36, p?<?0.01). Seven hundred and fifty-six cycles were categorized into three groups upon EMT on the hCG day: group 1 (EMT??14?mm). Group1 had significantly lower clinical pregnancy, embryo implantation and live birth rates compared with group 2 and 3 (p?<?0.01), while there was no significant difference in either spontaneous abortion or multiple-birth rate among these three groups. It was concluded that EMT on the hCG day was associated with pregnancy outcome in the first fresh IVF/ICSI cycle. A higher clinical pregnancy rate could be achieved when EMT?≥?8?mm, and no adverse pregnancy outcome was observed when EMT?>?14?mm.     

Quality of embryos transferred and progesterone levels are the most important predictors of live birth after fresh embryo transfer: a retrospective cohort study

Purpose

To identify the independent predictors of live birth following IVF, and to assess the role of cohort-specific parameters, including antral follicle count (AFC), the number of oocytes retrieved, the total number of embryos, and the total number of good-quality embryos, in fresh IVF cycles.

Methods

A retrospective cohort study of 2,525 infertile women undergoing IVF between 2002 and 2007. The hypothesis that the number and quality of embryos transferred capture the effects previously attributed to cohort-specific variables was examined using mediation analysis and spline analysis. Independent predictors were identified by a bootstrap algorithm. Multivariable logistic regression was performed and the proportion of explained variation was measured to compare the relative importance of transfer-specific vs. cohort-specific predictors.

Results

The number of good-quality embryos transferred and progesterone level on the day of hCG administration ranked as the two most important predictors of live birth. Prospects of pregnancy started to decrease after progesterone level exceeded 0.6 ng/ml. The achievement of live birth in a fresh IVF cycle is primarily determined by the number and quality of embryos transferred, rather than by embryo cohort-specific variables.

Conclusions

The associations between cohort-specific variables and live birth in a fresh IVF cycle are completely mediated by the quality of embryos transferred. Progesterone level on the day of hCG administration is an independent predictor of pregnancy and merits further investigation.     

Obstetric and perinatal outcomes of pregnancy in patients with repeated implantation failure

ObjectiveDespite the great advance of assisted reproductive technology (ART) in recent decades, many IVF patients failed to achieve a pregnancy even after multiple IVF-ET attempts. These patients are considered to have repeated implantation failure (RIF). While exhausting efforts have been devoted to the improvement of pregnancy rate in RIF patients, it is not clear whether RIF patients have aberrant obstetric or perinatal outcomes after they eventually achieved a pregnancy.Materials and methodsTaking advantage of a relatively large database of IVF-ET cycles at the Chang Gung Memorial Hospital, we compared obstetric and perinatal outcomes of RIF patients who have a successful pregnancy after IVF-ET treatment(s) to those of control IVF-ET patients.ResultsBecause multiple pregnancies are associated with a high risk of obstetric complications, we restricted the analysis to patients who had singleton pregnancies. Analysis of a total of 596 control and 46 RIF cases showed the rates of almost all obstetric and perinatal outcomes investigated are not different between the two groups. However, the rate of placental abruption in the RIF group (4.35%) appeared to be significantly higher than that of controls (0.50%; OR = 8.99). This difference is still statistically significant after adjustment with the age (adjusted OR = 8.2).ConclusionWhile the rates of a spectrum of obstetric and perinatal outcomes are normal in RIF patients, these patients could have an enhanced risk of placental abruption. However, investigations with a large sample size are needed to substantiate this inference.     

Low serum progesterone the day prior to frozen embryo transfer of euploid embryos is associated with significant reduction in live birth rates

Abstract

A retrospective cohort study was performed to examine whether, in artificial endometrial preparation for frozen embryo transfer (FET) cycles, progesterone (P) levels the day prior to embryo transfer of euploid embryos have an impact on pregnancy outcomes. In a private university clinic, 244 FETs between January 2016 and June 2017 were analyzed. Endometrial preparation was achieved with estradiol valerate and vaginal micronized progesterone. Serum P and estradiol levels the day prior to embryo transfer were measured. A multivariable analysis to assess the relationship between serum P level and pregnancy outcomes was performed, adjusted for confounding variables. Mean P value was 11.3?±?5.1?ng/ml. Progesterone levels were split in quartiles: Q1: ≤ 8.06?ng/ml; Q2: 8.07–10.64?ng/ml; Q3: 10.65–13.13?ng/ml; Q4: > 13.13?ng/ml. Patients included in the lower P quartile had a significantly higher miscarriage rate and significantly lower live birth rate (LBR) compared to the higher ones. A low serum P level (≤ 10.64?ng/ml) one day before FET is associated with a lower pregnancy and LBR following FET of euploid embryos.     

Serum progesterone concentration on day of HCG administration and IVF outcome

To determine the relationship between serum progesterone on the day of human chorionic gonadotrophin (HCG) and the pregnancy outcome of IVF-embryo transfer treatment, 251 infertile patients undergoing IVF-embryo transfer with gonadotrophin-releasing hormone agonist (GnRHa) and recombinant FSH (rFSH) were prospectively studied. Among them, 118 patients underwent 118 cycles of frozen embryo transfer (FET) treatment, one cycle per patient. All the cycles were grouped according to serum progesterone concentration on the day of HCG administration (<3.97 nmol/l or >/=3.97 nmol/l). The incidence of progesterone elevation was 36.7% (92/251), and in this group the pregnancy rate was significantly lower (25.97 versus 48.57%; P < 0.001). If the serum progesterone on the day of HCG was over 6.0 nmol/l, their pregnancy outcome was much poorer (13.79 versus 44.68%). However, the pregnancy rate was similar in FET cycles whether the serum progesterone was over 3.97 nmol/l (34.00 versus 36.76%) or 6.0 nmol/l (42.86 versus 34.02%). In conclusion, serum progesterone on the day of HCG may predict IVF pregnancy outcome. The higher serum oestradiol and progesterone concentrations may affect endometrial receptivity. For patients with an extremely high progesterone concentration on the day of HCG (such as over 6.0 nmol/l), transfer of frozen embryos in a natural cycle is suggested.     

诱发日内源性孕酮升高对PCOS患者的IVF/ICSI临床结局的影响

目的:在高孕激素超促排卵(progestin-primed ovarian stimulation,PPOS)及全胚胎冷冻移植的背景下,探讨诱发排卵日内源性孕酮(P)水平与多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者体外受精/卵胞质内单精子显微注射(IVF/ICSI)临床结局的关系。方法:回顾性纳入180例PCOS患者行IVF/ICSI-冻融胚胎移植(FET)的资料,所有患者均采用促性腺激素(gonadtropin,Gn)联合孕激素的超促排卵方案,取卵后全部胚胎冷冻,择期行FET,根据诱发排卵日P水平分为A组(P1.0μg/L,n=125)和B组(P≥1.0μg/L,n=55),比较两组患者的促排卵结局和妊娠结局。结果:A组与B组的Gn总用量(1950.8±384.5 IU vs 1931.2±308.9 IU)及周期治疗时间(11.2±1.4 d vs 11.1±1.1 d)均无统计学差异(P0.05)。A组诱发日直径14 mm卵泡数(14.1±7.7 vs21.0±10.3)、获卵数(14.0±7.8 vs 24.1±10.3)、成熟卵数(12.1±7.1 vs 21.1±9.0)、正常受精卵数(9.8±6.1 vs 16.8±8.2)及冷冻胚胎数(5.3±3.6 vs 7.2±3.4)均较B组低,且差异均具有统计学意义。成熟卵率、正常受精卵率、周期取消率、临床妊娠率及种植率组间均无统计学差异(P0.05)。结论:在FET的前提下,高孕激素超促排卵过程中诱发日内源性P水平的升高提示卵巢反应良好,对PCOS患者的IVF/ICSI临床结局无明显影响。     

Prognostic value of growth of 4-cell embryos on the day of transfer in fresh IVF-ET cycles

Purpose

To investigate the prognostic value of growth of 4-cell embryos on the day of transfer in determining clinical pregnancy and live birth rates after fresh in vitro fertilization (IVF)-embryo transfer (ET) cycles.

Methods

Retrospective cohort study of all patients between January 2008 and January 2013 initiating fresh IVF-ET cycles resulting in embryos that were not more than 4 cells 72 h after oocyte retrieval in the morning of their transfer. Patients were stratified into 2 groups based on whether embryos did or did not grow more than the 4-cell stage on the afternoon of ET. The odds of clinical pregnancy and live birth were considered as primary outcomes. Student’s t-tests and Chi-square (χ2) tests were used as inidicated, with logistic regression controlling for maternal age and number of embryos transferred.

Results

Three hundred forty three patients were identified for inclusion: 165 and 178 patients had 4-cell embryos with and without growth on the afternoon of ET, respectively. The demographic and baseline IVF cycle characteristics of the study cohort were comparable. Patients with embryo growth had higher clinical pregnancy (13.9 % vs. 4.49 %) and live birth (10.9 % vs. 3.37 %) rates compared to patients without embryo growth. This represented an overall increased odds of clinical pregnancy [Odds ratio (OR) = 3.44; 95 % Confidence Intervals (CI) 1.49–7.93; P = 0.004)] and live birth (OR = 3.51; 95 % CI 1.36–9.07; P = 0.01). The increased odds remained unchanged after adjusting for maternal age and number of embryos transferred.

Conclusions

Transfer of 4-cell embryos 3 days after oocyte retrieval can result in clinical pregnancies and live births, albeit at a low rate. Growth of an embryo more than the 4-cell stage on the afternoon of ET may serve as a positive prognostic factor for IVF-ET cycle outcome.