Come in ogni edizione, la nostra équipe di medici e biologi del Servizio di Medicina della Riproduzione ha partecipato attivamente al 38° Congresso dell’ ESHRE (Società Europea di Riproduzione Umana ed Embriologia), tenutosi in questo mese di luglio a Milano. Di seguito una breve sintesi degli studi presentati dall’équipe di Dexeus Mujer.
- Precongress course – Progesterone levels in IVF cycles – when to measure and what to do according progesterone
Prof. Dr. N.P. Polyzos.
Dexeus University Hospital, Reproductive Medicine, Barcelona, Spain.
Progesterone supplementation is an essential part of assisted reproduction owing to the luteal phase defect observed either following ovarian stimulation for IVF/ICSI or in artificially prepared frozen embryo transfer cycles. Over the last decades different routes of progesterone administration have been utilized with differences in local and systemic absorption, pharmacokinetics and side effects.
The scope of the presentation is to present the novelties in the Luteal phase Support strategies in modern ART, the effect of progesterone formulations in fresh and frozen embryo transfer cycles and the new treatment strategies aiming towards and individualized Luteal phase support iLPS based on the measurement of serum progesterone levels.
- Invited session: State of ART of frozen embryo transfer cycles- Endometrial preparation for FET: HRT vs natural cycle
Prof. Dr. N.P. Polyzos.
Dexeus University Hospital, Reproductive Medicine, Barcelona, Spain.
Frozen-thawed embryo transfer (FET) cycles have increased dramatically over the past decade, mainly due to the introduction of vitrification as a more efficient method of cryopreservation, and the increase of freeze-all strategy in order to reduce the risk of OHSS.
Planning of FET cycles, is a key step for the implantation of the frozen-thawed embryos, since it allows the synchronization of the endometrium with the developmental stage of the embryo.
Endometrial preparation can be achieved either through hormonal replacement treatment (HRT) by an artificial cycle using exogenous estrogen administration for the development of the endometrium and subsequent administration of exogenous progesterone for its secretory transformation (AC-FET) or via a natural cycle, following the detection of LH surge (NC-FET), or the trigger of ovulation with human chorionic gonadotrophin (mNC-FET).
The scope of the presentation is to provide an overview of the different methods of endometrial preparation for FET cycles, their advantages and disadvantages, and the evidence regarding clinical but also adverse obstetrical and perinatal outcomes, following each different protocol.
- Elevated serum progesterone levels before frozen embryo transfer do not negatively impact reproductive outcomes: a large retrospective cohort study
Gonzalez-Foruria, S. García, A. Racca, M. Álvarez, N. Polyzos, B. Coroleu
Retrospective cohort study of 3183 blastocyst FET cycles under HRT performed in a university-affiliated fertility centre between March 2009 and December 2020. All the cycles presented adequate serum progesterone levels before FET (≥10.6 ng/ml). A total of 1360 cycles corresponded to frozen homologous embryo transfer (ET) (hom-FET), 1024 were euploid ET (eu-FET) after preimplantational genetic testing for aneuploidies (PGT-A), and 799 cycles were frozen heterologous ET (het-FET).The primary objective was live birth rate (LBR).
The results of this study suggest that once a threshold of serum progesterone before FET is achieved, progesterone levels are not predictive of the clinical outcome. Actually, LBR are not negatively affected when progesterone levels are found in their highest centiles after luteal phase rescue with vaginal plus subcutaneous progesterone.
- Adverse pregnancy and neonatal outcomes in an oocyte donation program. Expanded Carrier Screening can substantially decrease the risk of recessive conditions
Elisabet Clua, Gabriela Palacios i Marina Sumarroca
Expanded carrier screening (ECS) has been widely implemented in the screening of gamete donors. Nevertheless, pregnancies conceived after oocyte donation (OD) cycles are still at risk for genetic adverse outcomes. This is a retrospective observational study that analyses the adverse events reported in 4573 OD cycles carried out between January 2014 and December 2021 in the Reproductive Medicine Unit of Dexeus University Hospital. The study includes patients who underwent OD cycles and reported an adverse outcome with a potential genetic aetiology from 2014 to 2021.
Seventy-one recipients (1.55%) reported an adverse outcome of the pregnancy or children born from the OD. A confirmed genetic aetiology was reported in 23 (32.4%) cases including chromosomal abnormalities, microduplications and monogenic disorders. The reported remaining cases were due to congenital malformations, stillbirth, neurodevelopmental disorders, and other conditions for which a genetic aetiology has not been established to our knowledge.
Moreover, we identified 211 (4.6%) high-risk assignations due to oocyte donors and recipient’s male partners being carriers of the same autosomal recessive condition when initially assigned, which would have led to an additional 1,15% of children born with an autosomal recessive conditions (25% of 4.6% high-risk assignations). Additionally, we rejected 52 (3.07%) oocyte donor candidates that were carriers of X-linked conditions, which would have led to an additional 0.76% of children born with an X-linked disorder.
Based on our results, implementation of ECS, resulted in 55% risk reduction in adverse outcomes observed in our oocyte donation program from a potential adverse event rate of 3,46% to an actual 1.55% incidence of adverse outcomes.
- Association between polymorphisms in FSHR and reproductive outcomes following IVF. Secondary analysis of a prospective cohort study in Europe and Asia
Neves AR, Garcia S, Blockeel C, Arroyo G, Spits C, Pham TD, Ho MT, Tournaye H, Vuong NL, Polyzos NP
FSHR protein expression has been found in the placenta, umbilical cord, amnion and decidua, suggesting a role in the promotion of a healthy pregnancy. Previous reports have analysed the impact of FSHR SNP rs6166 in pregnancy outcomes with conflicting results, mainly due to the heterogeneity in the inclusion criteria and limited sample size.
We performed a secondary analysis of a multicenter multinational prospective study, including 368 patients from Vietnam, Belgium and Spain (168 from Europe and 200 from Asia) from 11/2016-06/2019. All patients underwent ovarian stimulation with fixed-dose 150IU rFSH in an antagonist protocol. Patients aged <38 years, undergoing their first or second IVF cycle with a predicted normal response were included. CPR, LBR and miscarriage rate (MR) in the first embryo transfer, as well as CLBR, were compared between the different genotypes of FSHR SNPs rs6166, rs6165 and rs1394205.
The results demonstrate a previously unreported association between variant FSHR SNPs rs6165 genotype GG and higher CPR and LBR and reinforce a potential role for the genetic background in the prediction of a favorable prognosis following IVF.
- Polymorphisms in FSHR gene do not affect late follicular phase steroidogenic response in predicted normoresponders. Secondary analysis of a prospective multicenter cohort study.
Neves AR, Blockeel C, Garcia S, Alviggi C, Spits C, Ma PQM, Ho MT, Tournaye H , Vuong NL, Polyzos NP.
Previous studies have shown that late follicular phase serum progesterone and estradiol levels are significantly correlated with the magnitude of ovarian response. Several authors have proposed that individual variability in the response to ovarian stimulation could be explained by variants in FSHR.
We performed a secondary analysis of a multicenter multinational prospective study, including 366 patients from Vietnam, Belgium and Spain (166 from Europe and 200 from Asia), conducted from 11/2016-06/2019. All patients underwent ovarian stimulation followed by oocyte retrieval in an antagonist protocol with a fixed daily dose of 150IU rFSH. Patients included were predicted normal responder women <38 years old undergoing their first or second ovarian stimulation cycle. All patients had a serum progesterone and estradiol measurement on the day of trigger and were genotyped for 3 FSHR SNPs (rs6165, rs6166, rs1394205).
Based on our results, FSHR SNPs rs6165, rs6166, rs1394205 do not influence late follicular phase serum progesterone nor estradiol levels in predicted normal responders. These findings add to the controversy in the literature regarding the impact of individual genetic susceptibility in response to ovarian stimulation in this population.
- Microgravity exposure significantly decreases sperm motility and vitality. Can we consider human reproduction outside the Earth?
Boada M, Perez-Poch A, Ballester M, Tresanchez M, Sánchez E, Martínez G, González DV, García S., Torner J, Polyzos NP
Microgravity effects on the male reproductive system have mainly been studied in the animal model with diverse results and discouraging extrapolation in humans.
Prospective study carried out in collaboration between the ART centre, a Technical University, and an Aviation Club specializing in parabolic flights. Two parabolic flights were conducted between 2020-2021, each consisting of 20 parabolic maneuvers, which means 160 seconds of microgravity exposure per sample. Fifteen sperm samples obtained from healthy men were included in the study in order to analyse the effects of microgravity and compare the results with those obtained in Earth gravity.
On comparison of the mean values between fresh samples exposed to microgravity and those maintained on Earth gravity, statistical significant differences were found in the following parameters: vitality, motile sperm concentration, grade “a” sperm concentration, percentage of spermatozoa with progressive motility, curvilinear motility-VCL. Under the study conditions, non-statistically significant differences were observed in the other kinematic parameters.
Motility and vitality of fresh human sperm samples are significantly decreased under microgravity conditions obtained by parabolic flight. Short exposure to microgravity significantly decreases sperm motility and vitality so such an effect is likely to be stronger with longer exposure. These findings should be taken into account when reproduction outside the Earth is intended since this may eventually affect sperm fertilizing capacity and therefore ART with fresh or frozen sperm samples.
- Quality of life and Sexual Dysfunction in Bologna poor ovarian responders
Hernandez Hernandez, S. García, F. Martínez, N.P. Polyzos
Diagnosis of infertility is a common cause of sexual health disorders. Couples undergoing Assisted Reproductive Technology (ART) can face emotional stress and feelings of inadequacy or guilt that may interfere in their quality life and sexual function.
In a prospective study conducted between 2015 and 2021 we collected questionnaires from poor ovarian responders fulfilling the Bologna criteria concerning their quality of life and sexual function.
Patients’ mean age was 38.6 years old (with 20.6% of the patients being under 35, 33.8% between 35-39 and 45.6% were above 40 years). Infertility duration was less than a year for 22.1% of patients and over one year for 77.9% of patients. Most of patients (80.9%) had at least one previous IVF/ICSI treatment.
Quality of life was significantly lower among poor responders with previous IVF attempts, whereas sexual distress was higher in women with previous IVF/ICSI treatment and women with longer duration of infertility.
Conclusion: Social and sexual concerns should be taken in consideration in Bologna poor responders, especially in those with longer duration of infertility and previous failed IVF attempts independent of their age.
- Progesterone supplementation in frozen embryo transfer with hormonal replacement therapy is associated with higher incidence of macrosomia
Racca A, Prats P, Garcia S, Alvarez M, Coroleu B, Polyzos NP
In total 406 cycles with singleton pregnancy and delivery in our clinic were included in this analysis. 277 cycles showed a progesterone values > 10.6 ng/mL on the day before the embryo transfer, while 129 cycles needed to be supplemented with either extra-vaginal or subcutaneous supplementation from the day of embryo transfer (because progesterone <10.6 ng/mL).
The patients baseline characteristics were comparable between the two groups. The findings of this study showed and higher incidence of macrosomia in the group where progesterone was supplemented. This finding, clinically nonessential, needs to be more investigated, especially from a physiological point of view.
Looking at the 129 supplemented cycles where progesterone was supplemented, there was no association with progesterone supplementation and pre-eclampsia.