Timed intercourse in association with controlled ovarian hyperstimulation as the first-line treatment of couples with unexplained subfertility.

OBJECTIVE: To report on the pregnancy outcomes of timed intercourse (TI) with controlled ovarian hyperstimulation (COH) as the first-line treatment of unexplained subfertility, and provide some evidence on the factors involved. METHODS: The records of couples treated between January 2016 and March 2019 were retrospectively analyzed. Couples were selected for TI based on standard infertility evaluation. Semen analysis by swim-up was conducted and the total motile sperm count (TMSC) obtained. The main outcome measured was the clinical pregnancy rates. Data were analyzed with t test, Pearson's Chi-squared test, and the Wald test for logistic regression with p≤0.05. RESULTS: The records of 275 couples (449 cycles) were included in the analysis. Patients underwent TI up to six attempts. Patient- and cycle-based pregnancy rates were 18.55% and 13.14%, respectively. Eight patients got pregnant twice, resulting in a cumulative pregnancy rate of 21.4%. Women that did not get pregnant demonstrated a statistically higher mean age value than women who did (p=0.0186). Logistic regression indicated that for every year added to the woman's age, the chances of pregnancy reduced by 6.45%, and for cycles with TMSC ≥ 5 million, the chances of pregnancy were 1.91 times higher when compared to TMSC < 5 million. CONCLUSIONS: TI with COH should be considered as the first-line treatment for selected couples with unexplained subfertility before more traumatic and costly IVF treatments were considered. The findings can assist doctors to conduct a more educated counselling concerning the chances patients have to get pregnant with TI.

Efficacy of a modified transvaginal ultrasound-guided fresh embryo transfer procedure.

OBJECTIVE: To present a modified transvaginal ultrasound (TVUS) guided embryo transfer (ET) procedure and analyze its efficacy in comparison with conventional transabdominal ultrasound (TAUS) guided ET in an unselected population of Brazilian women. METHODS: This retrospective observational case-control study involved 447 fresh ET cycles, 221 guided by TVUS (Group 1), conducted between June 2016 and February 2019, and 226 by TAUS (Group 2), conducted between July 2012 and December 2015. Pregnancy rate was the main endpoint. Groups were compared using the Z test at a level of significance of 95% (p≤0.05). RESULTS: Patient age ranged from 21 and 48 years; mean age was 37.7 years in Group 1 and 38 years in Group 2. Overall, patients that underwent TVUS-guided fresh ET demonstrated significantly higher pregnancy rates than their counterparts that underwent TAUS-guided fresh ET (p=0.0107). TVUS-guided fresh ET also yielded significantly higher pregnancy rates in the subgroups of women aged 36-39 years (p=0.0037) and ≥ 40 years (p=0.0025). However, no significant pregnancy rate difference was observed in women aged ≤ 35 years (p=0.0905). CONCLUSIONS: The results suggested that TVUS-guided fresh ET was at least as effective as TAUS-guided fresh ET in the studied sample. Pending further prospective studies to better ascertain the effect of TVUS-guided ET, the technique presented deserves consideration since it can offer better visualization, more comfort to patients, and requires only one operator, without negatively affecting pregnancy results.

Relationship between age and blastocyst chromosomal ploidy analyzed by noninvasive preimplantation genetic testing for aneuploidies (niPGT-A).

OBJECTIVE: To assess the relationship between human blastocyst chromosomal ploidy established by niPGT-A and increasing age. METHODS: This is a prospective multicenter study carried out by ten assisted reproduction centers after their embryologists acquired training and validated their results with the previous use of niPGT-A. A total of 94 couples with indication for niPGT-A due to increase maternal age, male factor, repeated implantation failures, recurrent abortion or because they requested niPGT-A were included in this study. The couples had no karyotype abnormalities. After ICSI, the embryos were cultured until blastocyst stage using one or two step culture systems, single or sequential media respectively, at 37°C in an atmosphere of 6-7% CO2 and 5-20% O2 incubators. On day 3, we re-evaluated cleavage embryos to complete cumulus cells removal. The embryos were then cultured in individual well, with 20µl of medium under oil until they reached blastocyst stage. The blastocysts were vitrified and stored in liquid nitrogen. After that, the spent blastocyst culture medium (20µl) was transferred to a PCR tube and sent for analysis in the genetic laboratory, where it was stored at -80°C until sequencing. A total of 243 samples of spent blastocyst culture medium were collected on the 5th/6th day. Cell-free DNA secreted on culture medium was amplified using NICS Sample Preparation Kit (Yikon Genomics), based on the MALBAC technology. After whole genome amplification, the DNA was measured using a Qubit 2.0 fluorometer and subjected to next generation sequencing (NGS) using Illumina MiSeq® platform. The data were analyzed using the ChromGo® software (Yikon Genomics). RESULTS: The mean age of the patients was 38±4.08 years with an interval of 20-44 years. The euploid was diagnosed in 36.4% (80/220) of cases, aneuploidy in 31.3% (69/220), and mosaicism in 32.3% (71/220; with ≥60% aneuploidy) of blastocysts. Mosaic values ranged from 29.8% to 33.8% in different age groups. Individually, the most frequent chromosomal abnormality was XXY (Klinefelter Syndrome) occurring in 18 cases, followed by chromosome 21 (trisomy/monosomy) in 8 cases. The niPGT-A data showed a ≥60% incidence of aneuploid cells in all cases of chromosomal mosaicism (n=71). CONCLUSION: A high degree of mosaicism with aneuploidy cells was detected, and some hypotheses were suggested for this data (niPGT-A sensitivity in detecting the self-correction of chromosomal abnormalities phenomenon). However, it did not vary remarkably with age. On the other hand, euploidy levels had a negative correlation with age and aneuploidy levels had a positive relationship. This is the first report in the literature to relate chromosomal ploidy in blastocysts using niPGT-A and increasing patient age.

Vitrification of Human Oocytes and its Contribution to In Vitro Fertilization Programs.

OBJETICVE: To study the cumulative pregnancy outcome, particularly in terms of live births, with the consecutive transfer of embryos from fresh and vitrified/warmed oocytes to infertile patients in a routine infertility program. METHODS: Patients were initially submitted to in vitro fertilization embryo transfer with fresh embryos, while surplus oocytes were vitrified with the Vitri-Ingá method. Patients who did not succeed to carry their gestation to term underwent a new cycle with embryos from their own warmed oocytes. Some of the patients participating in the first warming cycle, who still possessed surplus oocytes, underwent a second warming cycle. Clinical and pregnancy outcomes obtained with fresh and warming cycles were compared using the chi-square test at a level of significance of 5%. RESULTS: Of the 211 participating patients, 97 (46%) got pregnant with fresh embryo transfer, and 69 (32.7%) carried their pregnancies to term. Of the patients participating in the first and second warming cycles, 32/100 (32%) and 6/20 (30.0%) resulted in live births, respectively. Thus, of the 211 participating patients, 107 carried their pregnancies to term, representing a cumulative live birth rate of 50.7%. No statistically significant differences between the use fresh and vitrified oocytes were found for any of the variables studied. CONCLUSIONS: Oocyte vitrification offered the possibility of gestation in more than one attempt after just one controlled hyperstimulation. Apart from alleviating the financial burden on patients, vitrification of oocytes may result in a feasible solution for the problems generated by abandoned frozen embryos.

Uso de análogo GnRH/LH-RH acetado de leuprolide na induçäo da ovulaçäo na fertilizaçäo in vitro (FIV) e transferência intratubária de gametas (GIFT) / Use of the GnRH/LH-RH analog leuprelide acetate on ovulation induction for in vitro fertilization (IVF) and gamete intrafallopian transfer (GIFT)

Os autores apresentam os resultados obtidos em 14 casos de FIV e três casos de GIFT. Todas as pacientes haviam sido estimuladas anteriormente por diferentes indutores e estavam catalogas no grupo de resposta pobre. Foi usado um protocolo onde o análogo LH-RH, acetato de leuprolide, começou a ser administrado na fase lútea do ciclo anterior. Este protocolo foi comparado com um grupo controle em que foi utilizado o citrato de clomifene e hMG. Foram obtidas três gestaçöes no grupo tratado com acetato de leuprolide. A análise dos resultados mostra que o uso deste análogo na induçäo dos casos de Reproduçäo Assistida é extremamente útil, pois o número de oócitos e o índice de fertilizaçäo säo maiores