2019年1月31日

習慣性流產病患夫妻雙方染色體異常率約5-10%

 2018 Nov 23. doi: 10.1007/s10815-018-1373-4. [Epub ahead of print]

Chromosomal abnormalities in couples with recurrent spontaneous miscarriage: a 21-year retrospective study, a report of a novel insertion, and a literature review.

Abstract

PURPOSE:

The aim of this study is to evaluate the frequency and nature of chromosomal abnormalities in Moroccan couples with recurrent spontaneous miscarriage (RSM). In addition, the data were compared with those reported elsewhere in order to give a global estimation of chromosomal abnormalities frequencies.

METHODS:

The study was performed for all couples with RSM who were referred to the cytogenetic department, Pasteur Institute of Morocco, from different hospitals in Morocco between 1996 and 2016. Cytogenetic analysis was performed according to the standard method.

RESULTS:

Among 627 couples with RSM, the chromosomal abnormalities were identified in 11.00% of couples, with chromosomal inversions in 4.30%, reciprocal translocations in 2.71%, Robertsonian translocations in 1.43%, and deletion, isochromosome, and insertion in 0.15% each. The insertion identified [46,XX,ins(6)(p24q21q27)] is new, and is the fourth reported in association with RSM. The mosaic karyotypes were observed in 0.64%, polymorphic variants were identified in 1.27%, and numerical aneuploidy was observed in 0.15%. In regrouping our results with those in 27 other studies already published in 21 different countries, we obtained the frequency of chromosomal abnormalities in couple with RSM to be 5.16% (991/19197 couples). The reciprocal translocation was the most frequent with 2.50%, followed by Robertsonian translocation 0.83% and inversions 0.77%. The other types of chromosomal abnormalities were present with 0.98% in the world.

CONCLUSION:

This data showed that the frequency of chromosomal abnormalities in Moroccan couples with RSM is 11.00%, and in regrouping our results with other studies, the frequency changes to 5.16%.
注射骨髓間葉幹細胞於母馬卵巢並無法有效改善卵巢功能&卵泡數量
 2018 Nov 23. doi: 10.1007/s10815-018-1371-6. [Epub ahead of print]

Effect of intra-ovarian injection of mesenchymal stem cells in aged mares.

Abstract

PURPOSE:

This study aims to determine if intra-ovarian injection of bone marrow-derived mesenchymal stem cells (MSCs) improves or restores ovarian function in aged females.

METHODS:

Prospective randomized study of eight aged mares and six young mares receiving intra-ovarian injection of MSCs or vehicle. Main outcome measures were antral follicle count and serum anti-Müllerian hormone (AMH) (aged and young mares), and for aged mares, oocyte meiotic and developmental competence; gross and histological ovarian assessment; evaluation of presence of chimerism in recovered granulosa cells and in ovarian tissue samples; and gene expression in ovarian tissue as assessed by RNA sequencing.

RESULTS:

Injection of MSCs was not associated with significant changes in follicle number, oocyte recovery rate on follicle aspiration, oocyte maturation rate, or blastocyst rate after ICSI in aged mares, or in changes in follicle number in young mares. There were no significant changes in peripheral AMH concentrations, indicating a lack of effect on growing follicles. MSC donor DNA was not recovered in granulosa cells or in ovarian tissue, indicating lack of persistence of injected MSC. RNA sequencing revealed significant differences in gene expression between MSC- and vehicle-injected ovaries.

CONCLUSIONS:

Intra-ovarian injection of bone marrow-derived MSCs altered gene expression but did not improve ovarian function in aged mares.
口服雌激素  或經皮吸收雌激素對於子宮內膜厚度或IVF懷孕率並無差異

 2018 Dec 5. doi: 10.1007/s10815-018-1380-5. [Epub ahead of print]

Transdermal versus oral estrogen: clinical outcomes in patients undergoing frozen-thawed single blastocyst transfer cycles without GnRHa suppression, a prospective randomized clinical trial.

Abstract

PURPOSE:

To conduct a non-inferiority study to compare the clinical outcomes of transdermal estrogen patch and oral estrogen in patients undergoing frozen-thawed single blastocyst transfer non-donor cycles without GnRHagonist (GnRHa) suppression.

METHODS:

A total of 317 women with irregular menses or anovulatory cycle undergoing frozen-thawed embryo transfer (FET) non-donor cycles without GnRHa suppression were involved in a prospective randomized clinical trial between May 2017 and October 2017. The trial was conducted in an ART and Reproductive Genetics Centre within a private hospital. The unit is designated as a teaching center by the Turkish Ministry of Health. Oral or transdermal estrogen was administered in patients undergoing frozen-thawed single blastocyst transfer. The outcomes of the study were the following: endometrial thickness on the day of progesterone administration, implantation rate, and clinical and viable ongoing pregnancy rates.

RESULTS:

Endometrial thickness and clinical outcomes of oral and transdermal estrogen administration were equally successful (p > 0.05).

CONCLUSION:

No significant difference was found in endometrial thickness on the day of progesterone administration nor in clinical outcomes between transdermal estrogen and oral estrogen in patients undergoing frozen-thawed single blastocyst stage transfer cycles without GnRHa suppression.

2019年1月30日

IVF實驗室內O3, SO2濃度過高對於冷凍胚胎植入懷孕率有不良影響

 2019 Jan 23. doi: 10.1093/humrep/dey386. [Epub ahead of print]

Association between outdoor air pollution during in vitro culture and the outcomes of frozen-thawed embryo transfer.

Wang X1Cai J2,3Liu L2,3Jiang X2Li P2Sha A2Ren J2.

Abstract

STUDY QUESTION:

Does outdoor air pollution differentially affect the outcomes of frozen-thawed embryo transfer (FET) and fresh transfer in IVF treatment?

SUMMARY ANSWER:

Increased SO2 and O3 levels at the site of IVF unit were significantly associated with lower live birth rates following FET but did not affect the contemporary fresh transfer outcomes.

WHAT IS KNOWN ALREADY:

Ambient air pollution has been associated with human infertility and IVF outcomes. However, most of the studies excluded FET cycles.

STUDY DESIGN, SIZE, DURATION:

A retrospective cohort study of 11148 patients contributing to 16290 transfer cycles between January 2013 and December 2016 was carried out.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The average age of the cohort was 31.51 ± 4.48 years and the average BMI was 21.14 ± 2.37 kg/cm2. Inverse distance weighting interpolation was used to estimate the daily ambient exposures to six pollutants (PM2.5, PM10, SO2, NO2, CO, O3) at an IVF clinical site, according to the data from fixed air quality monitoring stations in the city. The exposures of each cycle were presented as average daily concentrations of pollutants from oocyte retrieval to embryo transfer/cryopreservation. Exposures were analyzed in quartiles. A generalized estimating equation was used to evaluate the association between pollutants and IVF outcomes, adjusted for important confounding factors including maternal age, infertility diagnosis, BMI, endometrial status and embryo transfer policy.

MAIN RESULTS AND THE ROLE OF CHANCE:

The clinical pregnancy rate and live birth rate of the cycles was 55.1% (8981/16290) and 47.1% (7672/16290), respectively. Among the included cycles, 4013 patients received 5299 FET cycles, resulting in 2263 live births (42.7% per ET), whereas 9553 patients received 10991 fresh transfer cycles, resulting in 5409 live births (49.2% per ET). SO2 and O3 levels were significantly associated with live birth rates in FET cycles, whereas none of the pollutants were significantly associated with IVF outcomes in contemporary fresh transfer cycles. The FET cycles in the highest quartile of SO2 and O3 exposure had significantly lower live birth rates (adjusted odds ratio (OR) 0.63, 95%CI 0.53-0.74; 0.69, 95% CI 0.58-0.82, respectively) in comparison with those in the lowest quartile. Models involving all transfer cycles and interaction terms (FET×exposures) suggested that FET significantly enhanced the effects of SO2 and O3 exposure on IVF outcomes (P < 0.001). Multi-pollutant models gave consistent results for the association between SO2 and live birth in FET cycles. Accounting for all six pollutants, women in the highest quartile of SO2 still had the lowest live birth rates (OR 0.61, 95%CI 0.47-0.80).

2019年1月29日

Vit D補充可有效改善子宮內膜接受度&懷孕率


 2019 Apr;13(1):18-23. doi: 10.22074/ijfs.2019.5470. Epub 2019 Jan 6.

Effect of Vitamin D Supplementation on Intracytoplasmic Sperm Injection Outcomes: A Randomized Double-Blind Placebo-Controlled Trial.

Abstract

BACKGROUND:

Despite numerous studies indicating an imperative role for reproduction, however, the role of Vitamin D supplementation on outcomes of assisted reproductive techniques remains controversial. This clinical trial was performed to evaluate the effect of Vitamin D supplementation 6 weeks prior to intracytoplasmic sperm injection (ICSI) on fertility indices.

MATERIALS AND METHODS:

The present study was a double-blind clinical trial conducted on infertile women was randomly allocated into two groups: Vitamin D supplementation (42 participants) and placebo (43 participants). Serum Vitamin D was measured before and six to eight weeks after treatment, on the day of ovum pick up. Results were analyzed using SPSS16 and fertility indices were compared between the two groups.

RESULTS:

No significant difference was observed between the intervention and control groups regarding the mean number of oocytes retrieved, percentage mature oocyte, fertilization rate and the rate of good quality embryos (all P>0.05). But, percentages of the individual with suitable endometrium (7-14 mm thickness) were significantly higher in the Vitamin D compared to control group (P=0.011). The rate of chemical (47.6 vs. 25.5%, P=0.013) and clinical pregnancy rate (38.1 vs. 20.9%, P=0.019) were also significantly higher in the Vitamin D compared to control group.

CONCLUSION:

The present study reveals that consuming Vitamin D for 6 weeks prior to ICSI improves quality of endometrium, rate of chemical and clinical pregnancy (Registration Number: IRCT2015111124999N1).
合併letrozole 2.5mg/d & clomid  50mg/d 比單獨使用letrozole 2.5mg/d 對於PCO病患可達更佳誘導排卵效果

 2019 Jan 22. pii: S0015-0282(18)32225-8. doi: 10.1016/j.fertnstert.2018.11.030. [Epub ahead of print]

A randomized controlled trial of combination letrozole and clomiphene citrate or letrozole alone for ovulation induction in women with polycystic ovary syndrome.

Abstract

OBJECTIVE:

To evaluate whether a combination of letrozole and clomiphene citrate (CC) results in higher ovulation rates than letrozole alone in infertile women with polycystic ovary syndrome (PCOS).

DESIGN:

Open-label randomized controlled trial.

SETTING:

Academic medical center using two clinic sites.

PATIENT(S):

Women 18-40 years of age with a diagnosis of infertility and PCOS as defined by the Rotterdam criteria and no other known cause of infertility.

INTERVENTIONS(S):

Participants were randomized in a 1:1 ratio, stratified by age and body mass index, to either 2.5 mg letrozole alone or the combination of 2.5 mg letrozole and 50 mg CC daily on cycle days 3-7 for one treatment cycle.

MAIN OUTCOME MEASURE(S):

Ovulation defined as mid-luteal serum progesterone concentration ≥3 ng/mL.

RESULT(S):

Seventy patients were randomized: 35 to letrozole alone and 35 to letrozole and CC. Results were analyzed according to the intention-to-treat principle. Women who received the combination of letrozole and CC had a statistically higher ovulation rate compared with those who received letrozole alone (27 of 35 women [77%] vs. 15 of 35 women [43%]). There were no serious adverse events or multiple-gestation pregnancies in either group. The side-effects profile was similar in the two treatment groups.

CONCLUSION(S):

The combination of letrozole and CC was associated with a higher ovulation rate compared with letrozole alone in women with infertility and PCOS. Further studies are needed to evaluate the effect on live birth rate.

2019年1月27日

IVF 或ICSI受孕懷孕率無明顯差異
IVF受孕胚胎較ICSI受孕胚胎z分裂較快達到囊胚期

 2019 Jan 9. doi: 10.1007/s10815-018-1358-3. [Epub ahead of print]

In assisted reproduction by IVF or ICSI, the rate at which embryos develop to the blastocyst stage is influenced by the fertilization method used: a split IVF/ICSI study.

Abstract

PURPOSE:

To compare in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) in regard to post-fertilization development and outcome with the purpose of ascertaining the most effective fertilization method for assisted reproduction.

METHODS:

A retrospective cohort study of 136 split IVF/ICSI cycles (where sibling oocytes are fertilized by two different methods using the same sperm sample).

RESULTS:

IVF-derived embryos developed to the blastocyst stage at a significantly faster rate than ICSI-derived embryos. There was no significant difference in fertilization or livebirth rates between the two fertilization methods.

CONCLUSIONS:

For patients with sperm progressive motility ≥ 1.0 × 106/ml (who usually constitute the majority of patients), no significant difference between the two fertilization methods was found in regard to fertilization rate or livebirth rate. Remaining factors influencing choice between the two methods appear to be restricted to convenience, financial considerations and concern with regard to possible perpetuation of genetically linked infertility to future generations.

2019年1月20日

人工受精懷孕率約10-20%
前2次週期之懷孕率約14%
第3次懷孕率降至3.5%


 2018 Jul-Sep;11(3):279-285. doi: 10.4103/jhrs.JHRS_34_18.

An Intrauterine Insemination Audit at Tertiary Care Hospital: A 4½ Years' Retrospective Analysis of 800 Intrauterine Insemination Cycles.

Abstract

BACKGROUND:

There are many variables that may influence the success rates of intrauterine insemination (IUI) treatment. Therefore, a regular audit program is needed for planning effective infertility treatment and improving pregnancy outcomes.

AIMS AND OBJECTIVES:

The main objective of this study was to identify the crucial predicting factors that can influence the IUI success.

MATERIALS AND METHODS:

A retrospective analysis of 800 IUI cycles done from January, 2013 to August, 2017 in 651 couples with various etiologies of infertility. The common etiologies included female factor of ovulatory dysfunction, tubal, endocrinal, male factor, male and female factors combined, and unexplained factors. Ovulation induction was done either by clomiphene citrate (CC) alone or in combination of CC with gonadotropins or pure gonadotropins only. Human chorionic gonadotropin trigger was given when at least one dominant follicle measuring ≥18 mm with an endometrial thickness of >7 mm was obtained. IUI was done post 36 h of trigger. The double-density gradient method was the preferred method of sperm preparation.

RESULTS:

In 800 cycles in corresponding 651 couples, the total outcome was 113 pregnancies (14.1%) per cycle with overall pregnancy rate (PR) per couple of 17.3%. The highest PR was observed in the patient with ovulatory dysfunction (21.2%), followed by patients with combined factor (15.1%) and male factor (14.7%). In the study, a higher PR was achieved in the female ≤25 years (18.9%) P < 0.04 with significant findings with duration of infertility ≤5 years (15.1%) having primary infertility (14.5%) with low body mass index <25 (14.1%). IUI success rate was highest in the first cycle (14.6%) followed by second cycle (14.0%) and third cycle (3.5%).

CONCLUSION:

IUI audit enables the characterization of prognostic factors to achieve improved PR. This study identifies the factors that can predict improved pregnancy outcome in women age ≤25 years and endometrium thickness between 9 and 11 mm. We also recommend IUI as a first line of infertility treatment for couples in low-income setting provided the women age and duration of infertility are acceptably low.

2019年1月17日

成熟MII卵子89% 可經由polyscope見紡錘體
IVM形成之MII卵子僅38%可見紡錘體
具有紡錘體之卵子有較高之囊胚形成率及著床率

 2019 Jan 12. doi: 10.1007/s10815-018-1393-0. [Epub ahead of print]

Egg maturity assessment prior to ICSI prevents premature fertilization of late-maturing oocytes.

Abstract

PROPOSE:

The presence of metaphase II (MII) spindle together with the polar body (PB) indicates completion of oocyte maturation. This study was designed to explore if spindle imaging can be used to optimize timing of intracytoplasmic sperm injection (ICSI).

METHODS:

The study involved 916 oocytes from 234 conventionally stimulated ICSI cycles with an unexpectedly poor ovarian response. All PB-displaying oocytes were subjected to polarized light microscopy (PLM) prior to ICSI. When MII spindle was absent in the majority of oocytes, ICSI was postponed and performed after additional spindle imaging. Fertilization, embryo development, and clinical outcome were evaluated with respect to the observed spindle pattern.

RESULTS:

The visible spindle was absent in 32.64% of PB-displaying oocytes. The late-maturing oocytes extruding PB in vitro were less likely to exhibit a spindle signal than in vivo matured MII oocytes (38.86% vs. 89.84%). When fertilization was postponed, 59.39% of initially spindle-negative oocytes developed detectable MII spindle. Spindled eggs had significantly higher developmental potential, and the presence of the spindle has been identified as an independent measure for predicting the formation of the blastocyst. Embryos derived from spindle-positive oocytes also showed a higher chance to implant and develop to term. Notably, 11 children were conceived by finely timed fertilization of late-maturing oocytes which are normally discarded.

CONCLUSIONS:

The study confirms the prognostic value of spindle imaging and demonstrates that immature oocytes can be clinically utilized and give rise to live births when the timing of ICSI is adjusted to their developmental stage.
卵巢皮質細胞粒線體自體移植入受精卵並無法提高卵子受孕率, 囊胚形成率,染色體正常率‧


 2019 Jan;111(1):86-96. doi: 10.1016/j.fertnstert.2018.09.023. Epub 2018 Nov 24.

Autologous mitochondrial transfer as a complementary technique to intracytoplasmic sperm injection to improve embryo quality in patients undergoing in vitro fertilization-a randomized pilot study.

Abstract

OBJECTIVE:

To study if autologous mitochondrial transfer (AUGMENT) improves outcome in patients with previously failed in vitro fertilization (IVF).

DESIGN:

Randomized, controlled, triple-blind, experimental study.

SETTING:

Private infertility center, Valencian Institute of Infertility (IVI-RMA), Valencia, Spain.

PATIENT(S):

Infertile women ≤42 years of age, body mass index <30 kg/m2, antimüllerian hormone ≥4 pmol/L, >5 million/mL motile sperm, at least one previous IVF with at least five metaphase oocytes (MIIs) collected, and low embryo quality.

INTERVENTIONS(S):

An ovarian cortex biopsy was performed to isolate egg precursor cells to obtain their mitochondria. Sibling MIIs were randomly allocated to AUGMENT (experimental) or intracytoplasmic sperm injection (Control). In AUGMENT, mitochondrial suspension was injected along with the sperm. Viable blastocysts from both groups were biopsied for preimplantation genetic testing for aneuploidy.

MAIN OUTCOME MEASURE(S):

Pregnancy, embryo quality.

RESULT(S):

An interim analysis was conducted. The patients' mean age was 36.3 ± 3.6 years, and they had an average of 2.5 ± 1.5 previous IVF cycles. Two of the 59 enrolled patients spontaneously conceived (one miscarried). Fifty-seven patients had ovarian biopsies and underwent stimulation. Oocyte retrieval was performed in 56 patients (premature ovulation; n = 1). A total of 253 MIIs were inseminated in AUGMENT and 250 in Control; fertilization rates were 62.7 ± 30.0% and 68.7 ± 29.1%, respectively. Statistical differences were observed in day 5 blastocyst formation rates (23.3 ± 32.0% vs. 41.1 ± 36.9%). Neither the euploid rate per biopsied blastocyst (43.8 ± 41.7% vs. 63.8 ± 44.1%) nor the euploid rate per MII (9.8 ± 20.5% vs. 11.9 ± 16.1%) between AUGMENT and Control achieved statistical significance. Moreover, no differences were seen regarding mitochondrial DNA content and relevant morphokinetic variables. Thirty patients were able to undergo embryo transfer. Cumulative live birth rates per transferred embryo were 41.6% in AUGMENT and 41.2% in Control.

CONCLUSION(S):

AUGMENT does not seem to improve prognosis in this population. Therefore, the study has been discontinued.

2019年1月16日

囊胚腔液體DNA全基因放大偵測率(45% of euploid vs  81% of aneuploid)可以做為未來輔助TE PGD

 2019 Jan;111(1):77-85. doi: 10.1016/j.fertnstert.2018.09.016. Epub 2018 Dec 5.

Deoxyribonucleic acid detection in blastocoelic fluid: a new predictor of embryo ploidy and viable pregnancy.

Abstract

OBJECTIVE:

To investigate blastocysts, defined as euploid and aneuploid by trophectoderm (TE) cell analysis, for the presence of DNA in the blastocoelic fluid (BF) detected by whole-genomic amplification (WGA); and to correlate the presence of DNA in BF with the clinical outcome after the transfer of TE-euploid blastocysts.

DESIGN:

Retrospective study.

SETTING:

In vitro fertilization unit.

PATIENT(S):

This study included 91 patients performing preimplantation genetic testing for aneuploidy on TE cells from January 2015 to December 2017. In the case of ET, only single blastocyst transfers were performed.

INTERVENTION(S):

Blastocoelic fluids and TE cells were retrieved from 256 blastocysts before vitrification. All blastocysts were diagnosed by array-comparative genomic hybridization (a-CGH) on TE cells. Amplification and a-CGH of DNA from BFs was performed at a later time after TE biopsy and ET.

MAIN OUTCOME MEASURE(S):

Whole-genomic amplification of BFs, evaluation of the chromosome condition in BFs and TE cells, and correlation of BF results with the clinical outcome of TE-euploid transferred blastocysts.

RESULT(S):

The incidence of amplification after WGA was significantly lower in BFs from TE-euploid blastocysts (n = 32, 45%) when compared with the aneuploid ones (n = 150, 81%), resulting in 182 BFs with successful DNA amplification. When submitted to a-CGH, informative results were obtained from 172 BFs. Comparison of these results with those from the corresponding TE cells gave a ploidy concordance of 93.6% and a mean number of aneuploid events per sample that was higher in BFs than in TE cells (2.0 vs. 1.4, respectively). After the transfer of 53 TE-euploid blastocysts, the clinical pregnancy rate was 77% in the group with BF-failed amplification, and 37% after BF-successful amplification. The same trend was found for the ongoing pregnancy rate (68% vs. 31.5%, respectively).

CONCLUSION(S):

The presence of DNA in BFs detected by WGA is correlated with the blastocyst ploidy condition defined by TE cell biopsy and with the implantation potential of TE-euploid blastocysts. These findings could have a clinical implication for the selection of the most viable embryo for transfer because, after submitting BFs to WGA, priority would be given to TE-euploid blastocysts with BF-failed amplification. Similarly, BF-failed amplification could be an additional selection criterion to prioritize embryos for transfer even in conventional IVF cycles with blastocysts that were vitrified after BF aspiration.

2019年1月12日

完全取不到卵(Empty follicle syndrome, EFS)機率約2.3%   3/4發生於GnRHantagonist的COH療程
大部分EFS病患的卵巢並無明顯衰退 其原因可能在於卵長對於COH之藥物反應異常


 2018 Jul-Sep;11(3):274-278. doi: 10.4103/jhrs.JHRS_61_17.

Empty Follicle Syndrome: A Challenge to Physician.

Abstract

BACKGROUND:

Empty follicle syndrome (EFS) is a condition in which no oocytes are retrieved from normally growing ovarian follicles after ovarian stimulation. It is a rare and frustrating condition of obscure etiology.

OBJECTIVE:

The objective of this study was to estimate the incidence of EFS and study factors related to it.

DESIGN:

This was a retrospective study.

SETTING:

This study was conducted in hospital-based research center.

METHODS:

In 1968 in vitro fertilization cycles from January 2010 to August 2016 were studied. Agonist, antagonist, and miniflare protocols were used for the stimulation.

RESULTS:

The incidence of EFS is 2.38% (47/1968 cycles). Antagonist protocol group (76.59%, n = 36) had highest incidence of EFS (6.69%). Literature on EFS depicts decreased ovarian reserve (DOR) as the main cause, but only 4.25% of patients had DOR in our study. Interestingly, polycystic ovary syndrome and unexplained infertility were found in 31.9% of the cases. Serum anti-Müllerian hormone (AMH) levels (mean ± standard deviation [SD]) were 4.47 ± 3.54 ng/ml, and antral follicle count (AFC) was 15.30 ± 8.07 (mean ± SD) emphasizing that diminished ovarian reserve is not the main factor for EFS. All patients (n = 95) who underwent ovum pickup on day when any patient had EFS were taken as control. Patients with EFS were compared with controls. A statistically significant difference was not observed in serum AMH (P = 0.38) and AFC (P = 0.52).

CONCLUSION:

EFS is an uncommon event. Antagonist cycles have higher chances of empty follicle at ovum pickup. Looking at the profile of patients in this study, we conclude that EFS is not a manifestation of DOR.
超低2% CO2濃度 vs 5%CO2對胚胎著床懷孕並無明顯助益

 2018 Dec 20. doi: 10.1093/humrep/dey370. [Epub ahead of print]

Influence of ultra-low oxygen (2%) tension on in-vitro human embryo development.

Abstract

STUDY QUESTION:

Is a reduction in the oxygen tension from 5 to 2% during extended culture from Day 3 onwards beneficial for human blastocyst development in vitro?

SUMMARY ANSWER:

A reduction in oxygen concentration from 5 to 2% O2 after Day 3 did not improve embryo development, quality and utilization rate.

WHAT IS KNOWN ALREADY:

The human embryo leaves the fallopian tube to reach the uterine cavity around Day 3-4 post-ovulation. As the oxygen concentration ranges from 5 to 7% in the fallopian tube and decreases to 2% in the uterus, reducing the oxygen tension during extended culture from Day 3 onwards seems more physiological. We aim to mimic the in-vivo environment during in-vitro embryo culture. Therefore, we compared the effect of extended culture performed at 5% (control arm) or 2% oxygen (O2; study arm) tension on blastocyst formation and quality.

STUDY DESIGN, SIZE, DURATION:

Between December 2016 and September 2017, in two prospective studies, sibling embryos were randomized on Day 3 to either 5% O2 (control) or 2% O2 (study) for extended culture. In the control arms of both studies 1 and 2, the dishes with blastocyst medium were pre-equilibrated overnight in 5% O2, 6% CO2 and 89% N2 at 37°C. In the 2% study groups, the overnight pre-equilibration of blastocyst media was performed in either 2% O2 (study 1, 99 cycles) or 5% O2 (study 2, 126 cycles). The latter provides a gradual transition from 5 to 2% O2 environment for the study arm.

PARTICIPANTS/MATERIALS, SETTINGS, METHODS:

Embryo culture until Day 3 was always performed in 5% O2; if at least four embryos of moderate to excellent quality were obtained on Day 3, the sibling embryos were randomized to either 5% O2 or 2% O2 for extended culture. The endpoints were embryo development and quality on Day 5/6 and the utilization rate (embryos transferred and cryopreserved). Statistical analysis was performed using the chi-square test, a P-value of <0.05 was considered significantly different.

MAIN RESULTS AND THE ROLE OF CHANCE:

In study 1, 811 embryos were randomized on Day 3: 405 to the 2% O2 and 406 to the 5% O2 condition. No differences were observed in the blastulation rate (68.6 versus 71.9%; P = 0.319) and the proportion of good quality blastocysts on Day 5 (55.8 versus 55.2%; P = 0.888), nor in the utilization rate (53.1 versus 53.2%; P = 1.000). In study 2, 1144 embryos were randomized: 572 in each arm. Similarly, no significant difference was demonstrated in terms of the blastulation rate (63.6 versus 64.7%; P = 0.758), the proportion of good quality blastocysts (46.9 versus 48.8%; P = 0.554) or the utilization rate (49.8 versus 48.1%; P = 0.953).