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Can Fast Growing Embryos Determine Sex of Baby With Icsi

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Changes in sex ratio from fertilization to birth in assisted-reproductive-handling cycles

Reproductive Biology and Endocrinology volume 12, Article number:56 (2014) Cite this article

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Abstract

Groundwork

In Western gender-neutral countries, the sex ratio at birth is estimated to exist approximately 1.06. This ratio is lower than the estimated sex ratio at fertilization which ranges from 1.07 to 1.70 depending on the figures of sex ratio at nativity and differential embryo/fetal mortality rates taken into account to perform these estimations. Also, little is known most the sex ratio at implantation in natural and assisted-reproduction-handling (ART) cycles. In this bioessay, we aim to gauge the sex activity ratio at fertilization and implantation using information from embryos generated by standard in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in preimplantation genetic diagnosis cycles. Thereafter, we compare sex ratios at implantation and birth in cleavage- and blastocyst-stage-transfer cycles to propose molecular mechanisms accounting for differences in post-implantation male and female mortality and thereby variations in sexual practice ratios at birth in Art cycles.

Methods

A literature review based on publications upwardly to December 2013 identified by PubMed database searches.

Results

Sexual practice ratio at both fertilization and implantation is estimated to be between 1.29 and ane.50 in IVF cycles and i.07 in ICSI cycles. Compared with the estimated sex ratio at implantation, sex ratio at nascency is lower in IVF cycles (1.03 after cleavage-stage transfer and 1.25 afterwards blastocyst-stage transfer) but similar and shut to unity in ICSI cycles (0.95 subsequently cleavage-stage transfer and 1.04 afterward blastocyst-stage transfer).

Conclusions

In-vitro-civilisation-induced precocious Ten-chromosome inactivation together with ICSI-induced decrease in number of trophectoderm cells in female person blastocysts may account for preferential female person bloodshed at early mail-implantation stages and thereby variations in sex activity ratios at birth in Art cycles.

Background

In Western gender-neutral countries, the sex ratio at nativity is estimated to be ≈ i.06 (for a review, see Hesketh and Xing [i]). This ratio is lower than the estimated sex ratio at fertilization which ranges from 1.07 to 1.70 depending on the figures of sex activity ratio at birth and differential embryo/fetal mortality rates taken into business relationship to perform these estimations (for a review, see Pergament et al. [ii]). Likewise, lilliputian is known about the sex ratio at implantation in natural and assisted-reproduction-treatment (Art) cycles. Still, implantation is a disquisitional process that many embryos do not become through and, therefore, this outcome should be considered equally important every bit fertilization or birth when analyzing changes in sex ratio through dissimilar stages of embryo/fetus development.

Fortunately, data from embryos generated by standard in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) in preimplantation genetic diagnosis (PGD) cycles may be used to guess not only the sex activity ratio at fertilization (primary sex ratio) in a more authentic way than previous studies (for a review, encounter Pergament et al. [2]) but besides the still-unknown sexual activity ratio at implantation. In this bioessay, nosotros use data from IVF and ICSI embryos analyzed in PGD cycles as a proxy for estimating the sex ratio at both fertilization and implantation. Thereafter, nosotros compare the sex ratios at implantation and birth (secondary sex ratio) in cleavage- and blastocyst-stage-transfer cycles to propose molecular mechanisms bookkeeping for differences in mail-implantation male person and female mortality and thereby variations in sex ratios at birth in ART cycles.

Methods

A literature review based on publications up to Dec 2013 identified by PubMed database searches using the following fundamental words: sexual activity ratio, preimplantation genetic diagnosis, cleavage-phase transfer, blastocyst-stage transfer, IVF, ICSI, biochemical pregnancy, fetal bloodshed, Ten-chromosome inactivation (XCI). This literature search retrieved a limited number of studies and put in evidence the absence of well-designed controlled randomized trials analyzing the concomitant event of both insemination technique (IVF versus ICSI) and developmental stage at the time of embryo biopsy/transfer (cleavage versus blastocyst stage) on sex ratio of embryos/newborns. Notably, simply one article [3] compiling the chromosomal sex of 117 IVF 4- to 8-cell embryos from PGD cycles was identified in our literature search. This is not surprising because during the early nineties, before the advent of ICSI, PGD applied science was in its infancy, and patients and PGD laboratories were limited. For example, the article by Griffin et al. [three] is a compendium of 27 PGD cycles performed in 4 separated serial at the Hammersmith Hospital, London, over a 2-twelvemonth period in 18 couples at risk of transmitting X-linked recessive disorders. Oocytes and embryos were cultured in Earle's Balanced Salt Solution (EBSS) supplemented with x% rut-inactivated maternal serum and biopsied blastomeres analyzed by fluorescent in situ hybridization (FISH). Consequently, estimates of sex ratios at fertilization and implantation based on data shown in Tabular array i should be considered as relative values, non as absolute and precise figures. Estimates of sex ratios at birth from Table 2 are based on larger sample sizes and therefore are more robust than estimates of sexual activity ratios at fertilization and implantation in IVF cycles. In any case, comparisons between groups in this bioessay should be performed in a qualitative way, not in a quantitative/statistical mode using meta-assay or statistical inference methods.

Table one Sex activity ratio (XY/XX) of genetically diagnosed preimplantation embryos according to the method of fertilization practical and embryo developmental phase

Total size tabular array

Table two Sex ratio (XY/XX) at nativity of singleton deliveries co-ordinate to the method of fertilization applied and the mean solar day of embryo transfer

Total size tabular array

Fertilization and preimplantation stages

It has been reported that human ejaculated spermatozoa brandish a normal Y:10 ratio that does non differ from the Mendelian ratio [4–half dozen]. Nonetheless, Table 1 shows that genetically diagnosed 4- to viii-prison cell IVF embryos exhibit sexual activity ratios between 1.29 and one.fifty. These figures contrast with the sex activity ratio closer to unity displayed by ICSI viii-prison cell embryos (1.09). Differences in sexual practice ratios between IVF and ICSI embryos may be due to the fact that ICSI bypasses the zona pellucida and thereby any putative role information technology may have in selecting 10- or Y-bearing spermatozoa (see below). Nevertheless, we should note that the sexual practice ratio of cleavage-phase ICSI embryos is biased towards females when performing sperm selection for normal shaped nuclei, especially under loftier magnification (0.53, 112/210, in selected sperm injection versus 0.86, 96/112, in standard ICSI) [7] or when using the swim-up technique for preparation of spermatozoa from heavy smokers (0.47, 22/47, in heavy smokers; 0.95, 21/22, in slight-to-moderate smokers; and 1.13, lxxx/71, in non-smokers) [4].

There are several mechanisms that may account for the relatively elevated sex ratio plant in IVF 4- to 8-cell embryos: (i) IVF male person embryos may have a developmental reward over female embryos later on fertilization; (two) the sperm preparation technique (either swim-upwards or three-layer discontinuous Percoll density slope centrifugation) used in IVF may increase the proportion of Y-bearing spermatozoa; (iii) the molecular limerick of the zona pellucida may render oocytes more than susceptible to fertilization by Y-bearing spermatozoa; and/or (iv) Y-bearing spermatozoa may have college fertilization ability.

Previous studies have reported that the sex activity ratio of preimplantation bovine embryos may be skewed towards males (i.east., preferential loss of female embryos) by manipulating the culture system including addition of glucose [8, 9] and glucosamine [ten]. In contrast, in humans the possibility that IVF male embryos take a developmental reward over female embryos subsequently fertilization is not supported by data on preimplantation embryo development. Firstly, information technology is known that ≈ x% of all human IVF (or ICSI) embryos undergo early developmental abort [11]. This arrest likely occurs to prevent further development of sure chromosomally aberrant embryos and/or embryos that fail to activate embryonic genome around the 4- to 8-cell stage [12]. Of annotation, this early developmental block does not seem to depend on sex of embryos. Actually, a non-pregnant sex ratio of one.05 (86/82) has been evidenced in arrested embryos that do not laissez passer the eight-jail cell stage after IVF [thirteen]. And secondly, as shown in Table 1, the sex ratio of both ICSI 8-cell embryos (one.09) and day-5 blastocysts (0.98) is close to unity suggesting that further developmental arrest afterward the 8-jail cell stage is not sexual activity dependent. Indeed, the developmental potential of ICSI eight-cell embryos towards the early, total or hatched-blastocyst stage on day 5 is like between male person (23.one%, 110/475) and female (21.six%, 88/408) embryos [14]. Consequently, we tin can assume that the sex ratio at both fertilization and implantation is between 1.29 and one.50 in IVF cycles (the sex ratio of cleavage-stage embryos) and one.07, 1185/1110, in ICSI cycles (this estimate results from combining sex ratios of cleavage-stage and blastocyst-stage ICSI embryos; come across Table 1). We should notation that the estimates of sexual practice ratios at fertilization and implantation in IVF cycles are not robust due to the relative minor number of embryos analyzed (n = 117) and the bias that may be introduced by inferring sex activity ratios at fertilization and implantation from data of cleavage-phase embryos. We should bear in heed the work by Fiala [fifteen] pointing out that the sex ratio of surviving offspring cannot correctly be used to estimate the primary sex activity ratio considering of the potential sex differential of mortality. Unfortunately, obvious upstanding reasons forbid assessing straight sex activity ratios at fertilization and implantation in human beings.

The second option, i.e., the sperm grooming technique used in IVF may increase the proportion of Y-bearing spermatozoa, can exist also rejected. In fact, information technology has been shown that the swim-up technique does non selectively enrich either X- or Y-bearing spermatozoa [16–18]. Equally mentioned higher up, only in heavy smoking men swim-up technique may increase the proportion of 10-bearing (instead of Y-bearing) spermatozoa resulting in higher incidence of female person embryos after ICSI [4]. Moreover, it is known that the three-layer discontinuous Percoll density slope selects spermatozoa with meliorate movement characteristics, more hyperactivation, and improved longevity compared with directly swim-upwardly [19]. However, studies aimed to ascertain the efficiency of discontinuous Percoll density gradient centrifugation in sperm sorting show either no significant effect on X:Y ratio of spermatozoa or even an enrichment of X-bearing spermatozoa that seems to be insufficient for clinical use in pre-conceptional sex selection (for references, see Lin et al. [xx]).

The third and quaternary possibilities, i.e., oocytes may be more than susceptible to fertilization by Y-begetting spermatozoa and/or Y-bearing spermatozoa may have college fertilization power, are more probable to be truthful. Indeed, recent evidence strongly suggests that oocytes during a disquisitional time in folliculogenesis may change the molecular composition of the zona pellucida, e.g., a subtle variation in a sperm-bounden carbohydrate on the zona-pellucida proteins induced by high levels of follicular-fluid testosterone. This molecular change may render oocytes more than susceptible to fertilization by Y-bearing spermatozoa (for a review, see Grant and Chamley [21]). In improver, there are convincing data on the presence of distorter genes, expressed and translated after meiosis in circular spermatids and spermatozoa, able to skew the sex activity ratio by affecting spermatid maturation and fertilizing ability of either X- or Y-bearing spermatozoa (for a review, see Ellis et al. [22]). This fact suggests that homo spermatids and spermatozoa may "intrinsically" limited distorter genes favoring spermatid maturation and fertilizing ability of Y-bearing spermatozoa.

Implantation and early postal service-implantation stages earlier pregnancy becomes clinically recognized

Table 2 shows data retrieved from United States [23] and Australia and New Zealand [24] assisted reproductive databases. We selected these studies considering they focused their analyses on big samples of Fine art singleton deliveries [23] or births resulting from single embryo transfers [24]. Noteworthy, Dean et al. [24] included in the adding and analysis of sex ratio at birth simply one baby from each set of multiple births. This strategy eliminated the potential bias that monozygotic twins may introduce in the calculation of sex activity ratio at nascency. These data point that extended embryo civilization to the blastocyst phase is associated with college sex ratio at birth compared with shorter embryo culture to the 4- or 8-cell phase (1.25 versus one.03 in IVF cycles and 1.04 versus 0.95 in ICSI cycles). Moreover, sex activity ratio at nascency is lower in ICSI cycles than in IVF cycles after cleavage- (0.95 versus 1.03) and blastocyst-stage (1.04 versus 1.25) transfer. These results are qualitatively consistent with a previous systematic review and meta-analysis [25] and previous studies [26–29] not included in Table ii because they did not provide the appropriate data and/or did not control for the potential bias associated with monozygotic twining.

The higher sexual activity ratio at birth evidenced after blastocyst-stage transfer is not probable a consequence of embryo grading systems that prioritize male embryos for transfer as suggested by Alfarawati et al. [thirty]. Indeed, despite an early report [31] reported that male IVF human preimplantation embryos brandish increased number of cells and metabolic activity than female embryos, strong show shows that man preimplantation male embryos do not cleave faster [32–34], exhibit better morphology [32] and/or accept college developmental potential [13, 14] than female person embryos. This fact suggests that the human endometrium does not select the sex of implanting embryos as previously hypothesized past Krackow [35] and Tarín et al. [36], or evidenced in mouse embryos displaying sexual activity-dimorphic developmental rates [37, 38]. Instead, we advise that the higher secondary sexual activity ratio found after blastocyst-stage transfer may be due to preferential female mortality at early mail-implantation stages induced, at to the lowest degree in role, by abnormal inactivation of ane of the two Ten-chromosomes (machinery of dosage compensation).

XCI in the mouse model

Two recent reviews past Lee and Bartolomei [39] and Lessing et al. [xl] show that in the mouse XCI begins during the first meiotic prophase of spermatogenesis. After completion of meiosis, the Ten-chromosome does non completely reactivate. Indeed, 85% of X-linked genes remain suppressed through spermiogenesis. Thus, the paternal Ten-chromosome is passed onto the next generation in a partially inactivated state. At the two-cell stage, transcription of repetitive elements on the paternal X-chromosome is already suppressed, but transcription of X-linked coding genes is active. At the 8-16-jail cell stage (morula phase), the silencing of paternal coding genes is initiated, and is completed at the blastocyst stage or later. Gene silencing absolutely requires cis accumulation of a long not-coding Xist RNA that coats the 10-chromosome and binds Polycomb repressive complex 2 (PRC2), the epigenetic circuitous responsible for trimethylation of histone H3 on lysine 27 (H3K27me3), a repressive epigenetic marking that leads to further silencing of the paternal 10-chromosome. This is not the case for silencing repetitive elements on the paternal 10-chromosome. Past the two-cell stage, although Xist RNA is present, repetitive elements are silenced in a Xist independent manner. The maternal X-chromosome is protected from inactivation through expression of Xist'south antisense repressor, Tsix.

As paternal XCI is heritable through mitosis, the paternal 10-chromosome remains inactivated in both the trophectoderm and the primitive endoderm (hypoblast). In dissimilarity, in the inner prison cell mass (ICM), the paternal Ten-chromosome undergoes reactivation. We should comport in mind that the trophectoderm gives ascension to the fetal portion of the placenta; the archaic endoderm originates the parietal endoderm that contributes to the parietal yolk sac, and the visceral endoderm that contributes to the visceral and intraplacental yolk sacs; and the ICM gives ascension to the epiblast lineage that develops into the embryo proper and the extra-embryonic mesoderm that forms the allantois and the mesodermal components of the visceral yolk sac, amnion and chorion (for reviews, see Hemberger [41] and Gasperowicz and Natale [42]).

Starting from the menstruum shortly after implantation, Ten-chromosomes in the epiblast experience random inactivation, i.e., the maternal X-chromosome is inactive in some cells whereas the paternal X-chromosome is inactive in other cells. Paternal X-chromosome reactivation also occurs in primordial germ cells in preparation for equal segregation during meiosis (for reviews, see Lee and Bartolomei [39] and Lessing et al. [twoscore]).

XCI in humans

Dissimilar in mice, XIST expression is not imprinted in humans. XIST expression is detected from the iv- to 8-cell stage at the onset of genomic activation [43]. Both ICM and trophectoderm show similar XIST RNA accumulation in their cells. However, XIST upregulation does not effect in firsthand onset of chromosome-wide XCI even in tardily (day-vii) blastocysts [44]. Recently, Teklenburg et al. [45] using an in-vitro model for human implantation observed that implanting day-8 female embryos had distinct H3K27me3 foci (presumably on the inactive X-chromosome) localized to the trophectoderm lineages and to lesser extend the hypoblast lineages, but non in epiblast cells. These findings indicate that in the majority of the cells of human embryos, silencing of the X-chromosome may occur later on the embryo has implanted. This conclusion contradicts data from another study reporting that XIST RNA accumulation is associated with transcriptional silencing of the XIST-coated chromosomal region every bit early on as the morula and the blastocyst stage [43]. Discrepancies between studies may be explained by differences in efficiency of the immunofluorescence/FISH technique in detecting biallelic RNA signals and/or the employ of different culture conditions (cited by Okamoto et al. [44]).

Early studies suggested the occurrence of paternal XCI in the fetal side of placentae. These studies analyzed the expression pattern of single X-linked genes. However, other studies using more robust analyses of multiple allele-specific gene expression along the X-chromosome back up the notion that XCI in human placentae is random (for a review, come across Lee and Bartolomei [39]). Similarly, information technology is more often than not accepted that X-chromosomes in the ICM lineage undergo random inactivation (for a review, see Migeon [46]). Nonetheless, a recent written report has shown that the bell-shaped distribution (centered effectually 50%) of X-inactivation patterns in big populations of normal women fits better a three-allele model of genetically influenced XCI than models of completely random inactivation [47].

We should emphasize that not all the 10-linked genes are silenced at X-inactivation. In humans, more than xv% of genes carried on the X-chromosome announced to escape inactivation (for a review, see Brownish and Greally [48]). Consequently, differences in cistron dosage may explain differences betwixt men and women in developmental programming and disease susceptibility and beliefs (for a review, encounter Aiken and Ozanne [49]). Moreover, although XCI in homo epiblast, hypoblast and trophectoderm cells probable occurs during/later on implantation (see higher up), the silencing procedure may be disrupted during preimplantation stages past any cistron that interferes with DNA methylation, histone deacetylation or chromatin modifications. The resulting increased or decreased X-linked cistron expression may prevent embryos to either implant or develop normally after implantation (for reviews, see Hemberger [50] and Schulz and Heard [51]). We propose that extended exposure of preimplantation female embryos to suboptimal (non-physiological) culture systems may be "one" of these factors.

Precocious XCI in homo embryonic stem cells (hESCs)

It has been reported [52] that the conventional method of hESCs (pluripotent cell types derived from the ICM of human blastocysts) derivation and maintenance under atmospheric O2 conditions (≈xx% Otwo) too as exposure to other cellular stresses such as harsh freeze-thaw cycles, inhibition of the proteosome, HSP90, gamma-glutamylcysteine synthetase, and treatment with organic peroxide, induces precocious random XCI prior to cellular differentiation. This precocious XCI is associated with either XIST expression in most or all cells, or the absence of XIST expression and failure to reactive XIST expression upon differentiation. This response differs from that found nether v% O2 concentration. In this case, the precocious random XCI in hESCs is prevented, being both 10-chromosomes agile. Furthermore, hESCs exhibit no XIST expression and retain the power to activate XIST gene expression upon differentiation.

It is worth mentioning that nowadays in many IVF laboratories gametes and embryos are withal exposed to non-physiological culture systems including atmospheric O2 concentrations despite data from a systematic review and meta-analysis [53] suggest that embryo culture to the blastocyst stage under depression-oxygen concentration (≈five%) versus high-oxygen atmospheric concentration yields higher live nativity rates. Thus, information technology tin can exist inferred that embryos cultured to the blastocyst phase (embryo transfer on day 5 or vi) nether not-physiological environments including atmospheric O2 concentrations are more susceptible to undergo epigenetic changes than embryos cultured for shorter periods of fourth dimension (embryo transfer on ≤ day 3). Like hESCs, these epigenetic changes may interfere with the normal process of XIST expression and XCI in female embryos. Importantly, in-vitro-produced preimplantation bovine embryos display college levels of XIST expression than their in-vivo counterparts, suggesting that in-vitro-culture conditions induce premature XCI [54].

Nosotros should stress that in the subgroup of hESC lines displaying precocious XCI and XIST expression in most or all cells when exposed to atmospheric O2 conditions [52], XIST expression was unstable and subject to stable epigenetic silencing by Deoxyribonucleic acid methylation. The resulting inhibition of XIST expression reactivated a portion of X-linked alleles on the inactive X-chromosome (12% of 10-linked promoter CpG islands became hypomethylated) [55]. Such a reactivation resulted in over-expression of 10-linked genes, event that if took place in implanting female blastocysts may produce astringent abnormalities in embryonic and extra-embryonic (trophoblast) tissues and early embryonic death (for a review, see Schulz and Heard [51]).

Data supporting and refuting the hypothesis of occurrence of precocious XCI in human female embryos

The hypothesis of occurrence of precocious XCI in female person embryos exposed for extended periods of time to non-physiological civilisation systems is questioned by (i) the absence of significant differences in miscarriage percentage per couple later on cleavage- (eight.0%, 86/1069) and blastocyst-phase (nine.2%, 97/1058) transfer; and (ii) the college live-birth percentage per couple subsequently blastocyst-phase transfer (38.9%, 292/751, versus 31.2%, 237/759, later cleavage-stage transfer) (for a systematic review and meta-analysis, meet Glujovsky et al. [56]). Every bit a affair of fact, nosotros should look college miscarriage percentages and lower live-birth percentages afterwards blastocyst-stage transfer if a given pct of female embryos undergoes precocious XCI. However, it is generally thought that extended culture selects those embryos that have proven ability to survive and develop to an avant-garde stage in vitro [although a wide range of blastulation rates has been reported (from 28% to 97%), on average just 46.8% of embryos achieve the blastocyst stage (for a systematic review and meta-assay, meet Glujovsky et al. [56])]. This fact together with the presence of an uterine environment that likely is more than synchronized compared with cleavage-stage transfers ([57]; for a review, see Bourgain and Devroey [58]) may contribute to the like miscarriage rates and higher alive-birth percentages reported after blastocyst-phase transfer compared with cleavage-stage transfer.

In addition, the incidence of female losses (presumably caused past precocious XCI) is likely higher at early on stages of pregnancy before women are aware that they are meaning than after pregnancy has been clinically recognized (note that early pregnancy losses are not taken into business relationship when analyzing miscarriage percentages). In this context, we should mention that blastocyst-stage transfer is associated with college per centum of biochemical pregnancy losses per embryo transfer (14.1%, 108/767) [59] than cleavage-stage transfer (8.2%, 154/1888) [sixty].

Late mail service-implantation stages afterward pregnancy becomes clinically recognized

Shortly after pregnancy becomes clinically recognized, females keep displaying a developmental disadvantage compared with males. This disadvantage subsequently vanishes as gestational age increases. In particular, by combining the information reported by Eiben et al. [61] and Yusuf and Naeem [62], sex ratios of chromosomally normal abortions increase from 0.46, 67/147, at v–9 weeks of pregnancy to 0.79, 137/173, at 10–13 weeks and 1.02, 269/263, at ≥ 13 weeks. A concomitant increment in natural choice against males with gestational historic period is also evidenced in chorionic villus sampling and amniocentesis material from control meaning women. In these ongoing pregnancies, sex ratios significantly subtract from 1.28, 791/618, at < sixteen weeks of pregnancy to 1.06, 25433/23994, at ≥ 16 weeks [63]. We should bear in listen that human males and females develop at unlike rates in uterus (and postnatally until the postpubertal stage). Thus, male fetuses take a greater effective exposure to a given insult than female fetuses that undergo fewer cell cycles during the same period of exposure (for a review, see Aiken and Ozanne [49]).

Birth

Tabular array 2 shows that, compared with the estimated sex activity ratio at implantation (1.29 to i.50 in IVF cycles and 1.07 in ICSI cycles), the sex ratio at nativity is lower in IVF cycles (1.03 and 1.25 afterwards cleavage- and blastocyst-stage transfer, respectively) but like and closer to unity in ICSI cycles (0.95 and i.04 later on cleavage- and blastocyst-stage transfer, respectively). Note that we should expect lower sex ratios at birth than at implantation if male mortality during pregnancy surpasses female person losses. On the contrary, nosotros should expect sexual activity ratios at birth similar to or even college than sex ratios at implantation if female mortality is comparable or exceeds male bloodshed.

Nosotros should stress that sex ratios at nascency are closer to sexual practice ratios at implantation after blastocyst-stage-transfer than after cleavage-phase-transfer. This fact is in consonance with the hypothesis of occurrence of precocious XCI in female person embryos cultured in vitro to the blastocyst stage. Also, sex ratios at nascence are nearer to sex ratios at implantation in ICSI than in IVF cycles. In this context, we should mention the written report by Dumoulin et al. [64] reporting decreased number of trophectoderm cells in ICSI female person blastocysts compared with ICSI male blastocysts (this effect was not observed in IVF blastocysts). As the trophectoderm lineage gives ascension to the fetal portion of the placenta, ICSI female person blastocysts may exhibit higher incidence of abnormal trophoblast function and decreased potential for implantation and further evolution compared with ICSI male blastocysts.

Final remarks

Data from genetically diagnosed preimplantation embryos suggest that the sex activity ratio at both fertilization and implantation is between ane.29 and 1.50 in IVF cycles and 1.07 in ICSI cycles. Embryo exposure to culture media for extended periods of fourth dimension to the blastocyst stage under non-physiological conditions (e.chiliad., under atmospheric O2 conditions) may induce precocious XCI in female person embryos. Such a precocious XCI together with ICSI-induced subtract in number of trophectoderm cells in female blastocysts may account for preferential female person mortality at early on mail-implantation stages and thereby variations in sex ratios at nativity in Art cycles. In item, in IVF cycles the early on developmental disadvantage of females would exist surpassed by the higher mortality rates of males after in pregnancy resulting in lower sex ratios at birth than at implantation. In contrast, in ICSI cycles early female person mortality would exist comparable to subsequently male mortality affording similar sex ratios at nascence and implantation. Blastocyst transfer in both IVF and ICSI cycles would exist associated with higher mail service-implantation female bloodshed than cleavage-phase transfer. Consequently, sex ratios at birth would be closer to sex ratios at implantation after blastocyst transfer than after cleavage-phase transfer.

The hypothesis of precocious XCI may be extended to natural cycles to explain, at to the lowest degree in function, some biases of sex activity ratio at birth observed in human populations/families (for reviews, come across James [65, 66]). In particular, disturbances of XCI may be induced past biological (due east.g., gametes from reproductive-erstwhile women/men and pre- or mail-ovulation/ejaculation anile gametes) or environmental (east.grand., maternal exposure to nutritional deficits/excesses, concrete/psychological/social stresses, medications, social drugs, radiations, environmental pollutants and chemotherapy agents) factors. Certainly, this is a research area that needs further attending.

Abbreviations

5mC:

Fifth carbon of the cytosine base of operations

Fine art:

Assisted reproduction treatment

EBSS:

Earle's balanced salt solution

FISH:

Fluorescent in situ hybridization

H3K27me3:

Histone H3 on lysine 27

hESCs:

Human embryonic stalk cells

ICSI:

Intracytoplasmic sperm injection

IVF:

In-vitro fertilization

PRC2:

Polycomb repressive complex 2

XCI:

X-chromosome inactivation.

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Affiliations

  1. Department of Functional Biology and Concrete Anthropology, Faculty of Biological Sciences, University of Valencia, 46100, Burjassot, Valencia, Spain

    Juan J Tarín

  2. Department of Genetics, Faculty of Biological Sciences, University of Valencia, Burjassot,and Research Unit-INCLIVA, Infirmary Clínico de Valencia, Valencia 46100;, 46010, Valencia, Espana

    Miguel A García-Pérez

  3. Department of Physiology, Faculty of Medicine, University of Valencia, and Research Unit-INCLIVA, Hospital Clínico de Valencia, Valencia 46010;, 46010, Valencia, Spain

    Carlos Hermenegildo

  4. Section of Pediatrics, Obstetrics and Gynecology, Faculty of Medicine, Academy of Valencia, and Service of Obstetrics and Gynecology, University Hospital Dr. Peset, Valencia 46010;, 46017, Valencia, Kingdom of spain

    Antonio Cano

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Correspondence to Juan J Tarín.

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The authors declare that they have no competing interests.

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JJT was involved in the formulation and design of the study, the acquisition, analysis and estimation of data and drafting of the commodity. MAGP, CH and Air-conditioning were involved in the assay and estimation of information, and revising the article critically for of import intellectual content. All authors read and approved the terminal manuscript.

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Tarín, J.J., García-Pérez, K.A., Hermenegildo, C. et al. Changes in sex ratio from fertilization to birth in assisted-reproductive-handling cycles. Reprod Biol Endocrinol 12, 56 (2014). https://doi.org/10.1186/1477-7827-12-56

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Keywords

  • Blastocyst-stage transfer
  • Cleavage-stage transfer
  • Preimplantation embryo development
  • Sex ratio
  • X-chromosome inactivation

Can Fast Growing Embryos Determine Sex of Baby With Icsi

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