Sex selection and non-invasive prenatal testing: A review of current practices, evidence, and ethical issues.

Non-invasive prenatal testing (NIPT) can determine the sex of the fetus very accurately and very early in gestation. There are concerns that the ease, timing, and accuracy of NIPT sex determination will facilitate sex-selective termination of pregnancy (TOP). Here, we review current practices, the evidence for a link between NIPT and sex-selective TOP, and associated ethical issues. Sex-selective TOP, usually motivated by son preference, has had serious demographic consequences in countries such as India and China. Currently, ultrasound is the primary method by which parents determine the sex of the fetus. The diffusion of ultrasound technology has had a direct impact on the rates of sex-selective TOP. Although NIPT is currently more costly, it is feasible that increased uptake of this technology could have a similar effect. Partly because NIPT is a relatively recent development in prenatal screening, there is little data on the impact of NIPT on sex selection practices. Evidence that NIPT is playing a role in sex-selective TOP remains largely anecdotal. Further research is required to assess and quantify TOP resulting from NIPT sex determination. The use of these technologies for sex selection raises a number of ethical issues, in addition to practical demographic consequences.

On the estimation of female births missing due to prenatal sex selection.

This research note is prompted by a paper by Kashyap (Is prenatal sex selection associated with lower female child mortality? Population Studies 73(1): 57-78). Kashyap's paper, which provides 40 original estimates of missing female births, relies on an alternative definition of missing female births, leading to estimates of about half the magnitude of other estimates. There appears, therefore, a real need to take stock of the concept of missing female births widely used by statisticians around the world for assessing the demographic consequences of prenatal sex selection. This research note starts with a brief review of the history of the concept and the difference between Amartya Sen's original method and the alternative method found elsewhere to compute missing female births. We then put forward three different arguments (deterministic and probabilistic approaches, and consistency analysis) in support of the original computation procedure based on the number of observed male births and the expected sex ratio at birth.

Sex selection in late Iberian infant burials: Integrating evidence from morphological and genetic data.

OBJECTIVE: The aim of this study was to analyze the infant burials found inside Iberian homes in relation to a possible case of sex selection. METHODS: The study included the remains of 11 infant individuals buried under the 10 houses excavated in the late Iberian village of Camp de les Lloses (Tona, Barcelona, Spain). Sex was determined using genetic analysis. RESULTS: Our results showed that almost all the burials were females. However, the age interval of death was wide enough to weaken the premise of infanticide, and the burials probably represent cases of natural death. DISCUSSION: Infanticide in its different forms has long been argued as an explanation for the infant remains found throughout various burial sites. Many authors thought that infanticide, mainly femicide, was the main method of population control in ancient times. However, there is no anthropological evidence (age distribution and sex analyzed genetically) to support the intentional killing of females in this or in other cases. We hypothesized that there was a positive selection for females to be buried inside the houses, probably related to their benefactor roles.

Is prenatal sex selection associated with lower female child mortality?

I examine whether prenatal sex selection has substituted postnatal excess female mortality by analysing the dynamics of child sex ratios between 1980 and 2015 using country-level life table data. I decompose changes in child sex ratios into a 'fertility' component attributable to prenatal sex selection and a 'mortality' component attributable to sex differentials in postnatal survival. Although reductions in numbers of excess female deaths have accompanied increases in missing female births in all countries experiencing the emergence of prenatal sex selection, relative excess female mortality has persisted in some countries but not others. In South Korea, Armenia, and Azerbaijan, mortality reductions favouring girls accompanied increases in prenatal sex selection. In India, excess female mortality was much higher and largely stable as prenatal sex selection emerged, but slight reductions were seen in the 2000s. In China, although absolute measures showed reductions, relative excess female mortality persisted as prenatal sex selection increased.

Sex selection for non-medical indications: a survey of current pre-implantation genetic screening practices among U.S. ART clinics.

PURPOSE: This study aimed to determine the current percentage of United States (U.S.) assisted reproductive technology (ART) clinics offering sex selection via pre-implantation genetic screening (PGS) for non-medical purposes. METHODS: The authors conducted website review and telephone interview survey of 493 U.S. ART clinics performing in vitro fertilization (IVF) in 2017. Main outcome measures were pre-implantation genetic screening (PGS)/pre-implantation genetic diagnosis (PGD) practices and non-medical sex selection practices including family balancing. RESULTS: Of the 493 ART clinics in the USA, 482 clinics (97.8%) responded to our telephone interview survey. Among all U.S. ART clinics, 91.9% (n = 449) reported offering PGS and/or PGD. Furthermore, 476 clinics responded to survey questions about sex selection practices. Of those ART clinics, 72.7% (n = 346) reported offering sex selection. More specifically among those clinics offering sex selection, 93.6% (n = 324) reported performing sex selection for family balancing, and 81.2% (n = 281) reported performing for elective purposes (patient preference, regardless of rationale for the request). For couples without infertility, 83.5% (n = 289) of clinics offer sex selection for family balancing and 74.6% (n = 258) for non-specific elective reasons. CONCLUSIONS: The majority of U.S. ART clinics offer non-medical sex selection, a percentage that has increased substantially since last reported in 2006.

Risk Factors for Stillbirth: Findings from a Population-Based Case-Control Study, Haryana, India.

BACKGROUND: Stillbirth is a prevalent adverse outcome of pregnancy in India despite efforts to improve care of women during pregnancy. Risk factors for stillbirths include sociodemographic factors, medical complications during pregnancy, intake of harmful drugs, and complications during delivery. The objective of the study was to examine the risk factors for stillbirth with a focus on sex selection drugs (SSDs). METHODS: A population-based case-control study was undertaken in Haryana. Cases of stillbirths were identified from the Maternal Infant Death Review System portal of Haryana state for the months of August-September 2014. A consecutive birth from the same geographical area as the case was selected as the control. The sample size was 325 per group. Mothers were interviewed using a validated tool. Bivariate analyses and logistic regression were conducted to examine the association between risk factors and stillbirth. Attributable risk proportions (ARP) and population attributable risk proportions (PARP) were estimated. RESULTS: The sociodemographic profiles of the cases and controls were similar. History of intake of SSDs [adjusted odds ratio (OR) 2.6, 95% confidence interval (CI) 1.5, 4.5] emerged as a risk factor. Other significant factors were preterm <37 weeks (OR 3.5, 95% CI 2.1, 6.0), history of previous stillbirths (OR 4.0, 95% CI 2.1, 7.8), and complications during labour (OR 3.3, 95% CI 2.1, 5.3). Estimates of the ARP and PARP for intake of SSDs were 0.60 (95% CI 0.32, 0.77) and 0.1 (95% CI -0.13, 0.28), respectively. CONCLUSIONS: SSDs could be attributed as a risk factor in a fifth of the cases of stillbirths. The number needed to harm for the use of SSDs in causing adverse effect of stillbirths was 5, suggesting thereby that for every five mothers exposed to SSDs, one would have stillbirth. Greater efforts are required to inform people about the harmful effects of SSD consumption during pregnancy.

The Dynamics of Son Preference, Technology Diffusion, and Fertility Decline Underlying Distorted Sex Ratios at Birth: A Simulation Approach.

We present a micro-founded simulation model that formalizes the "ready, willing, and able" framework, originally used to explain historical fertility decline, to the practice of prenatal sex selection. The model generates sex ratio at birth (SRB) distortions from the bottom up and attempts to quantify plausible levels, trends, and interactions of son preference, technology diffusion, and fertility decline that underpin SRB trajectories at the macro level. Calibrating our model for South Korea, we show how even as the proportion with a preference for sons was declining, SRB distortions emerged due to rapid diffusion of prenatal sex determination technology combined with small but growing propensities to abort at low birth parities. Simulations reveal that relatively low levels of son preference (about 20 % to 30 % wanting one son) can result in skewed SRB levels if technology diffuses early and steadily, and if fertility falls rapidly to encourage sex-selective abortion at low parities. Model sensitivity analysis highlights how the shape of sex ratio trajectories is particularly sensitive to the timing and speed of prenatal sex-determination technology diffusion. The maximum SRB levels reached in a population are influenced by how the readiness to abort rises as a function of the fertility decline.

Sex ratio at birth in twenty-first century Greece: the role of ethnic and social groups.

The number of male per 100 female live births (defined as the sex ratio at birth, SRB) has been shown to be consistently stable in human populations irrespective of time and geographical location. All over the globe approximately 105 boys are born for every 100 girls and any significant deviation from this 'global average' is considered to be unnatural and is attributed to sex-selective under-reporting of births, sex-selective abortion, sex-selective infanticide or other man-made factors. The present paper uses data on civil registration from 2004-2011 to investigate the sex ratio at birth in modern Greece. It was found that the SRB is extremely masculine when the parents originate from the Indian sub-continent and China. The SRB is also unnaturally high (more than 113 boys per 100 girls) in the case of legitimate births born to Greek mothers who are illiterate. These findings are strong evidence that sex-selective abortions are taking place in Greece within population groups with a certain ethnic and social profile. Other parameters, such as age of mother at birth, birth order, legal status of birth and geographical location, were also investigated and they were found to play a role in the variation of SRB, but not to the extent education and ethnic group do.

Evolution of gender options in multiple pregnancy management.

OBJECTIVE: Fetal reduction (FR) in multiples dramatically improves outcomes. We prioritize FR decisions for health and historically declined to factor gender. As male preferences apparently diminished, our bioethicist encouraged a re-evaluation. METHODS: Three hundred ninety-six patients reducing triplets or twins were categorized as 3➔2, 3➔1, and 2➔1, Major (M) anomaly or minor (m) anomaly, same gender (SG), and those for whom gender preference (GP) was possible. Higher order and non chorionic villus sampling were excluded. FR decisions were prioritized by M anomaly, Suspicious, or m anomaly. If neither, we considered GP. RESULTS: Of 319, 214 (67%) had either M/m or SG. Of those, 3➔2 with gender option: 71/79 chose male and female or had no preferences, one chose male/male, and seven chose female/female. We reduced monochorionic twins in 33/35 3➔1 cases. Of 20 with GP choice, 10 chose male and 10 chose female. Of 162 2➔1, 54 had M or m, 50 were SG, but of the 44 M/F twins, 20 chose male and 24 chose female. CONCLUSIONS: There has been a cultural shift mostly preferring one of each or having no preference. When reducing to one, >50% prefer a girl. In addition to identifying abnormalities, chorionic villus sampling before FR expands patient autonomy.

Artificial insemination field data on the use of sexed and conventional semen in nulliparous Holstein heifers.

This study investigated conception rates and other reproductive outcomes achieved with artificial insemination (AI) of nulliparous Holstein heifers using sexed and conventional semen in a commercial Australian dairy herd in central western New South Wales from January 2004 to April 2009. Retrospective data from on-farm records of 9,870 inseminations of 4,456 heifers were analyzed using several mixed models to assess the effect of temperature and humidity surrounding breeding, insemination sire, artificial insemination technician, service number, and heifer weight and age at breeding on reproductive traits (conception rates, sex ratios, gestation length, and abortion and stillbirth rates). Semen was used from 15 sexed sires and 41 unsexed sires. Sexed semen was primarily used at first and second service. Empirical conception rates of 31.6 and 39.6% were achieved for sexed and unsexed semen respectively, whereas model-based predictions were lower, at 21.3 and 32.1%. Conception rates were significantly affected by insemination sire, sex-sorting, heifer age at breeding, temperature and humidity surrounding breeding, service number, and AI technician. Sexed semen yielded 86% heifers, compared with 48% for conventional semen. Significant predictors of calf sex included semen sexing, gestation length, and insemination sire. Twinning rate was high, at 3.6% for both semen types, and gestation length and heifer weight at breeding were significant predictors of twinning. Abortion rates for sexed and unsexed conceptions were similar at 6.1 and 6.5%, respectively, and were affected by heifer age at breeding. Stillbirth rate was affected by calf sex, twinning, gestation length, and AI technician; semen sorting, age at breeding, and temperature and humidity were marginally significant predictors. No abnormalities were observed in the development of offspring, except for a marginally higher stillbirth rate for sexed calves, a finding that needs further investigation. Many variables influence the breeding outcomes associated with the application of sex-sorted sperm on commercial dairy farms. Recognition and management of these variables will increase the economic return from the investment in sex-sorted sperm.

Desire for sons and subsequent fertility in rural India. A 20-year longitudinal study.

This paper compares the desired fertility of rural Indian women in 1987 with their actual fertility in 2007. Seventy-one respondents who stated definite fertility intentions and had fewer children than desired in 1987 were re-interviewed 20 years later, as part of a larger study. The results indicated that these women had fewer children than intended and stopped childbearing once they reached, or approximated, their desired number of sons. The majority had been sterilized, indicating broad acceptance of lower fertility among rural women and the success of India's family planning efforts, although the practice of sex determination seems also to have played a role. These findings echo those of an earlier longitudinal study of reproductive intentions and outcomes in the same community, demonstrating the persistence of son preference in determining reproductive behaviour, even in the context of low overall fertility. The paper concludes with a discussion of the policy and programme implications of the study's findings.

Distortions of sex ratios at birth in the United States; evidence for prenatal gender selection.

OBJECTIVE: The normal male to female livebirth sex ratio ranges from 1.03 to 1.07. Higher ratios in China, India and Korea reflect prenatal sex selection. We reviewed sex ratios for US births to investigate potential prenatal sex selection. METHODS: We reviewed all US livebirths from 1975 to 2002 using National Center for Health Statistics birth certificates in 4-year intervals. We compared the sex ratios of Blacks, Chinese, Filipinos, Asian Indians and Koreans relative to Whites. We also compared the sex ratios by birth order for first, second and third and more births (third+) from 1991 to 2002. RESULTS: The male to female sex ratio from 1975 to 2002 was 1.053 for Whites, 1.030 (p < 0.01) for Blacks, 1.074 (p < 0.01) for Chinese and 1.073 (p < 0.01) for Filipinos. From 1991 to 2002, the sex ratio increased from 1.071 to 1.086 for Chinese, 1.060 to 1.074 for Filipinos, 1.043 to 1.087 for Asian Indians and 1.069 to 1.088 for Koreans. The highest sex ratios were seen for third+ births to Asian Indians (1.126), Chinese (1.111) and Koreans (1.109). CONCLUSION: The male to female livebirth sex ratio in the United States exceeded expected biological variation for third+ births to Chinese, Asian Indians and Koreans strongly suggesting prenatal sex selection.

Son-biased sex ratios in the 2000 United States Census.

We document male-biased sex ratios among U.S.-born children of Chinese, Korean, and Asian Indian parents in the 2000 U.S. Census. This male bias is particularly evident for third children: If there was no previous son, sons outnumbered daughters by 50%. By contrast, the sex ratios of eldest and younger children with an older brother were both within the range of the biologically normal, as were White offspring sex ratios (irrespective of the elder siblings' sex). We interpret the found deviation in favor of sons to be evidence of sex selection, most likely at the prenatal stage.

Sex of preceding child and birth spacing among Nigerian ethnic groups.

In seeking for more effective ways of fertility control and improvement of maternal and child health through birth spacing in a predominantly patrilineal society like Nigeria, this study explores how the sex of a previous child affects birth interval among ethnic groups, controlling for demographic and socioeconomic variables. The study utilized birth history data from the 2008 Nigeria Demographic and Health Survey. The findings showed that the effect of sex of prior births on the birth interval is slightly significant among the Igbo and the Southern minorities, who tend to desire to have a male child sooner if preceding births were female. Among all the ethnic groups, women who are yet to meet their ideal sex preference have a shorter birth interval than those who have. Apart from the evident sex preferences, these results suggest that Nigerian parents also undertake sex balancing among their children. There is a consistent and strong relationship between the survival of a child and subsequent birth interval, which suggest that women have a short birth interval, and hence a large family size, because they are not certain that their children would survive.

Sex preferences among mothers delivering at Patan Hospital.

BACKGROUND: High sex ratios at birth (SRB) are seen in China, Taiwan, South Korea, parts of India and Vietnam. The imbalance is the result of son preference, accentuated by declining fertility. Prenatal sex determination and female feticides are common in many countries. It is reflected in sex ratio OBJECTIVE: To determine reasons for the preferences for different sex; to find out whether there is altered sex ratio at birth and to find out whether female feticide are common among women who had abortion. METHOD: It is a prospective study. Women who had previous history of abortion and had delivered at Patan Hospital in the year 2066 were interviewed as per questionnaires. RESULTS: Among 560 women with total live births of 965, (462 male and 503 female) during their life time the overall sex ratio was 92 male per 100 female birth; total abortions were 663. Preferences for male were 10%, female 15.4% and either was for 74%. The reason for male preference was to continue family lineage, to bring honor, old age security, and performing funeral rites while the reasons for daughter preferences were that they understand mothers pain, help in household work. The sex ratio of the babies born during the study period was 113 male per 100 female births. The Sex ratio at birth from 1st to 6th deliveries was 61, 79, 101, 210, 286 and 1100 male per 100 female birth respectively. Prenatal sex selection was 8% (by USG) but none had sex selected abortion. CONCLUSION: Sex ratio of those delivered during the study period was skewed (136 boys per 100 girls) towards male. There was shift in SRB in 4th and subsequent pregnancies in favor of boys. As the male sex ratio increased the number of induced abortion decreased in subsequent pregnancies.

Sex ratios at birth in Australia according to mother's country of birth: A national study of all 5 614 847 reported live births 1997-2016.

OBJECTIVES: Son preference and sex selective practices have resulted in a deficit of girls in several countries, primarily across Asia. Emerging evidence indicates that son preference survives migration to Western high-income countries. The objective of this study was to assess male-to-female (M/F) ratios at birth per mother's country of birth in Australia 1997-2016, in total and by parity, and by states/territories and over time. METHODS: Data for this national population-based cross-sectional study were obtained from the National Perinatal Data Collection (NPDC) and included all live births in Australia 1997-2016 (N = 5 614 847). M/F ratios with 95% Confidence Intervals were estimated. RESULTS: The M/F ratio for births to Australian-born mothers was within the expected range (1.03-1.07) regardless of parity and time period. M/F ratios were elevated above the expected range for births to mothers born in China in the total sample (M/F ratio 1.084, 95% confidence interval 1.071-1.097) and at parity 2 (1.175, 1.120-1.231), and for births to mothers born in India at parity 2 (1.146, 1.090-1.204). Parity 2 births were the most consistently male-biased across time. Across states, elevated M/F ratios were identified for both groups in New South Wales (China parity 2: 1.182, 1.108-1.260; India parity 2: 1.182, 1.088-1.285), for births to Chinese-born mothers in Victoria (total births: 1.097, 1.072-1.123; parity 1: 1.115, 1.072-1.159) and Australian Capital Territory (total births: 1.189, 1.085-1.302) and births to Indian-born mothers Western Australia (parity 2: 1.307, 1.122-1.523). CONCLUSIONS: Son preference persists in some immigrant communities after migration to Australia. The consistent pattern of elevated M/F ratios across the larger states indicates that sex imbalances at birth are largely independent of restrictiveness of local abortion laws. Drivers and consequences of son preference in Western high-income settings should be explored to further promote gender equality, and to strengthen support for women who may be vulnerable to reproductive coercion.

Trends in missing females at birth in India from 1981 to 2016: analyses of 2·1 million birth histories in nationally representative surveys.

BACKGROUND: Half of the world's missing female births occur in India, due to sex-selective abortion. It is unknown whether selective abortion of female fetuses has changed in recent years across different birth orders. We sought to document the trends in missing female births, particularly among second and third children, at national and state levels. METHODS: We examined birth histories from five nationally representative household surveys (National Family Health Surveys 1-4 and District Level Household Survey 2) to compute the conditional sex ratio (defined as the number of girls born per 1000 boys depending on previous birth sex) in India during 1981-2016. We estimated decadal variation in conditional sex ratio for 1987-96, 1997-2006, and 2007-16, and quantified trends in the numbers of missing female births for the states constituting >95% of India's population, as well as in 5-year intervals for each survey round. We used multivariate logistic regression to calculate the odds ratio of a second (or third) girl depending on the sex of the earlier child (or children), adjusting for education, wealth, religion, caste, and place of residence. FINDINGS: We assessed 2·1 million birth histories across the five surveys. Applying the conditional sex ratios from the surveys to national births, we found that 13·5 million female births were missing during the three decades of observation (1987-2016), on the basis of a natural sex ratio of 950 girls per 1000 boys. Missing female births increased from 3·5 million in 1987-96 to 5·5 million in 2007-16. Contrasting the conditional sex ratio from the first decade of observation (1987-96) to the last (2007-16) showed worsening for the whole of India and almost all states, among both birth orders. Punjab, Haryana, Gujarat, and Rajasthan had the most skewed sex ratios, comprising nearly a third of the national totals of missing second-born and third-born females at birth. From about 1986, the conditional sex ratio for second-order or third-order births after an earlier daughter or daughters diverged notably from that after an earlier son or sons. From 1981 to 2016, the sex ratio for second-born children after an earlier daughter decreased from 930 (99% CI 869-990) to 885 (859-912), and that for third-born children after two earlier daughters decreased from 968 (866-1069) to 788 (746-830). The probability of missing girls was mostly determined by earlier daughters, even after considering wealth quintile and education levels. The conditional sex ratio among the richest and most educated mothers was most distorted compared with lower wealth and education groups, and generally decreased with time, until a modest improvement in 2007-16. INTERPRETATION: In contrast to the substantial improvements in female child mortality in India, missing female births, driven by selective abortion of female fetuses, continues to increase across the states. Inclusion of a question on sex composition of births in the forthcoming census would provide local information on sex-selective abortion in each village and urban area of the country. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Recent dramatic increase in the male-to-female sex ratio of babies born in Hong Kong.

AIMS: There is a rapid rise in the male-to-female sex ratio at birth in Hong Kong, which coincides with the influx of Mainland Chinese mothers crossing the border to give birth in Hong Kong. Our objective is to explore the sex ratio patterns among Hong Kong Chinese and Mainland Chinese. METHODS: Analysis of the statistics from Hong Kong public hospitals from 2003 to 2007. RESULTS: For the 194,602 babies studied, 140,962 (72.4%) were eligible (Hong Kong Chinese) and 52,741 (27.1%) were non-eligible (Mainland Chinese). The overall sex ratio at birth (defined as males per 1000 females) was 1088; 1078 for eligible and 1116 for non-eligible. For eligible persons, the sex ratios were 1060 for parity 0, 1073 for parity 1 and 1184 for parity 2 or above. For non-eligible persons, the sex ratios were 1047 for parity 0, 1149 for parity 1 and 1745 for parity 2 or above. Non-eligible persons of parity 1 or above were more likely to have sons than eligible persons of same parity (P<0.000). CONCLUSION: We believe that the rapid rise of sex ratio in Hong Kong can be partly explained by the influx of Mainland Chinese who may have practiced sex selection more than Hong Kong Chinese.

Preferences for the sex-composition of children in Europe: a multilevel examination of its effect on progression to a third child.

Comparative research on the preferred sex of children in Western societies has generally focused on women only and ignored the role of gender equity and the need for children's economic support in old age. A multilevel analysis extends existing research by examining, for both men and women and across 24 European countries, the effect of the preferred sex-composition of offspring on whether parents have or intend to have a third child. Using the European Social Survey (2004/5), a multilevel (random coefficient) ordered logit regression of that intention (N = 3,323) and a binary logistic multilevel model of the transition to a third child (N = 6,502) demonstrate the presence of a mixed-sex preference. In countries with a high risk of poverty in old age, a preference for sons is found, particularly for men. In societies where there is lower gender equity, both men and women have a significant preference for boys.