Fat and female fecundity: prospective study of effect of body fat distribution on conception rates.

OBJECTIVES--To study the effect of body fat distribution in women of reproductive age on fecundity. DESIGN--Prospective cohort study of all women who had entered a donor insemination programme. SETTING--One fertility clinic serving a large part of the midwest of the Netherlands. SUBJECTS--Of 542 women attending the clinic for artificial insemination for the first time, 500 women were eligible for study. MAIN OUTCOME MEASURES--Probability of conception per cycle and number of insemination cycles before pregnancy or stopping treatment. RESULTS--A 0.1 unit increase in waist-hip ratio led to a 30% decrease in probability of conception per cycle (hazard ratio 0.706; 95% confidence interval 0.562 to 0.887) after adjustment for age, fatness, reasons for artificial insemination, cycle length and regularity, smoking, and parity. Increasing age was significantly related to lower fecundity (p < 0.05); very lean and obese women were less likely to conceive (p < 0.10) as were women with subfertile partners (p < 0.10). All other exposure variables were not significantly related to fecundity. CONCLUSIONS--Increasing waist-hip ratio is negatively associated with the probability of conception per cycle, before and after adjustment for confounding factors. Body fat distribution in women of reproductive age seems to have more impact on fertility than age or obesity.     

Expectations of assisted conception for infertility.

OBJECTIVE--To provide reliable prognostic information for couples seeking assisted conception. DESIGN--Analysis of four years'' practice (1988-91). SETTING--Private university service linked with NHS reproductive medicine services. PATIENTS--804 couples with various causes of subfertility, median duration five years, median age of women 34 years. INTERVENTIONS--1280 completed cycles: 950 in vitro fertilisation, 144 gamete intrafallopian transfer, and 186 intrauterine insemination and superovulation. MAIN OUTCOME MEASURES--Pregnancy and birth rates per cycle and cumulative pregnancy and take home baby rates per couple. RESULTS--In women under 40 years and men with normal sperm, whatever the cause of infertility, results with in vitro fertilisation improved steadily reaching a pregnancy rate per cycle of 30% (95% confidence interval 26% to 35%) during 1990-1 and birth rate per cycle of 29% (23% to 35%) in 1990. Pregnancy and birth rates for gamete intrafallopian transfer were 36% (28% to 44%) and 26% (17% to 37%) and for intrauterine insemination 18% (12% to 24%) and 16% (10% to 22%). After six cycles cumulative probability of pregnancy was 82% and cumulative take home baby rate 70%. Considering only in vitro fertilisation and gamete intrafallopian transfer after four cycles the pregnancy rate was 78% (66% to 91%). CONCLUSIONS--Conception is less likely in women over 40 and men with sperm dysfunction. For other couples the prognosis for a live birth is at least as good as for fertile couples if they persist with treatment.     

Time to Pregnancy: A Computational Method for Using the Duration of Non-Conception for Predicting Conception

An important problem in reproductive medicine is deciding when people who have failed to become pregnant without medical assistance should begin investigation and treatment. This study describes a computational approach to determining what can be deduced about a couple''s future chances of pregnancy from the number of menstrual cycles over which they have been trying to conceive. The starting point is that a couple''s fertility is inherently uncertain. This uncertainty is modelled as a probability distribution for the chance of conceiving in each menstrual cycle. We have developed a general numerical computational method, which uses Bayes'' theorem to generate a posterior distribution for a couple''s chance of conceiving in each cycle, conditional on the number of previous cycles of attempted conception. When various metrics of a couple''s expected chances of pregnancy were computed as a function of the number of cycles over which they had been trying to conceive, we found good fits to observed data on time to pregnancy for different populations. The commonly-used standard of 12 cycles of non-conception as an indicator of subfertility was found to be reasonably robust, though a larger or smaller number of cycles may be more appropriate depending on the population from which a couple is drawn and the precise subfertility metric which is most relevant, for example the probability of conception in the next cycle or the next 12 cycles. We have also applied our computational method to model the impact of female reproductive ageing. Results indicate that, for women over the age of 35, it may be appropriate to start investigation and treatment more quickly than for younger women. Ignoring reproductive decline during the period of attempted conception added up to two cycles to the computed number of cycles before reaching a metric of subfertility.     

Skin tone,biracial stratification and tri-racial stratification among sperm donors

Abstract

Conception through donor insemination is an attractive option for many couples and single women in the USA, being a relatively simple and inexpensive way of having a baby by a biological birth. Sperm banks provide online catalogues in which sperm donors can be selected according to their physical and social characteristics. One sperm bank's catalogue was analysed based on the pregnancy of selected donors. Three hypotheses were tested related to colourism, biracial stratification and tri-racialism. Specifically, the selection of donors did not reflect: (1) any general preference for a lighter skin tone; (2) a black–white polarity; or (3) any trend towards tri-racialism. Donors who could be identified as Jewish or Muslim were more likely to be selected. Donors whose major was law were less likely to be selected.     

A joint mixed effects dispersion model for menstrual cycle length and time-to-pregnancy

Menstrual cycle patterns are often used as indicators of female fecundity and are associated with hormonally dependent diseases such as breast cancer. A question of considerable interest is in identifying menstrual cycle patterns, and their association with fecundity. A source of data for addressing this question is prospective pregnancy studies that collect detailed information on reproductive aged women. However, methodological challenges exist in ascertaining the association between these two processes as the number of longitudinally measured menstrual cycles is relatively small and informatively censored by time to pregnancy (TTP), as well as the cycle length distribution being highly skewed. We propose a joint modeling approach with a mixed effects dispersion model for the menstrual cycle lengths and a discrete survival model for TTP to address this question. This allows us to assess the effect of important characteristics of menstrual cycle that are associated with fecundity. We are also able to assess the effect of fecundity predictors such as age at menarche, age, and parity on both these processes. An advantage of the proposed approach is the prediction of the TTP, thus allowing us to study the efficacy of menstrual cycle characteristics in predicting fecundity. We analyze two prospective pregnancy studies to illustrate our proposed method by building a model based on the Oxford Conception Study, and predicting for the New York State Angler Cohort Prospective Pregnancy Study. Our analysis has relevant findings for assessing fecundity.     

Age and fertility: can women wait until their early thirties to try for a first birth?

Postponing the start of childbearing raises the question of fertility postponed versus fertility foregone. One of the limitations of previous studies of 'How late can you wait?' is that any observed decline in the probability of conception with age could be due to a decline in fecundability with age or due to a decline in coital frequency with age or due to both factors. Using data from a multinational longitudinal study conducted to determine the daily probability of conception among healthy subjects, a discrete-time event history model with long-term survivors (sterile population) is used to study the relationship between age and fecundability for childless women, while controlling for the pattern of intercourse within a menstrual cycle. The findings suggest that women can wait until their early thirties to try for a first birth, providing that they are not already sterile, as the magnitude of the decline in fecundability is very modest and of little practical importance.     

Optimizing Breeding Decisions for Finnish Dairy Herds

The purpose of this study was to determine the effect of reproductive performance on profitability and optimal breeding decisions for Finnish dairy herds. We used a dynamic programming model to optimize dairy cow insemination and replacement decisions. This optimization model maximizes the expected net revenues from a given cow and her replacements over a decision horizon. Input values and prices reflecting the situation in 1998 in Finland were used in the study. Reproductive performance was reflected in the model by overall pregnancy rate, which was a function of heat detection and conception rate. Seasonality was included in conception rate. The base run had a pregnancy rate of 0.49 (both heat detection and conception rate of 0.7). Different scenarios were modeled by changing levels of conception rate, heat detection, and seasonality in fertility. Reproductive performance had a considerable impact on profitability of a herd; good heat detection and conception rates provided an opportunity for management control. When heat detection rate decreased from 0.7 to 0.5, and everything else was held constant, net revenues decreased approximately 2.6%. If the conception rate also decreased to 0.5 (resulting in a pregnancy rate of 0.25), net revenues were approximately 5% lower than with a pregnancy rate of 0.49. With lower fertility, replacement percentage was higher and the financial losses were mainly from higher replacement costs. Under Finnish conditions, it is not optimal to start breeding cows calving in spring and early summer immediately after the voluntary waiting period. Instead, it is preferable to allow the calving interval to lengthen for these cows so that their next calving is in the fall. However, cows calving in the fall should be bred immediately after the voluntary waiting period. Across all scenarios, optimal solutions predicted most calvings should occur in fall and the most profitable time to bring a replacement heifer into a herd was in the fall. It was economically justifiable to keep breeding high producing cows longer than low producing cows.     

Evaluation of early embryonic mortality in donor insemination by a mathematical model,globally and depending on semen quality

Stating the probability of pregnancy per cycle as P_oP_FP_v, the product of the probabilities of ovulation, fertilization, and egg viability, the model allows an estimate of P_F and P_oP_v for a series of cycles with known insemination timing. Such results obtained from a series of donor insemination (AID) compared with those generally admitted in natural reproduction suggest that the lower pregnancy rate in AID (all the lower when the postthaw motility is low) is owing to a lower egg viability. Since the abortion rate does not seem higher, there might be a sizable rate of very early embryonic deaths in AID perhaps even as early as nondeveloping eggs.     

Investigation and treatment of amenorrhoea resulting in normal fertility.

A simple scheme of investigation and treatment to restore fertility in amenorrhoeic women is described. Fifty-nine patients with amenorrhoea not due to primary ovarian failure were treated variously as appropriate, mainly with clomiphene (25), bromocriptine (15), or human menopausal gonadotrophins (12), and six by diet to increase their weight. All ovulated, and by the end of the study 55 (93%) had conceived, 42 (71%) had delivered at least one surviving child, and five others (8%) were pregnant and awaiting delivery. Conception rates were 49% within two cycles of treatment and 66% within three cycles; using life-table method to standardise the cumulative conception rates by correcting for patients who did not continue as long as others in the study, the expected conception rate was 79% in six cycles, 94% in 12 cycles, and 98% after 16 cycles. The multiple pregnancy rate was 13% and abortion rate 22%. Delivery rate (for a viable baby) were 48% within 11 months of starting treatment and 53% within one year; expected rates were 76% in 18 months and 97% in two years. The results show that a relatively simple scheme of classifying amenorrhoeic disorders endocrinologically followed by treatment directed at inducing ovulation allows amenorrhoeic women without primary ovarian failure to achieve conception and delivery rates equal to those in normal women.     

Effectiveness of abortion as birth control.

Several models used to study the effectiveness of abortion in population limitation are examined. The Keyfitz model, based on the probability that an individual woman will conceive in a given month, is extended and public implications of legal abortions are discussed. A model more appropriate for a population of women rather than a single woman can be developed by relating the probability of conception and the sterile intervals to the number of birth and the number of women in the population. The effectiveness of abortion as a birth control method is studied using this model and includes: 1) abortion effectiveness combined with efficient contraception (95% effective); 2) the sensitivity of abortion to gestation when a contraceptive of lower efficiency is used; 3) these effects modified for prolonged lactation; 4) the effect of changing the monthly probability of conception and the monthly efficiency of contraception. Abortion later in pregnancy is advantageous when efficient contraception is absent. The effectiveness of abortion to gestation is approximately the same whether lactation is included or absent, although abortion is more effective at all gestations and for all contraceptives efficiencies in the absence of lactation. The sensitivity of the effectiveness of abortion to the probability of conception decreases as monthly effectiveness of contraception increases. The probability of conception and the monthly effectiveness of contraception are difficult parameters to measure in the population. The effect of abortion averaged over the entire population at risk of pregnancy is different from its effect on certain subgroups. For U.S. females the probability of conception may be between .06 and .16, and from the model it is indicated that the effectiveness of abortion would be from 1 to 1.13 abortions per live birth. The application of the model suggests that the expenditures for abortion services in this population are a reasonable investment, although investment for efficient contraception is also suggested.     

Lactation, nutrition and fertility and the secretion of prolactin and gonadotrophins in Mopan Mayan women.

The effect of lactation on menstrual cycles, ovulation and conception was studied in a group of non-contracepting Amerindian Mopan Mayan women. Anthropological observations of relevant events were made over a 21-month period. Blood samples were assayed to determine the plasma concentrations of prolactin, luteinising hormone, follicle stimulating hormone, human chorionic gonadotrophin, placental lactogen, oestrogen, progesterone and cortisol. The data show that: frequent and prolonged breast-feeding was associated with a marked increase in plasma prolactin concentrations to levels similar to those in lactating Gaing but higher than those in lactating Scottish women; ovulatory menstrual cycles and pregnancy occurred during frequent lactation; in lactating menstruating women there was an inverse correlation between fat weight and months post-partum. These data suggest that other factors as well as suckling account for the effects of lactation on fecundity.     

The use of the probit model to predict pregnancy status of buffalo based on physio-chemical properties of estrual mucus

Improper timing of artificial insemination with respect to ovulation is one of the major factors hampering the conception rate in buffalo. The present study was an attempt to relate physio-chemical changes in estrual mucus to subsequent pregnancy status in order to find their optimal values for determining the time for artificial insemination (AI). Serum estradiol, total protein and dry matter contents of estrual mucus were evaluated to predict the subsequent pregnancy in 36 buffalo during October 1988 to February 1989. Serum estradiol was determined by radioimmunoassay (RIA); spinnbarkeit, dry matter and total protein were determined by standard methods. Multivariate probit analyses were carried out to relate these variables to subsequent pregnancy status. Elasticity and protein concentration were significantly related to prediction probability of pregnancy status, and they predicted the pregnancy status 86% of the times correctly (P < 0.05). The probability of pregnant animals being correctly classified was 0.76, whereas the corresponding value for non-pregnant animals was 0.95. The present study demonstrated the possibility of using such a statistical model on mucus characteristics for determining proper AI time for better conception rates in Nili-Ravi water buffalo.     

Fertility of high-yielding dairy cows following superovulation and non-surgical recovery of embryos

It was the aim of this investigation to study the combined effect of superovulation and non-surgical recovery on the fertility of the donor animals. Injection of a prostaglandin analogue at the day of collection (days 6–8 after standing heat), significantly shortened the super-ovulatory estrus cycle (21.3 ± 10.0 days), when compared with untreated donor animals (38.7 ± 15.1 days). The prostaglandin treatment, however, also led to more irregular estrous cycles, resulting in a lower pregnancy rate after first insemination (47%) and a need for more inseminations per conception (2.00 ± 1.00), than in animals not treated with prostaglandin analogue (92.3% and 1.06 ± 0.29 AI/conception). For all animals these parameters were 66.6% and 1.60 ± 0.99 AI/conception). The average time from calving to pregnancy was 143.1 ± 34.3 days, slightly longer for prostaglandin treated (148.2 ± 39.4 days) than for untreated animals (137.3 ± 22.8 days). One animal developed endometritis and one had adhesions in the $\text{bursa ovarii}$. It was found that most donors attained normal fertility, and that superovulation was more likely to affect the fertility (abnormal cyclicity, early embryonic mortality e.g.) than the flushing of the uterus. Treatment with a prostaglandin analogue at the day of collection did not improve the subsequent fertility.     

Bayesian inferences on predictors of conception probabilities

Reproductive scientists and couples attempting pregnancy are interested in identifying predictors of the day-specific probabilities of conception in relation to the timing of a single intercourse act. Because most menstrual cycles have multiple days of intercourse, the occurrence of conception represents the aggregation across Bernoulli trials for each intercourse day. Because of this data structure and dependency among the multiple cycles from a woman, implementing analyses has proven challenging. This article proposes a Bayesian approach based on a generalization of the Barrett and Marshall model to incorporate a woman-specific frailty and day-specific covariates. The model results in a simple closed form expression for the marginal probability of conception, and has an auxiliary variables formulation that facilitates efficient posterior computation. Although motivated by fecundability studies, the approach can be used for efficient variable selection and model averaging in general applications with categorical or discrete event time data.     

Effects of preconception lifestyle intervention in infertile women with obesity: The FIT-PLESE randomized controlled trial

BackgroundWomen with obesity and infertility are counseled to lose weight prior to conception and infertility treatment to improve pregnancy rates and birth outcomes, although confirmatory evidence from randomized trials is lacking. We assessed whether a preconception intensive lifestyle intervention with acute weight loss is superior to a weight neutral intervention at achieving a healthy live birth.Methods and findingsIn this open-label, randomized controlled study (FIT-PLESE), 379 women with obesity (BMI ≥ 30 kg/m²) and unexplained infertility were randomly assigned in a 1:1 ratio to 2 preconception lifestyle modification groups lasting 16 weeks, between July 2015 and July 2018 (final follow-up September 2019) followed by infertility therapy. The primary outcome was the healthy live birth (term infant of normal weight without major anomalies) incidence. This was conducted at 9 academic health centers across the United States. The intensive group underwent increased physical activity and weight loss (target 7%) through meal replacements and medication (Orlistat) compared to a standard group with increased physical activity alone without weight loss. This was followed by standardized empiric infertility treatment consisting of 3 cycles of ovarian stimulation/intrauterine insemination. Outcomes of any resulting pregnancy were tracked. Among 191 women randomized to standard lifestyle group, 40 dropped out of the study before conception; among 188 women randomized to intensive lifestyle group, 31 dropped out of the study before conception. All the randomized women were included in the intent-to-treat analysis for primary outcome of a healthy live birth. There were no significant differences in the incidence of healthy live births [standard 29/191(15.2%), intensive 23/188(12.2%), rate ratio 0.81 (0.48 to 1.34), P = 0.40]. Intensive had significant weight loss compared to standard (−6.6 ± 5.4% versus −0.3 ± 3.2%, P < 0.001). There were improvements in metabolic health, including a marked decrease in incidence of the metabolic syndrome (baseline to 16 weeks: standard: 53.6% to 49.4%, intensive 52.8% to 32.2%, P = 0.003). Gastrointestinal side effects were significantly more common in intensive. There was a higher, but nonsignificant, first trimester pregnancy loss in the intensive group (33.3% versus 23.7% in standard, 95% rate ratio 1.40, 95% confidence interval [CI]: 0.79 to 2.50). The main limitations of the study are the limited power of the study to detect rare complications and the design difficulty in finding an adequate time matched control intervention, as the standard exercise intervention may have potentially been helpful or harmful.ConclusionsA preconception intensive lifestyle intervention for weight loss did not improve fertility or birth outcomes compared to an exercise intervention without targeted weight loss. Improvement in metabolic health may not translate into improved female fecundity.Trial registrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02432209","term_id":"NCT02432209"}}NCT02432209.

Richard Legro and colleagues investigate the impact of a preconception weight loss intervention on healthy live birth rates in women with obesity and unexplained infertility.     

Fatal hepatitis E viral infection in pregnant women in Ghana: a case series

ABSTRACT: BACKGROUND: Viral infections during pregnancy can pose serious threats to mother and fetus from the time of conception to the time of delivery. These lead to congenital defects, spontaneous abortion and even death. The definitive diagnosis and management of pregnancy-related viral infections may be challenging especially in less resourced countries. CASE PRESENTATION: We present clinical and laboratory responses to the diagnosis and management of three cases of fulminant hepatitis secondary to Hepatitis E viral infection in pregnancy.Case 1 was a 31-year-old Ghanaian woman who presented with a week's history of passing dark urine as well as yellowish discoloration of the eyes. She subsequently developed fulminant hepatitis secondary to Hepatitis E viral infection, spontaneously aborted at 24 weeks of gestation and later died.Case 2 was also a 31-year-old Ghanaian woman who was admitted with a four-day history of jaundice. She had low grade fever, but no history of abdominal pain, haematuria, pale stool or pruritus. She next developed fulminant hepatitis secondary to Hepatitis E viral infection. However, she did not miscarry but died at 28 weeks of gestation.Case 3 was a 17-year-old Ghanaian woman who was referred to the tertiary health facility on account of jaundice and anaemia. She had delivered a live male infant at maturity of 32 weeks but noticed she was jaundiced and had a presentation of active disease 3 days prior to delivery. The baby was icteric at birth and on evaluation, had elevated bilirubin (mixed type) with normal liver enzymes. Hepatitis E virus infection was confirmed in both mother and baby. However, the jaundice and the hepatomegaly resolved in mother and baby after 5 and 12 days respectively. CONCLUSION: To the best of our knowledge, these are the first documented cases of fatal fulminant hepatic failures resulting from HEV infection in Ghana.     

High fertility does not cause spontaneous intrauterine fetal loss: the determinants of spontaneous fetal loss in Egypt

This study is concerned with a major, though relatively neglected, reproductive health issue: fetal loss. In particular, the determinants of spontaneous intrauterine mortality in Egypt are investigated with stress on the demographic determinants. To this end, a conceptual framework is developed. Using pregnancy history data from a national survey conducted in Egypt in 1995, the determinants of spontaneous intrauterine fetal deaths among currently married women aged 18-45 are examined using multiple logistic models. It is found that the probability of intrauterine fetal loss rises with maternal age. The apparent positive association of the risk with gravidity is shown to be an artifact, due to the heterogeneity among women with respect to the risk of pregnancy loss, the consequent selection process, and reproductive compensation behavior according to the "success/failure" stopping rule. Therefore, high fertility cannot be said to cause spontaneous fetal loss. Two other features of a woman's reproduction are of strong significance, namely, her pregnancy history and spacing among pregnancies. Once a woman suffers from spontaneous fetal loss, the probability of undergoing further pregnancy losses rises sharply. And the shorter the pregnancy interval, the higher the probability of pregnancy loss. Pregnancies conceived after long intervals are less likely to end in loss.     

Therapeutic donor insemination with frozen semen.

Although it is now accepted that cryopreserved semen must, on ethical and medicolegal grounds, be used for donor insemination many clinicians still believe that it has an unacceptably reduced fecundability rate as compared with fresh semen. We studied the outcome of 81 recipients who started therapeutic donor insemination (TDI) treatment during 1986 in a program that used exclusively cryopreserved semen; 55 had never undergone TDI and were receiving the first series (six cycles), 6 were receiving the second series (also six cycles), and 20 had achieved pregnancy through TDI previously and were starting the treatment again. Insemination with semen stored in 0.5-ml French straws was performed daily during the periovulatory period while the modified Insler score was 10 or greater out of 15. A total of 42 (52%) of the recipients became pregnant within six TDI cycles; 4 (10%) had a spontaneous abortion. An average of 4.8 straws were used per cycle among those who became pregnant and 5.1 per cycle among those who did not. On average 2.6 cycles were required to achieve pregnancy. The overall fecundability rate was 14.6%. We conclude that a TDI program involving exclusively frozen semen can be operated with a success rate comparable to rates achieved with fresh semen if a simple, established cryopreservation method and an uncomplicated clinical management protocol are used.     

Incidence,trends, and risks of ectopic pregnancy in a population of women.

In a 20-year longitudinal study on ectopic pregnancy in a defined population of women aged 15-39 years the rate of ectopic pregnancy per 1000 diagnosed conceptions increased from 5.8 during 1960-4 to 11.1 during 1975-9. The mean annual incidence of ectopic pregnancy per 1000 women increased from 0.6 to 1.2 during the same period. The numbers of ectopic pregnancies per 1000 diagnosed conceptions increased with increasing age of the women and were 4.1, in the teenage group 6.9, in women aged 20-29 years, and 12.9 in women aged 30-39. Among 20- to 29-year-old sexually active women at risk of pregnancy who had never had acute salpingitis the rates of ectopic pregnancy per 100 woman-years were the same in those who did not use contraceptives as in those using non-medicated or copper-medicated intrauterine contraceptive devices (IUCDs; 0.3/100 woman years). The risk of an ectopic pregnancy increased sevenfold after acute salpingitis. These findings confirm the increased risk of ectopic pregnancy after salpingitis and suggest that the increase in the incidence of ectopic pregnancy in Lund from 1960 to 1979 was partly accounted for by the use of IUCDs.     

Synchronization of ovulation in beef herds: improved conception rate after and interrupted course of progesterone administration

Administration of 50 mg progesterone in 6 im injections every 48 hours was used to synchronize the estrous cycles of 6 herds of cows and/or heifers. Because of a previous finding that cows in the last 3rd of their estrous cycles when progesterone treatment is begun exhibit lower fertility, such cows were excluded by presynchronization of the herd 8 days prior to the start of treatment by 4 48-hourly injections of 50 mg progesterone. 69%-86% of the animals became pregnant in 4 of the 6 herds during the synchronized estrus, which compares favorably with the average 1st insemination conception figure without synchronization (approximately 70%). Previous conception rates observed averaged approximately 47%.