The prevalence of chromosomal abnormalities in subgroups of infertile men

BACKGROUND

The prevalence of chromosomal abnormalities is assumed to be higher in infertile men and inversely correlated with sperm concentration. Although guidelines advise karyotyping infertile men, karyotyping is costly, therefore it would be of benefit to identify men with the highest risk of chromosomal abnormalities, possibly by using parameters other than sperm concentration. The aim of this study was to evaluate several clinical parameters in azoospermic and non-azoospermic men, in order to assess the prevalence of chromosomal abnormalities in different subgroups of infertile men.

METHODS

In a retrospective cohort of 1223 azoospermic men and men eligible for ICSI treatment, we studied sperm parameters, hormone levels and medical history for an association with chromosomal abnormalities.

RESULTS

The prevalence of chromosomal abnormalities in the cohort was 3.1%. No association was found between chromosomal abnormalities and sperm volume, concentration, progressive motility or total motile sperm count. Azoospermia was significantly associated with the presence of a chromosomal abnormality [15.2%, odds ratio (OR) 7.70, P < 0.001]. High gonadotrophin levels were also associated with an increased prevalence of chromosomal abnormalities (OR 2.96, P = 0.013). Azoospermic men with a positive andrologic history had a lower prevalence of chromosomal abnormalities than azoospermic men with an uneventful history (OR 0.28, P = 0.047). In non-azoospermic men, we found that none of the studied variables were associated with the prevalence of chromosomal abnormalities.

CONCLUSIONS

We show that the highest prevalence of chromosomal abnormalities is found in hypergonadotrophic azoospermic men with an uneventful andrologic history.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Hormone-dependent placental manipulation of breast cancer cell migration

BACKGROUND

Breast cancer during pregnancy is often more advanced than in non-pregnant women. Nevertheless, no case of metastasis inside the placenta has been reported. Previously, we showed that placental-explants eliminated breast cancer cells from their surroundings, due to cell-death and elevated migration. Our objective was to find the underlying mechanisms of these phenomena.

METHODS AND RESULTS

Our model contained Michigan Cancer Foundation 7 (MCF7) or T47D cells co-cultured with and without human placental explants. Microarray analysis, validated by quantitative PCR, of MCF7 following their placental co-culture suggested activation of estrogen (E2) signaling. As extensive cross-talk exists between E2 and progesterone, their involvement in mediating placental effects on breast cancer cells was tested. Indeed, addition of E2 and progesterone receptor (ER and PR) inhibitors to the co-culture system reduced cancer cell motility, yet did not alter cell-cycle or death. E2 and progesterone concentrations in placental media were found to be similar to those of early pregnancy blood levels. Interestingly, placental-breast cancer co-culture media contained lower progesterone (P < 0.05) and higher E2 (200%, P < 0.05) levels than placentae cultured separately. Placental supernatant and E2 and progesterone at placental levels were sufficient to increase MCF7 and T47D migration and invasion (P < 0.05), yet did not alter MCF7 cell-cycle or death. Furthermore, placental supernatant elevated p38 and Jun N-terminal kinase (JNK) phosphorylation in both cell lines (P < 0.05). Inhibitors of JNK, ER and PR reversed MCF7 and T47D motility induced by the placenta, suggesting their involvement.

CONCLUSIONS

We suggest that E2 and progesterone contribute to cell migration away from placental areas. We hypothesize that they may increase metastatic spread to other organs in pregnancy.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

First-trimester bleeding characteristics associate with increased risk of preterm birth: data from a prospective pregnancy cohort

BACKGROUND

Prior evidence linking first-trimester bleeding with preterm birth (PTB, <37 weeks gestation) risk has been inconsistent and may be biased by subject selection and/or incomplete documentation of bleeding episodes for all participants. Prior studies have not carefully examined the role of bleeding characteristics in PTB risk. In the present study, we estimate the association between first-trimester bleeding and PTB in a non-clinical prospective cohort and test whether bleeding characteristics better predict risk.

METHODS

Women were enrolled in Right from the Start (2000–2009), a prospective pregnancy cohort. Data about bleeding and bleeding characteristics were examined with logistic regression to assess association with PTB.

RESULTS

Among 3978 pregnancies 344 were PTB and 3634 term. Bleeding was reported by 986 (26%) participants. After screening candidate confounders, only multiple gestations remained in the model. Bleeding associated with PTB [odds ratio (OR)adjusted = 1.40, 95% confidence interval (CI) 1.09–1.80]. Risk did not vary by race/ethnicity. Compared with non-bleeders, PTB risk was higher for bleeding with red color (ORadjusted = 1.92, 95% CI, 1.32–2.82), for heavy episodes (ORadjusted = 2.40, 95% CI 1.18–4.88) and long duration (ORadjusted = 1.67, 95% CI 1.17–2.38).

CONCLUSIONS

Bleeding associated with PTB was not confounded by common risk factors for bleeding or PTB. PTB risk was greatest for women with heavy bleeding episodes with long duration and red color and would suggest that combining women with different bleeding characteristics may affect the accuracy of risk assessment. These data suggest a candidate etiologic pathway for PTB and warrant further investigation of the biologic mechanisms.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Lipopolysaccharide induces cytokine production and decreases extravillous trophoblast invasion through a mitogen-activated protein kinase-mediated pathway: possible mechanisms of first trimester placental dysfunction

BACKGROUND

Defects in extravillous trophoblast (EVT) function could contribute to placental dysfunction resulting in adverse obstetrical outcomes. Adverse obstetrical outcomes have been highly correlated with intrauterine infection; however, the mechanisms linking infection to placental dysfunction remain unclear. We investigated the effects of inflammation on EVT cytokine production and invasion early in pregnancy and determined the cell signaling pathways mediating this response.

METHODS AND RESULTS

In our model of inflammation, EVT cells, isolated following first trimester pregnancy terminations (n= 6) were stimulated with lipopolysaccharide (LPS). LPS induced a dose-dependent increase in interleukin (IL)-8 and IL-6 protein production (P < 0.01) and decreased EVT invasion (P = 0.01) versus control. The LPS-mediated changes in cytokine production (P < 0.001) and invasion (P < 0.001) were reversed by dexamethasone (DEX). Exposure to LPS resulted in an increase in mitogen-activated protein kinase (MAPK) signaling pathway phosphorylation, including p44/42 MAPK (P < 0.01), p38 MAPK (P < 0.05), MAPK extracellular signal-regulated kinase 1/2 (MEK1/2) (P< 0.01) and stress-activated protein kinase/c-Jun N-terminal kinase (JNK; P < 0.001), which was reversed by DEX (P < 0.05) for all MAPKs except p38. MAPK-specific inhibitors to MEK1/2 (U0126), p38 MAPK (SB 202190) and JNK (SP 600125) significantly reversed the LPS-mediated increase in IL-6 (P < 0.001) and IL-8 (P < 0.001) production. While U0126 reversed the LPS-induced decrease in EVT invasion (P < 0.001), SB 202190 (P < 0.001) and SP 600125 (P< 0.001) decreased EVT invasion, further indicating that MEK1/2 phosphorylation may be inflammation dependent while p38 MAPK and JNK phosphorylation occurs independently of an inflammatory stimulus.

CONCLUSIONS

LPS increased IL-8 and IL-6 and decreased EVT invasion through activation of MAPK signaling. MEK1/2 activation may contribute to placental dysfunction, in the setting of inflammation-associated adverse obstetrical outcomes.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Non-invasive metabolomic profiling of Day 2 and 5 embryo culture medium: a prospective randomized trial

BACKGROUND

Near infrared (NIR) spectroscopy is a technology proposed to facilitate non-invasive screening for the most optimal human embryo for uterine transfer. It has been proposed that the NIR spectral profile of an embryo's spent culture medium can be used to generate a viability score that correlates to implantation potential. As the initial proof of principle studies were all retrospective, our aim was to investigate whether NIR spectroscopy on spent embryo culture medium in an on-site, prospective setting could improve the ongoing single embryo transfer (SET) pregnancy rate after Day 2 and 5 transfers.

METHODS

We conducted a single-centre, double-blinded, randomized controlled trial in which the NIR group was compared with a control group. The primary outcome was the clinical pregnancy rate after 6–7 weeks of gestation per randomized patient. In the control group embryo selection was based only on traditional morphological evaluation while in the treatment group NIR spectroscopy was added to the morphological evaluation.

RESULTS

The study was terminated early as the analysis of the Data Safety Monitoring Board showed a very low conditional power of superiority for the primary outcome. Of the 752 patients calculated to be included in the study, 164 and 163 patients were randomized into the NIR and control groups, respectively. No significant difference in the ongoing pregnancy rate per randomized patient was found between the NIR and the control group, 34.8 versus 35.6%, (P= 0.97). The proportional difference between the study groups mean was –0.8% (95% confidence interval –11.4 to 10.2).

CONCLUSIONS

This study shows that adding NIR spectroscopy, in its present form, to embryo morphology does not improve the chance of a viable pregnancy when performing SET. The NIR technology appears to need further development before it can be used as an objective marker of embryo viability.

CLINICAL TRIALS IDENTIFIER

ISRCTN23817363.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Human embryonic development after blastomere removal: a time-lapse analysis

BACKGROUND

Blastomere biopsy of human embryos is performed for preimplantation genetic diagnosis (PGD). The impact on further development is largely unexplored, though studies on mice suggest an influence on the hatching process. The objective of this study was to evaluate the effect of blastomere biopsy on early human embryonic development using time-lapse analysis.

METHODS

Embryos from couples undergoing PGD treatment or IVF/ICSI were included. In the PGD group, 56 human embryos had one blastomere biopsied. As controls, 53 non-biopsied IVF/ICSI embryos were selected. All embryos were cultured until 5 days after fertilization in a time-lapse incubator (EmbryoScope™). Images of embryos were acquired every 20min. Time-points of key embryonic events were registered, and development in the two groups was compared.

RESULTS

Duration of the biopsied cell-stage in the PGD group was longer than in the control group (P < 0.001), causing biopsied embryos to reach subsequent embryonic stages until hatching at significantly later time-points (Pcompaction < 0.001; Pmorula < 0.001; Pearlyblast < 0.001; Pfullblast = 0.01), but with unchanged intervals. Embryos in the PGD group started hatching at the same time-point as the control group, but had a smaller diameter (P < 0.001), and a thicker zona pellucida (P < 0.001) when hatching. Time-lapse videos revealed that in the control group, expansion of the blastocyst caused continuous thinning of zona pellucida until the blastocyst hatched, whereas in the PGD group the blastocyst hatched through the opening in zona pellucida artificially introduced prior to the biopsy.

CONCLUSIONS

We find that blastomere biopsy prolongs the biopsied cell-stage, possibly caused by a delayed compaction and alters the mechanism of hatching.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Cytoskeletal analysis of human blastocysts by confocal laser scanning microscopy following vitrification

BACKGROUND

Vitrification of human blastocysts is being used increasingly to cryopreserve supernumerary embryos following IVF. In this study, we investigate the effects of aseptic vitrification on the cytoskeleton and development of human blastocysts, by analysing survival rates and spindle and chromosome configurations by fluorescence and confocal laser scanning microscopy.

METHODS

A total of 55 fresh blastocysts and 55 day 5 dimethylsulphoxide/ethylene glycol vitrified blastocysts, which were allowed to remain in culture for 24 h post-warming, were rapidly fixed in ice cold methanol, and immunostained with an a-tubulin antibody to visualize microtubules in combination with antibodies against acetylated tubulin (to visualize spindles, poles and mid bodies), gamma tubulin (to identify spindle poles) and 4(6-diamidino-2-phenylindole) to visualize DNA.

RESULTS

In total, 213 spindles were analysed in the control (fresh) group of which 183/213 (85.9%) were normal, 20/213 (9.4%) were abnormally shaped, 9/213 (4.2%) were multipolar and 1/213 (0.5%) was monopolar. A total of 175 spindles were analysed in the vitrified group, of which 120/175 (68.6%) were normal, 39/175 (22.3%) were abnormally shaped, 10/175 (5.7%) were multipolar and 6/175 (3.4%) were monopolar. The incidence of multipolar spindles was similar in the two groups, but the level of abnormally shaped spindles, often associated with chromosome lagging, or congression failure, was significantly higher in the vitrified group compared with the fresh group (P< 0.05).

CONCLUSIONS

The high survival rate following thawing and the large proportion of normal spindle/chromosome configurations suggests that vitrification at the blastocyst stage on Day 5 does not adversely affect the development of human embryos and the ability of spindles to form and continue normal cell divisions. However, there was a significantly higher incidence of abnormal spindles in the vitrified group compared with the fresh group, notably of spindles with a focused and an unfocused pole as well as chromosome bridging and disorganized middle spindle fibres at telophase. Further investigation is warranted to elucidate the mitotic stages that are more vulnerable to damage during vitrification, the fate of the abnormal spindles and any potential effects that may be reflected on the chromosomal constitution of the developing blastocysts.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

First experiences with hysterosalpingo-foam sonography (HyFoSy) for office tubal patency testing

BACKGROUND

This study was conducted to describe the first experiences with hysterosalpingo-foam sonography (HyFoSy) as a first step routine office procedure for tubal patency testing.

METHODS

A prospective observational cohort study was started in a university affiliated teaching hospital. In 2010, 73 patients with subfertility and a low risk of tubal pathology were examined. A non-toxic foam containing hydroxymethylcellulose and glycerol was applicated through a cervical applicator for contrast sonography (HyFoSy). Tubal patency was determined by transvaginal ultrasonographic demonstration of echogenic dispersion of foam in the Fallopian tube and/or the peritoneal cavity. Only in case patency could not be demonstrated, a hysterosalpingography (HSG) was performed as a control.

RESULTS

In 67 out of 73 (92%) patients, a successful procedure was performed. In 57 out of 73 (78%) cases, there was no further need for a HSG. In five patients (5/73; 7%) tubal occlusion was confirmed by HSG and in five patients (5/73; 7%) there was discordance between HyFoSy and HSG. Of 73 patients, 14 (19%) conceived within a median of 3 months after the procedure.

CONCLUSIONS

HyFoSy is a successful procedure to demonstrate tubal patency as a first step office procedure.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Donor age is a major determinant of success of oocyte donation/recipient programme

BACKGROUND

In recent years, particularly in developed countries, women have tended to delay childbirth until over 40 years of age. Our study aims to identify whether the donor's age or recipient's age influences the pregnancy and live birth rate following oocyte recipient cycles.

METHODS

A population study included 3889 fresh oocyte recipient cycles. Pregnancy and live delivery rates were compared in recipient age groups (<35, 35–39, 40–44 and ≥45 years) and donor age groups (<30, 30–34, 35–39 and ≥40 years).

RESULTS

The highest live birth rate was of cycles in donors aged 30–34 years (25.0%), it decreased (P< 0.05) to 24.1% in donors aged <30 years, 20.7% in donors aged 35–39 years and 11.5% in donors aged ≥40 years. The multivariate analysis showed no significant differences in the success by recipient's age. Compared with cycles in donors aged 30–34 years, cycles in donors aged 35–39 years had 14 and 18% less chance to achieve a pregnancy [adjusted rate ratio (ARR) 0.86, 95% confidence interval (CI) 0.75–0.98] and a live delivery (ARR 0.82, 95% CI 0.71–0.96), while cycles in donors aged 40 years or older had 42 and 54% less chance to achieve a pregnancy (ARR 0.58, 95% CI 0.41–0.84) and a live delivery (ARR 0.46, 95% CI 0.29–0.73).

CONCLUSIONS

Older recipients with younger donors did not have a poorer pregnancy outcome compared with younger recipients with younger donors. Choosing a donor aged <35 years would increase the chance of pregnancy and live delivery for older recipients.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Surrogate in vitro fertilization outcome in typical and atypical forms of Mayer-Rokitansky-Kuster-Hauser syndrome

BACKGROUND

The genital malformations in Mayer–Rokitansky–Küster–Hauser syndrome (MRKH) are frequently accompanied by associated malformations whose forms were recently classified as typical (isolated uterovaginal aplasia/hypoplasia) and atypical (the addition of malformations in the ovary or renal system). The aim of this study was to compare the surrogate IVF performance of women with typical and atypical forms including their chances of achieving pregnancy.

METHODS

The follow-up data on a total of 102 cycles of surrogate IVF in 27 MRKH patients treated in our department between 2000 and 2010 were analysed. Twenty patients with the typical form who underwent 72 IVF cycles were compared with seven patients with the atypical form who underwent 30 IVF cycles. The various examined parameters of these intended mothers were age, hormonal profile during controlled ovarian hyperstimulation and laboratory outcome.

RESULTS

The mean number of gonadotrophin ampoules needed for stimulation and treatment duration was significantly higher in the atypical form (3600 ± 1297IU for 13 ± 2.3 days versus 2975 ± 967 IU for 11.6 ± 1.6 days, P≤ 0.01). Serum estradiol and progesterone levels measured on the hCG administration day were similar. A significantly higher mean number of follicles 12.6 ± 6 versus 8.9 ± 5.4, P≤ 0.03, metaphase II (MII) oocytes 8.7 ± 5.1 versus 6.7 ± 4.8, P≤ 0.05, fertilizations 6 ± 3.6 versus 4.4 ± 3.3, P≤ 0.03 and cleaving embryos 5.7 ± 3.8 versus 4.1 ± 3.3, P≤ 0.01 were available in patients with the typical form compared with those with the atypical form, respectively. There was no significant difference in fertilization rate, cleavage rate or the mean number of transferred embryos. Embryo quality of the transferred ones and pregnancy rate per cycle were also similar between the two groups.

CONCLUSIONS

Women with the typical form of MRKH needed fewer gonadotrophins and for a shorter duration for ovarian hyperstimulation. The mean number of follicles, oocytes, MII oocytes, fertilizations and cleaving embryos was higher among women with the typical form. Pregnancy rates were similar since the available number and quality of transferred embryos to the surrogate mother were not affected.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Development of clinical priority access criteria for assisted reproduction and its evaluation on 1386 infertile couples in New Zealand

BACKGROUND

In New Zealand ranking patients for elective, publicly funded procedures uses clinical priority access criteria (CPAC). A CPAC to prioritize patients seeking assisted reproductive technology (ART) was developed in 1997 and implemented nationwide in 2000. This study describes the development of the ART CPAC tool and its evaluation on 1386 couples referred to a single tertiary service from 1998 to 2005.

METHODS

A total of 48 health professionals and consumers assisted in criteria development. A score between 0 and 100 points was calculated for each couple and those who reached ≥65 points were eligible for publicly funded ART. Couples beneath the treatment threshold were placed on active review; the review being the date the score was calculated to reach the treatment threshold. Couples who would never be eligible or who were on active review were offered private treatment. Treatments and outcomes (spontaneous and treatment dependent live birth pregnancies) were used to evaluate the criteria.

RESULTS

Three social criteria (duration infertility, number of children and sterilization status) and two objective criteria (diagnosis and female age) formed the priority score. Of the evaluated couples, 643 (46%) were eligible within 1 year of referral (Group 1), 451 (33%) >1–5 years from referral (Group 2) and 292 (21%) couples were never eligible (Group 3). The predominant ART was IVF. A total of 480 couples had at least one IVF treatment with 404 (84%) having publicly funded treatment. A total of 762 (55%) women gave birth, 473 from treatment and 289 spontaneously. Group 1 had more pregnancies from treatment while Group 2 had most pregnancies overall being mainly from spontaneous pregnancies. Compared with Group 3 cases the hazard ratio using time to spontaneous live birth pregnancy for Group 1 couples was significantly lower, 0.51 (95% confidence interval 0.36–0.74) and for Group 2 cases significantly higher, 1.86, (1.35–2.58). Treatments using ART were evaluated for the three eligibility groups, with the never eligible divided into women age <40 (Group 3a) and woman age ≥40 at referral (Group 3b). Compared with Group 1 cases the hazard ratio to treatment dependent live birth pregnancy was similar for Groups 2 and 3a but significantly lower for Group 3b (0.37, 0.14–0.90).

CONCLUSIONS

The clinical priority access score was able to discriminate between the chance of pregnancy with and without treatment and those offered and not offered treatment. The CPAC is a useful model for informing the allocation of public funding for ART in other countries.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

The fiscal outcome of artificial conception in Brazil–creating citizens in developing countries

BACKGROUND

Infertility is an important health issue, but only a small fraction of the affected population receives treatment in Brazil, because it is not covered by the government or private health insurance plans. We developed a generational accounting-based mathematical model to assess the direct economic result of creating a citizen through IVF in different economic scenarios, and the potential economic benefit generated by the individual and his/her future offspring.

METHODS

A mathematical model analyzes the revenues and expenses of an IVF-conceived individual over his lifetime. We calculated the net present value (NPV) of an IVF-conceived citizen, and this value corresponds to the fiscal contribution to the government by an individual, from birth through his predicted life expectancy. The calculation used discount rates of 4.0 and 7.0% to depreciate the money value by time.

RESULTS

A 4.0% discount rate represents the most favorable economic scenario in Brazil, and it results in an NPV of US$ 61 428. A 7.0% discount rate represents a less favorable economic reality, and it results in a debit of U$ 563, but this debt may be compensated by his/her future offspring.

CONCLUSIONS

The fiscal contribution generated by each IVF-conceived citizen can justify an initial government investment in infertility treatment. Poor economic times in Brazil can sometimes result in a fiscal debt from each new IVF-conceived child, but this initial expenditure may be compensated by the fiscal contribution in the next generation.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

Effect of infertility treatment and pregnancy-related hormones on breast cell proliferation in vitro

BACKGROUND

Breast cancer development involves a series of mutations in a heterogeneous group of proto-oncogenes/tumor suppressor genes that alter mammary cells to create a microenvironment permissive to tumorigenesis. Exposure to hormones during infertility treatment may have a mutagenic effect on normal mammary epithelial cells, high-risk breast lesions and early-stage breast cancers. Our goal was to understand the association between infertility treatment and normal and cancerous breast cell proliferation.

METHODS

MCF-10A normal mammary cells and the breast cancer cell lines MCF-7 [estrogen receptor (ER)-positive, well differentiated] and HCC 1937 (ER-negative, aggressive, BRCA1 mutation) were treated with the weak ER activator clomiphene citrate and hormones that are increased during infertility treatment. Direct effects of treatment on cell proliferation and colony growth were determined.

RESULTS

While clomiphene citrate had no effect on MCF-10A cells or MCF-7 breast cancer cells, it decreased proliferation of HCC 1937 versus untreated cells (P= 0.003). Estrogen had no effect on either MCF-10A or HCC 1937 cells but, as expected, increased cell proliferation (20–100 nM; P≤0.002) and colony growth (10–30 nM; P< 0.0001) of MCF-7 cells versus control. Conversely, progesterone decreased both proliferation (P= 0.001) and colony growth (P= 0.01) of MCF-10A cells, inhibited colony size of MCF-7 cells (P= 0.01) and decreased proliferation of HCC 1937 cells (P= 0.008) versus control. hCG (100 mIU/ml) decreased both proliferation (P ≤ 0.01) and colony growth (P ≤ 0.002) of all three cell lines.

CONCLUSIONS

Although these data are preclinical, they support possible indirect estrogenic effects of infertility regimens on ER-positive breast cancer cells and validate the potential protective effect of pregnancy-related exposure to hCG.

Source:
http://humrep.oxfordjournals.org/rss/current.xml

The poor responder in IVF: is the prognosis always poor? A systematic review

BACKGROUND

In IVF treatment a considerable proportion of women are faced with a low number of oocytes retrieved. These poor responders have reduced pregnancy rates compared with normal responders. However, this may not be applicable to all poor responders. This review aims at identifying patient characteristics and ovarian reserve tests (ORT) that will determine prognosis for pregnancy in poor responders.

METHODS

A systematic search was conducted in PubMed, Embase, Cochrane and SCOPUS databases in April 2010. Studies regarding patient characteristics or ORT in poor responders and their pregnancy prospects were included. All included papers were summarized in descriptive tables.

RESULTS

Nineteen studies were included. Pooled data of six studies comparing poor and normal responders demonstrated clearly lower pregnancy rates in poor responders (14.8 versus 34.5%). Ten studies indicated that older poor responders have a lower range of pregnancy rates compared with younger (1.5–12.7 versus 13.0–35%, respectively). Four studies showed that pregnancy prospects become reduced when fewer oocytes are retrieved (0–7% with 1 oocyte versus 11.5–18.6% with 4 oocytes). Five studies concerning pregnancy rates in subsequent cycles suggested a more favourable outcome in unexpected poor responders, and if ≥2 oocytes were retrieved.

CONCLUSIONS

Poor responders are not a homogeneous group of women with regards to pregnancy prospects. Female age and number of oocytes retrieved in particular will modulate the chances for pregnancy in current and subsequent cycles. Applying these criteria will allow the identification of couples with a reasonable prognosis and balanced decision-making on the management of poor responders.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

Demographic and medical consequences of the postponement of parenthood

BACKGROUND

Across the developed world couples are postponing parenthood. This review assesses the consequences of delayed family formation from a demographic and medical perspective. One main focus is on the quantitative importance of pregnancy postponement.

METHODS

Medical and social science databases were searched for publications on relevant subjects such as delayed parenthood, female and male age, fertility, infertility, time to pregnancy (TTP), fetal death, outcome of medically assisted reproduction (MAR) and mental well-being.

RESULTS

Postponement of parenthood is linked to a higher rate of involuntary childlessness and smaller families than desired due to increased infertility and fetal death with higher female and male age. For women, the increased risk of prolonged TTP, infertility, spontaneous abortions, ectopic pregnancies and trisomy 21 starts at around 30 years of age with a more pronounced effects >35 years, whereas the increasing risk of preterm births and stillbirths starts at around 35 years with a more pronounced effect >40 years. Advanced male age has an important but less pronounced effect on infertility and adverse outcomes. MAR treatment cannot overcome the age-related decline in fecundity.

CONCLUSIONS

In general, women have partners who are several years older than themselves and it is important to focus more on the combined effect of higher female and male age on infertility and reproductive outcome. Increasing public awareness of the impact of advanced female and male age on the reproductive outcome is essential for people to make well-informed decisions on when to start family formation.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

Long-term endocrine side effects of childhood Hodgkin’s lymphoma treatment: a review

BACKGROUND

Since childhood cancer survival has increased, long-term effects of treatment have gained interest. Childhood Hodgkin's lymphoma has been treated successfully for decades now. We provide an overview of the literature on long-term endocrine side effects, such as gonadal dysfunction and growth retardation, as a result of childhood Hodgkin's lymphoma treatment.

METHODS

A comprehensive search of the Pubmed database was performed.

RESULTS

We identified 16 studies (10 studies: 298 male survivors and 6 studies: 230 female survivors) about gonadal dysfunction. In survivors treated with alkylating agents or pelvic radiotherapy, severe gonadal damage is described. Recovery was rarely described. Seven studies (481 survivors) about bone mineral density (BMD) and growth were identified. The effects on BMD appear to be small. Data on growth are scarce, but show that radiotherapy in a dose of >30 Gy including the spine, especially in pre-pubertal children, results in reduced height. We included 10 studies (4012 survivors) about thyroid complications. Hypothyroidism is the most common thyroid disorder after radiotherapy. There is also a significant incidence in thyroid carcinoma after low-dose radiation. In survivors treated with chemotherapy only, hypothyroidism and thyroid cancer have not been reported.

CONCLUSIONS

The severity of endocrine toxicity after childhood Hodgkin's lymphoma depends on the type of treatment. Gonadal dysfunction seems to be the most severe endocrine long-term effect, especially after treatment with alkylating agents or pelvic radiotherapy. The knowledge obtained in specific follow-up programmes for paediatric cancer survivors will help to find the optimal balance between curability and long-term side effects.

Source:
http://humupd.oxfordjournals.org/rss/current.xml

Ovarian antral folliculogenesis during the human menstrual cycle: a review

BACKGROUND

Ovarian follicles undergo dynamic morphologic and endocrinologic changes during the human menstrual cycle. The physiologic mechanisms underlying recruitment and selection of antral follicles in women are not fully elucidated.

METHODS

A comprehensive review of >200 studies was conducted using PubMed. The objective was to compare and contrast different perspectives on human antral folliculogenesis.

RESULTS

Antral folliculogenesis has been studied using histologic, endocrinologic and/or ultrasonographic techniques. Different theories of antral follicle recruitment include: (i) continuous recruitment throughout the menstrual cycle; (ii) recruitment of a ‘cohort’ of antral follicles once in the late-luteal phase or early-follicular phase of each cycle and (iii) recruitment of two or three ‘cohorts’ or ‘waves’  during each cycle. Generally, a single dominant follicle is selected in the mid-follicular phase of each cycle and this follicle ovulates at mid-cycle. However, a dominant follicle may also be selected during anovulatory waves that precede the ovulatory wave in some women.

CONCLUSIONS

There is increasing evidence to indicate that multiple waves of antral follicles develop during the human menstrual cycle. Ovarian follicular waves in women are comparable with those documented in several animal species; however, species-specific differences exist. Enhancing our understanding of the endocrine and paracrine mechanisms underlying antral follicular wave dynamics has clinical implications for understanding age-related changes in reproductive function, optimizing hormonal contraceptive and ovarian stimulation regimens and identifying non-invasive markers of the physiologic status of follicles which are predictive of oocyte competence and assisted reproduction outcomes.

Source:
http://humupd.oxfordjournals.org/rss/current.xml