Annika K. Ludwig

Physical health at 5.5 years of age of term-born singletons after intracytoplasmic sperm injection: results of a prospective, controlled, single-blinded study.

OBJECTIVE To study the health of children born after ICSI and of spontaneously conceived control children at the age of 4-6 years. DESIGN Prospective, controlled, blinded study. SETTING Tertiary-care center. PATIENT(S) Two hundred seventy-six term-born singletons conceived by ICSI and 273 matched spontaneously conceived singletons at the age of 5.5 years. INTERVENTION(S) Detailed physical examination, interview of the parents, and collection of data from each childs examination booklet. MAIN OUTCOME MEASURE(S) Biometrical data; current health status; acute, chronic and childhood illnesses; hospitalizations; and surgeries. RESULT(S) Detailed physical examination did not reveal any relevant differences between ICSI and spontaneously conceived children. There were no relevant differences regarding the incidence of childhood illnesses, acute or chronic illnesses, accidents, and surgeries up to the age of 5.5 years. However, a history of undescended testicles was found significantly more often in boys born after ICSI (5.4% vs. 0.7%), with the consequence that they had significantly more urogenital surgery (19.2% vs. 8.9%). Significantly more ICSI children had been hospitalized (37.6% vs. 27.2%), although we did not find any specific reason for the increased hospitalization rate. CONCLUSION(S) Other than an increased risk of undescended testicles and therefore an increase in urogenital surgeries in ICSI boys, the physical health of ICSI children was comparable to that of spontaneously conceived children at the age of 5.5 years.

Distribution of persistent organochlorine contaminants in infertile patients from Tanzania and Germany

AbstractPurpose: To test whether environmental pollutants could affect fertility in humans. Methods: 31 women and 16 men from Tanzania and 21 couples from Germany were included (n=89). Pesticides and polychlorinated biphenyls were measured in serum, follicular fluid or seminal plasma by gaschromatography and related to sperm quality and pregnancy rates. Results: Higher concentrations of DDT+DDE and dieldrin in Tanzania and higher concentrations of PCBs in Germany and in men were detected. All compounds showed higher concentrations in serum and lowest concentrations in seminal plasma. A lower pregnancy rate in German women with high serum concentrations of DDT+DDE was observed. The toxins had no impact on sperm quality. Conclusions: The distribution of toxins between agricultural and industrial countries is different. Seminal plasma seems to be inert against chemicals. In patients with high serum concentrations of DDT and DDE pregnancy rates were impaired.

Neuromotor development and mental health at 5.5 years of age of singletons born at term after intracytoplasmatic sperm injection ICSI: results of a prospective controlled single-blinded study in Germany

OBJECTIVE To assess the neurodevelopmental health of children born after intracytoplasmatic sperm injection (ICSI). DESIGN Prospective controlled blinded study. SETTING Tertiary care center. PATIENT(S) A total of 276 term-born singletons conceived by ICSI and 273 matched spontaneously conceived (SC) singletons at the age of 5.5 years. MAIN OUTCOME MEASURE(S) Neuromotor development assessed by a detailed neurologic examination, including the standardized motor test MOT 4-6, and emotional/behavioral development and intelligence assessed with the Kaufman-Assessment Battery for Children. RESULT(S) There were no significant differences between ICSI children and control children regarding the neurologic examination, motor skills, emotional/behavioral development, and intelligence. CONCLUSION(S) The ICSI children born at term develop normally, similar to SC children.

Spontaneous pregnancy after successful ICSI treatment: evaluation of risk factors in 899 families in Germany.

There are only scarce data on the incidence of spontaneous pregnancy in infertility patients. Contraception after infertility treatment is another topic that has been neglected so far. Therefore, a questionnaire was sent to 1614 couples with a child conceived by intracytoplasmic sperm injection (ICSI) aged 4-6 years. A total of 899 couples responded (response rate 55.7%). A total of 10.9% of couples had used contraception. Of the couples that had actively tried to conceive, 20.0% had conceived spontaneously, resulting in a live-birth rate of 16.4%. 74.5% of these pregnancies were conceived within 2 years after delivery. A further 26.6% of couples conceived again by ICSI, with a live-birth rate of 20.9%. Maternal age was the only prognostic factor for spontaneous conception. Parents of multiples after ICSI did not have a higher chance of spontaneous conception than parents of singletons. Couples can be counselled that one out of five couples conceive spontaneously after successful ICSI. Even when assuming that none of the families that were lost to follow-up had conceived spontaneously, one out of eight couples would have conceived spontaneously. Therefore, it is important to counsel patients about the possibility of natural conception and necessity to use contraception despite their history of subfertility.

Assessment of vision and hearing in children conceived spontaneously and by ICSI: a prospective controlled, single-blinded follow-up study

Long-term follow-up studies on the health of children born after assisted reproduction technologies are mandatory. Vision and hearing are the most important senses that continue to develop during childhood. There are few reports on vision and hearing in preschool children born after assisted conception. This prospective controlled blinded follow-up study examined 276 term-born singleton intracytoplasmic injection (ICSI) children and 273 spontaneously conceived controls at a mean age of 5.5 years and performed detailed vision and hearing test and clinically examined eyes and ears. There was no significant difference between ICSI and control children regarding the occurrence of vision or hearing impairments. Unsurprisingly, children with abnormalities in otoscopy were more likely to have an abnormal hearing test compared with children without abnormalities. Only 8.5% of ICSI parents and 25.4% of control parents whose children showed an abnormal hearing test knew about the hearing problems of their child. In conclusion, there was no difference in the development of hearing and vision in ICSI children and spontaneously conceived controls. But only few parents knew about hearing problems of their child after undergoing routine screening examinations. Parental interviews would therefore not be sufficient in order to assess vision and hearing in follow-up studies.

Can we sense ART? The blinded examiner is not blind-a problem with follow-up studies on children born after assisted reproduction.

In a prospective, controlled, blinded follow-up study of children born after intracytoplasmic sperm injection (ICSI), blinded examiners correctly intuited the mode of conception (ICSI versus spontaneous) in three out of four children, which must be considered when interpreting outcome data for children born after assisted reproduction.

Perturbations in finger length and digit ratio (2D:4D) in ICSI children

Intracytoplasmic sperm injection (ICSI) is used to overcome severe male-factor infertility where males are azoospermic or have poor quality spermatozoa. Perturbations of finger length (short finger length adjusted for height and high second-to-fourth digit ratio, or 2D:4D) have been described in azoospermic men and men who are rated as having low sexual attractiveness. High 2D:4D has been described in women with high fecundity. Such perturbations may be related to endocrine regulation of some homeobox genes. This study compared finger length and 2D:4D in singleton children conceived with the help of ICSI with those in naturally conceived singleton controls. Participants were recruited from centres in Germany and the UK. There were 211 children conceived by ICSI and 195 controls. Finger length was measured from photocopies of the ventral surface of the hand. In comparison to controls, male and female ICSI children had shorter fingers after correction for height. There was also evidence that female ICSI children may have higher 2D:4D than female controls. Perturbations in finger length in ICSI children may be inherited from their fathers and, in the case of boys, could be associated with lower fertility and reduced sexual attractiveness. For ICSI females, increased 2D:4D may be associated with increased fertility.

Oral contraception enhances growth hormone responsiveness to hyper- and hypoglycaemia.

Diabet. Med. 29, 345–350 (2012)

Impact of glycemic variations on the regulation of androgen metabolism in obese women with polycystic ovary syndrome

OBJECTIVE To assess the influence of alterations in glucose concentrations on androgen levels in patients with polycystic ovary syndrome (PCOS) and in healthy controls. DESIGN Prospective, controlled study. SETTING Tertiary care center. PATIENT(S) Seven patients with PCOS and 20 healthy controls. INTERVENTION(S) Hyperinsulinemic glucose clamp study with stepwise reduction of the plasma glucose level from hyperglycemia to hypoglycemia. MAIN OUTCOME MEASURE(S) Concentrations of insulin, C-peptide, cortisol, T, androstenedione, 17-hydroxyprogesterone, DHEA, and DHEAS during hyperglycemia, euglycemia, and hypoglycemia. RESULT(S) Total T levels and the free androgen index were significantly higher in the PCOS group at baseline and throughout the clamp. The levels of T, androstenedione, DHEAS, and 17-hydroxyprogesterone were not influenced by short-term changes of plasma glucose concentrations in both groups. However, hypoglycemia led to a significant increase in DHEA levels in PCOS patients as well as in controls. Cortisol levels were not increased during hypoglycemia in either group. CONCLUSION(S) In contrast to men, androgen levels are not influenced by short-term changes of plasma glucose levels in PCOS patients and in healthy women. However, DHEA concentrations increase with decreasing glucose levels independently from an activation of the hypothalamic-pituitary-adrenal axis. This supports a gender difference regarding the counterregulatory hormone response to hypoglycemia.

Wie geht es den Kindern nach reproduktionsmedizinischer Behandlung

ZusammenfassungDrei bis 5 % aller Kinder werden nach einer Form der assistierten Reproduktion geboren. Die Schwangerschaften verlaufen komplizierter und mit mehr perinatalen Komplikationen als solche, die spontan bei fertilen Paaren eintreten. Ursache dafür scheint auch ein nicht näher fassbares, mit der Subfertilität assoziiertes Hintergrundrisiko zu sein. Allerdings spielen möglicherweise weitere Faktoren wie die ovarielle Stimulation und die damit einhergehende unphysiologische Entwicklung des Endometriums eine relevante Rolle. Wenn Kinder am Termin gesund geboren werden, sprechen die Daten dafür, dass diese Kinder sich postnatal weitestgehend unauffällig entwickeln. Nach wie vor wird ein diskret erhöhtes onkologisches Risiko diskutiert, das sich zwar von dem spontan konzipierter signifikant unterscheidet, sich aber kaum in absoluten Zahlen niederschlägt. Erste Daten zur Pubertätsentwicklung und Surrogatparameter für nach einer ICSI (intrazytoplasmatische Spermieninjektion) konzipierten Jungen lassen vermuten, dass ggf. mit einer geringeren Fertilität im späteren Leben zu rechnen ist. Weitere Daten dazu sind notwendig.AbstractBetween 3 and 5% of children born in Germany are conceived by treatments of assisted reproduction (ART). These pregnancies have a more complicated course with more perinatal complications compared to spontaneously conceived pregnancies of fertile couples. Subfertility seems to be a risk factor for these complications, since subfertile couples who conceive spontaneously face similar risks to those with pregnancies after ART. However, other risk factors seem to be involved, including ovarian stimulation, which leads to a nonphysiologically developed endometrium. A child who is born at term and healthy is most likely to develop normally. There is still ongoing discussion whether there is a slightly increased oncological risk for these children, although the absolute risk remains low. Surrogate markers of later fertility in boys born after ICSI (intracytoplasmic sperm injection) give rise for concern. However, more data are necessary.