A True Hermaphrodite Chimera Resulting from Embryo Amalgamation after in Vitro Fertilization

Abstract

IGH rates of successful pregnancy after in vitro fertilization depend on placing more than one embryo into the mother, a practice resulting in a 30-to-35-fold increase in dizygotic-twin deliveries. 1 Increased frequencies of twinassociated anomalies might also therefore be expected. Chimerism, the presence in a single person of cells derived from two or more zygotes, is one such rare anomaly. It is usually ascertained through anomalous blood-grouping results or (for XX/XY chimeras) sex reversal or intersex.We used DNA polymorphisms to investigate a 46,XX/46,XY hermaphrodite conceived by in vitro fertilization. We found not only that the child is a chimera, but also that he must have resulted from amalgamation of two embryos, each derived from an independent, separately fertilized ovum. CASE REPORTThe mother was a 31-year-old woman with primary infertility. Hormonal and laparoscopic investigation indicated a normal pelvis and normal ovulation. Her partner, who was 41 years old, had had a child by another partner but was severely oligozoospermic. The woman was given buserelin and human menopausal gonadotropins, after which 18 oocytes were harvested, of which 15 were fertilized in vitro with anonymous donor sperm and maintained in separate dishes. Two days after insemination (the fourcell stage), three embryos were transferred to the woman. Ultrasonography 36 days after transfer showed a single fetus and sac. A 3.46-kg infant was delivered vaginally at term; he had a normal right testis and an undescended left testis, with otherwise normal male genitalia. At the age of six months, the left testis was palpable at the inguinal ring. Surgical exploration at the age of 15 months revealed a hernial sac containing an abnormal gonad and vas deferens. These structures were excised; they proved on histologic examination to be an ovary with a fallopian tube attached H to a horn of uterus. Karyotyping of peripheral-blood lymphocytes then revealed two cell lines, one 46,XX and the other 46,XY.At the age of 20 months, the infant's serum follicle-stimulating hormone and luteinizing hormone concentrations were normal for his age, both basally and in response to gonadotropin-releasing hormone. The basal serum testosterone concentration was normal ( Ͻ 20 ng per deciliter [ Ͻ 0.7 nmol per liter]) and rose normally to 180 ng per deciliter (6.3 nmol per liter) three days after a single intramuscular injection of 2000 IU of human chorionic gonadotropin. Ultrasonography at three years eight months revealed an apparently normal right testis in the scrotum and normal kidneys, bladder, and pelvic structures. At laparoscopy at four years four months, the right vas deferens and testicular vessels appeared to be normal; no female genital structures were seen. A skin biopsy was performed. Subsequently, the child has grown and developed normally, with height at the 90th percentile and weight at the 75th percentile. He has no neurodevelopmental abnormalities, and he attends a regular school. METHODSInformed consent for all genetic investigations ...

Developmental outcome of very low birth weight twins conceived by assisted reproduction techniques

“…However, recent evidence has suggested that infants conceived by ART are not biologically identical to naturally conceived infants. ICSI and IVF have been reported to increase chimerism in DC twins 13 as well as imprinting disorder.…”

Do monochorionic dizygotic twins increase after pregnancy by assisted reproductive technology?

“…ART, e.g., IVF, assisted hatching by breaching of the zona pellucida, and/or ET at the blastocyst stage, has been noted to increase the rate of multiple pregnancy (twins, triplets, and even quintuplets) and MZT twinning by embryo splitting (Behr et al 2000;da Costa et al 2001;Tarlatzis et al 2002;Milki et al 2003;Blickstein et al 2003;Ghulmiyyah et al 2003;Edi-Osagie et al 2003). Also, ART is sometimes associated with congenital anomalies, IUGR and TTTS in a fetus, and/or fetal death (Giltay et al 1998;Strain et al 1998;Sills et al 2000;Daniel et al 2000;Cohen 2003;Unger et al 2004) . MC DZT may be another problem associated with ART.…”

True Hermaphroditism in a Phenotypic Male without Ambiguous Genitalia: An Unusual Presentation at Puberty

“…Different hypotheses have been proposed to explain whether it is generated by chimerism (two cellular lines from different zygotes) or by mosaicism (different cell lines derived from the same zygote) [11,12,13]. At present, the analysis of DNA polymorphisms allows to distinguish both maternal and paternal contributions to the genotype [11, 12, 14].…”