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IDEAL MEANS OF FERTILITY CONTROL ?
717
function.’ Since an unprejudiced assessment must also consider possible beneficial effects of iron deficiency, we have recently examined one such effect, and referred to another in a recent paper in this journal.’ Statements relating to the importance of iron deficiency in our community have for long been based on estimates of the proportion of subjects found to have levels of circulating haemoglobin below an arbitrary " lower limit of normal " (usually 12.0 g. per 100 ml.). Evaluations in such terms have been current for so long that they seem to have acquired a right not to be questioned. We would suggest, however, that such an approach is misleading and assessment must be based on epidemiological studies using realistic indices of morbidity. It is perhaps of interest that veterinary surgeons, who base their evaluation of iron deficiency on growth-rates, susceptibility to infection, and performance, do not usually diagnose anxmia in farm animals until hxmoglobin levels have fallen from a mean of about 13 g. per 100 ml. to about 7 g. or less.5 While your readers may be more concerned with the health of human beings than veal calves, it is of interest that the prevalence of hxmoglobin levels below 8 g. per 100 ml. in women in our community is well below 1%, even in the elderly.6 M.R.C. Epidemiological Research
MEIOSIS IN XYY MEN
motor
Unit (South Wales), Cardiff.
P. C. ELWOOD.
IDEAL MEANS OF FERTILITY CONTROL ?
SIR,-The suggestion of Dr. Speidel and Dr. Ravenholt (March 14, p. 565) that " the prostaglandins " may be the means of fertility control in the future is interesting, but the practical application presents many problems. While agreeing that some prostaglandins are effective in the initiation of uterine contractions and the production of an abortion, we do not agree that they fulfil the first requirement of the ideal a means of fertility control as defined in the letter-i.e., "
non-toxic ... substance ". Nausea, vomiting, and diarrhoea often occur with the dose of r.G. necessary to produce an abortion; vasodilatation, migraine, and chest pain have been reported when higher doses of E1 have been infused.7 We have found that up to 4 mg. of P.G.E’1 or E2 administered as a titrated infusion may be needed to produce an abortion. Sandberg et al.estimated that 10-20°0 ofp.G.E. introduced into the posterior fornix is absorbed. For an effective dose of 4 mg. to be absorbed, 20-40 mg. of P.G.E. would have to be placed in the vagina. It is difficult to think of a solvent that would maintain this amount of P.G. in solution in the acid pH of the vagina, in a volume small enough to impregnate a tampon. Women vary in their response to prostaglandin. Even with intravenous administration, the P.G. effect can continue for half an hour after cessation of the infusion. An undesirable side-effect occurring after intra-vaginal administration
SIR,-Thompson et al.l and Melnyk et al. have reported the occurrence of only normal primary spermatocytes in seven
XYY males. I should like
to
report abnormal findthree XYY males, a few primary
ings in testicular-biopsy specimens from and a presumptive YY bivalent in spermatocytes in
one of these. born in 1933, body-height 207 cm., is one of 2 XYY males found among 15 men belonging to a club for unusually tall people (the King Size Club). He is married and has a healthy daughter with a 46,XX chromosome constitution. Blood-groups and serum types were compatible with legitimate paternity. Subject 2, born in 1941, body-height 206 cm., is attending a security hospital. Subject 3, born in 1948, body-height 202 cm., was referred for cytogenetic investigation with a preliminary diagnosis of gigantism/acromegaly. He had a 46,XX twin sister. Neither subject 2 nor subject 3 has any children. All have a 47,XYY chromosome constitution without evidence of mosaicism as judged from an analysis of 100 or more cells from lymphocyte cultures. The two Y chromosomes were identified by their characteristic morphology and by autoradiography. In subjects 2 and 3 the Y chromosomes were the size of the G chromosomes, while they were slightly larger than these chromosomes in subject 1. Semen analysis in subject 1 showed oligoasthenospermia in four samples (11-18 million per ml., progressive motility medium percentage of motile cells 30-45% and morphologically normal cells 50-60%) and a normal sperm-count in one (60 million per ml.). No semen specimen could be obtained from subject 2. Two specimens from subject 3 revealed azoospermia (7-9 spermatozoa in the sediment after centrifugation). Histological examination of a testicular-biopsy specimen from subject 1 showed normal-sized tubules with all stages of spermatocytogenesis, but with an increased number of degenerating cells in some tubules. Subject 2 had some tubules of normal size and all stages of spermatocytogenesis, and other somewhat smaller tubules with an arrest before or at the primary-spermatocyte level as well as increased degeneration. This latter type of tubule was also found in subject 3. In this case about half of the tubules contained mainly Sertoli cells, although a few meiotic cells showed arrest before or at the primary-spermatocyte level.
Subject 1,
1. 2.
Thompson, H., Melnyk, J., Hecht, F. Lancet, 1967, ii, 831. Melnyk, J., Thompson, H., Rucci, A. J., Vanasek, F., Hayes,
S.
ibid. 1969, ii, 797.
could be expected to continue even longer despite removal of the tampon, owing to slow absorption of any P.G. remaining in the vagina. Similar problems could occur with depot
injections. Institute of Obstetrics and
Gynæcology, Queen Charlotte’s Maternity Hospital, London W.6.
ARNOLD GILLESPIE JOHN M. BEAZLEY.
3. 4.
Elwood, P. C., Hughes, D. Unpublished. Elwood, P. C., Mahler, R., Moore, F., Welsby, E. Lancet, March 21, 1970, p. 589. 5. Underwood, E. J. The Mineral Nutrition of Livestock. Rome, 1966. 6. Elwood, P. C. Geront. clin., Basel (in the press). 7. Carlson, L. A., Ekelund, L. A., Oro, L. Acta med. scand. 1968, 183, 423. 8. Sandberg, F., Ingelman-Sundberg, A., Joelsson, I., Ryden, G. in Prostaglandin (edited by S. Bergstrom and B. Samuelsson); p. 91. New York, 1967.
Fig. 1-Primary spermatocyte from subject 2: 24 bodies including univalentX (curved arrow) and G-sized bivalents (straight arrows).
function.’ Since an unprejudiced assessment must also consider possible beneficial effects of iron deficiency, we have recently examined one such effect, and referred to another in a recent paper in this journal.’ Statements relating to the importance of iron deficiency in our community have for long been based on estimates of the proportion of subjects found to have levels of circulating haemoglobin below an arbitrary " lower limit of normal " (usually 12.0 g. per 100 ml.). Evaluations in such terms have been current for so long that they seem to have acquired a right not to be questioned. We would suggest, however, that such an approach is misleading and assessment must be based on epidemiological studies using realistic indices of morbidity. It is perhaps of interest that veterinary surgeons, who base their evaluation of iron deficiency on growth-rates, susceptibility to infection, and performance, do not usually diagnose anxmia in farm animals until hxmoglobin levels have fallen from a mean of about 13 g. per 100 ml. to about 7 g. or less.5 While your readers may be more concerned with the health of human beings than veal calves, it is of interest that the prevalence of hxmoglobin levels below 8 g. per 100 ml. in women in our community is well below 1%, even in the elderly.6 M.R.C. Epidemiological Research
MEIOSIS IN XYY MEN
motor
Unit (South Wales), Cardiff.
P. C. ELWOOD.
IDEAL MEANS OF FERTILITY CONTROL ?
SIR,-The suggestion of Dr. Speidel and Dr. Ravenholt (March 14, p. 565) that " the prostaglandins " may be the means of fertility control in the future is interesting, but the practical application presents many problems. While agreeing that some prostaglandins are effective in the initiation of uterine contractions and the production of an abortion, we do not agree that they fulfil the first requirement of the ideal a means of fertility control as defined in the letter-i.e., "
non-toxic ... substance ". Nausea, vomiting, and diarrhoea often occur with the dose of r.G. necessary to produce an abortion; vasodilatation, migraine, and chest pain have been reported when higher doses of E1 have been infused.7 We have found that up to 4 mg. of P.G.E’1 or E2 administered as a titrated infusion may be needed to produce an abortion. Sandberg et al.estimated that 10-20°0 ofp.G.E. introduced into the posterior fornix is absorbed. For an effective dose of 4 mg. to be absorbed, 20-40 mg. of P.G.E. would have to be placed in the vagina. It is difficult to think of a solvent that would maintain this amount of P.G. in solution in the acid pH of the vagina, in a volume small enough to impregnate a tampon. Women vary in their response to prostaglandin. Even with intravenous administration, the P.G. effect can continue for half an hour after cessation of the infusion. An undesirable side-effect occurring after intra-vaginal administration
SIR,-Thompson et al.l and Melnyk et al. have reported the occurrence of only normal primary spermatocytes in seven
XYY males. I should like
to
report abnormal findthree XYY males, a few primary
ings in testicular-biopsy specimens from and a presumptive YY bivalent in spermatocytes in
one of these. born in 1933, body-height 207 cm., is one of 2 XYY males found among 15 men belonging to a club for unusually tall people (the King Size Club). He is married and has a healthy daughter with a 46,XX chromosome constitution. Blood-groups and serum types were compatible with legitimate paternity. Subject 2, born in 1941, body-height 206 cm., is attending a security hospital. Subject 3, born in 1948, body-height 202 cm., was referred for cytogenetic investigation with a preliminary diagnosis of gigantism/acromegaly. He had a 46,XX twin sister. Neither subject 2 nor subject 3 has any children. All have a 47,XYY chromosome constitution without evidence of mosaicism as judged from an analysis of 100 or more cells from lymphocyte cultures. The two Y chromosomes were identified by their characteristic morphology and by autoradiography. In subjects 2 and 3 the Y chromosomes were the size of the G chromosomes, while they were slightly larger than these chromosomes in subject 1. Semen analysis in subject 1 showed oligoasthenospermia in four samples (11-18 million per ml., progressive motility medium percentage of motile cells 30-45% and morphologically normal cells 50-60%) and a normal sperm-count in one (60 million per ml.). No semen specimen could be obtained from subject 2. Two specimens from subject 3 revealed azoospermia (7-9 spermatozoa in the sediment after centrifugation). Histological examination of a testicular-biopsy specimen from subject 1 showed normal-sized tubules with all stages of spermatocytogenesis, but with an increased number of degenerating cells in some tubules. Subject 2 had some tubules of normal size and all stages of spermatocytogenesis, and other somewhat smaller tubules with an arrest before or at the primary-spermatocyte level as well as increased degeneration. This latter type of tubule was also found in subject 3. In this case about half of the tubules contained mainly Sertoli cells, although a few meiotic cells showed arrest before or at the primary-spermatocyte level.
Subject 1,
1. 2.
Thompson, H., Melnyk, J., Hecht, F. Lancet, 1967, ii, 831. Melnyk, J., Thompson, H., Rucci, A. J., Vanasek, F., Hayes,
S.
ibid. 1969, ii, 797.
could be expected to continue even longer despite removal of the tampon, owing to slow absorption of any P.G. remaining in the vagina. Similar problems could occur with depot
injections. Institute of Obstetrics and
Gynæcology, Queen Charlotte’s Maternity Hospital, London W.6.
ARNOLD GILLESPIE JOHN M. BEAZLEY.
3. 4.
Elwood, P. C., Hughes, D. Unpublished. Elwood, P. C., Mahler, R., Moore, F., Welsby, E. Lancet, March 21, 1970, p. 589. 5. Underwood, E. J. The Mineral Nutrition of Livestock. Rome, 1966. 6. Elwood, P. C. Geront. clin., Basel (in the press). 7. Carlson, L. A., Ekelund, L. A., Oro, L. Acta med. scand. 1968, 183, 423. 8. Sandberg, F., Ingelman-Sundberg, A., Joelsson, I., Ryden, G. in Prostaglandin (edited by S. Bergstrom and B. Samuelsson); p. 91. New York, 1967.
Fig. 1-Primary spermatocyte from subject 2: 24 bodies including univalentX (curved arrow) and G-sized bivalents (straight arrows).