J. Michael Bedford

Enigmas of mammalian gamete form and function

The gametes of man and some other Eutheria have been manipulated successfully for practical reasons, but many gaps remain in our basic understanding of the way that they function. This situation stems not least from a failure to recognize the extent to which eutherian spermatozoa and eggs, and elements related to their operation, have come to differ from those of other groups. Novel features in the male that reflect this include a radical design of the sperm head with the acrosome seeming to function primarily in egg‐coat binding rather than its lysis, a multifaceted post‐testicular sperm maturation and an androgen/low‐temperature‐regulated system of sperm storage – both tied to the epididymis, a variable male accessory sex gland complex, and descent of the testis and epididymis to a scrotum. In the female, such novelties are represented in a need for sperm capacitation, in an unusual regulation of sperm transport within the oviduct, in the cumulus oophorus and character of the zona pellucida around the small egg, and in a unique configuration of gamete fusion.

The Coevolution of Mammalian Gametes

Mammals, grouped as such because of shared features that include hair, homeothermy, and lactation, are composed of Monotremata (Prototheria), and the Theria, which include Marsupialia (Metatheria), and Eutheria. The latter are often referred to as placental mammals, but this is inappropriate in the strict sense since marsupials also briefly develop a functional placenta.

Ultrastructural evidence of the onset of testicular pathological conditions in the cryptorchid human testis within the first year of life.

Pathological fibrosis of testicular intertubular tissues may be evident in the cryptorchid testis of children 1 year old. A characteristic feature of such testes is massive collagen deposition, which disrupts the regular order of the interstitium, in particular the peritubular layer of cells, by the time the child is 4 years old. These conclusions are based on ultrastructural examination of testicular biopsies collected at orchiopexy from 13 boys with cryptorchidism between 1 and 13 years old. These findings persuade us that orchiopexy should be performed in children about 1 year old and, certainly, no later than 2 years. Otherwise, eventual normal testicular function is highly unlikely.

Evaluation of leuprolide acetate and gonadotropins versus clomiphene citrate and gonadotropins for in vitro fertilization or gamete intrafallopian transfer

A prospective randomized trial was conducted to compare the efficiency of two ovarian stimulation protocols for in vitro fertilization-embryo transfer or gamete intrafallopian transfer. Protocol 1 consisted of clomiphene citrate and human menopausal gonadotropin (hMG) with 55 cycles of 42 patients being evaluated. Protocol 2 had 38 cycles of 34 patients receiving a gonadotropin-releasing hormone agonist (GnRH-a) and hMG. The incidence of a spontaneous luteinizing hormone surge was 38.2% in protocol 1 and 0% in protocol 2. Both protocols had a similar cancellation rate. The total clinical pregnancy rates per oocyte retrieval for patients receiving protocol 1 and protocol 2 were 19.5% and 10.3%, respectively. The difference was not statistically significant. Therefore, as first-line ovulation induction agents, it cannot be concluded that either protocol demonstrates a clear superiority over the other and further trials of the GnRH-a/hMG combination are indicated.

Novelties of conception in insectivorous mammals (Lipotyphla), particularly shrews.

In the order Lipotyphla (Insectivora), certain reproductive features differ quite distinctly from the eutherian norms, and are of interest with regard to the evolution of mammalian gamete function and perhaps for questions of lipotyphlan phylogeny. As seen in one or more members of five lipotyphlan families (shrews, moles, hedgehogs, golden moles, tenrecs), these features can involve the configuration of the male tract including the penis, the morphology of the sperm head, the anatomy of the oviduct and the patterns of sperm transport within it, the character of the cumulus oophorus, and the way in which fertilising spermatozoa interact with the eggs. However, the picture is by no means uniform within the order. Reproductive idiosyncrasies occur variously in the different lipotyphlan families, and appear consistently and strikingly in shrews ‐ the group studied most extensively. Compared to the patterns in most Eutheria, the most interesting anomalies in soricids include (a) the regulation of sperm transport to the site of fertilisation by oviduct crypts, whose arrangement can vary even according to species, (b) a circumscribed matrix‐free cumulus oophorus that appears essential for fertilisation as the inducer of the acrosome reaction, (c) barbs on the acrosome‐reacted sperm head by which it may attach to the zona pellucida.

Plasmanate as a medium supplement for in vitro fertilization

PurposeThe purpose of this study was to evaluate the use of Plasmanate, a protein preparation containing human serum albumin and mixed globulins to autologous preovulatory maternal serum, as an in vitro fertilization (IVF) medium supplement. Plasmanate was used most often in cases involving unexplained infertility, sperm antibodies, and endometriosis or when serum was unavailable.ResultsIn a retrospective analysis of 1019 consecutive IVF cycles, Plasmanate was used as the protein supplement to the fertilization medium in 28.6% and maternal serum was used in 71.4% of the attempts. Attempting to eliminate the effects of different medium lots and laboratory conditions, 450 matched patient cycles were compared using the two protein supplements. Finally, the effects of Plasmanate versus maternal serum were compared in prospective randomized trial on patients diagnosed with tubal infertility who were attempting IVF for the first time. The clinical pregnancy rate was 34% for the Plasmanate group versus 24% for those using maternal serum in the retrospective investigation. However, this trend was reversed in the prospective trial.ConclusionAlthough further investigation is necessary, it appears that Plasmanate is an appropriate protein substitute in patient cases where serum is absent or unsuitable.

Pregnancy achieved through in vitro fertilization with cryopreserved semen from a man with Hodgkin’s lymphoma

Here we present the first report of a successful, term pregnancy after the transfer of oocytes fertilized in vitro with cryopreserved semen from a man with Hodgkins disease. Our review of the literature revealed only three other reports of pregnancies after in vitro fertilization (IVF) using cryopreserved husbands semen

The Bearing of Epididymal Function in Strategies for in Vitro Fertilization and Gamete Intrafallopian Transfer

In vitro fertilization (IVF), first seen as a means of overcoming major female infertility problems, has now emerged also as an often-important adjunct to the resolution of certain types of infertility presented by men. Because of the need for relatively low (ca. l00,OOO) numbers of competent spermatozoa, the techniques of IVF and gamete intra-fallopian transfer (GIFT) enhance the possibility for establishment of a pregnancy by men with a significant degree of oligospermia or asthenospermia. Furthermore, the mode of preparation involved in the “swim-up” of spermatozoa may minimize problems that occur because of the presence of anti-sperm antibodies. In considering the bearing of the epididymis in this area, it is perfectly possible that some cases of male subfertility reflected in a poor quality ejaculate do arise as a result of some fundamental aberration of epididymal function. Unfortunately, there are at present no validated ways of detecting subtle abnormalities of human epididymal function,’ nor the means for their correction if identified. What is known of epididymal function, however, does bear directly on strategies for dealing with the physical problem of bilateral blockage of the duct, either congenital or induced, that results in azoospermia. This condition may sometimes be corrected by epididymovasostomy?.’ In many cases, however, this cannot be performed or the surgery is unsuccessful. Such an outcome leaves one choice-collection of spermatozoa directly from the male reproductive tract. This has been achieved successfully, on occasion, in conjunction with vaginal insemination.‘,’ However, the rather small numbers of spermatozoa that sometimes result from such direct collection or from a spermatocele may often make remote the prospects of pregnancy resulting from vaginal insemination and make recourse to IVF or GIFT the more logical course. This paper, based on current knowledge of events in the epididymis, discusses the relatively simple issue of the factors that may be taken into account in making judgments about sperm collection from the obstructed male duct for such a purpose. There is no doubt that spermatozoa useful for IVF can be collected directly from a discrete segment of the vas deferens or epididymis. This has been achieved following establishment of a spermatocele on the vas deferens‘.’ o r at the corpus/cauda junction of the epididymis8 Furthermore, spermatozoa aspirated directly from the midcorpus region of an obstructed epididymis have established a normal pregnancy through IVFP

Viability of Spermatozoa in the Human Ejaculate After Vasectomy

Ejaculates produced by 82 men between 6 and 19 days after removal of approximately 5 cm of vas deferens were assessed specifically for motility of residual spermatozoa. Several of 23 ejaculates produced 6 to 8 days after vasectomy still contained spermatozoa of the quality and number likely to produce pregnancy. By 13 to 15 days, however, all or the great majority of residual spermatozoa were dead, and in only 1 of 50 men were there numbers of motile spermatozoa possibly compatible with fertility. The results seem to justify more extensive surveys to confirm the absolute or biologic limits of the viability of spermatozoa in the terminal portion of the human male reproductive tract, anticipated here to be 16 to 18 days, as a suggested basis for a standard postvasectomy protocol. Second, these data support the choice of the 3rd postoperative week as the earliest rational moment to confirm the absence of motile spermatozoa, or in their presence to suspect an incomplete block.

Oocyte Structure and the Design and Function of the Sperm Head in Eutherian Mammals

Spermatozoa of eutherian mammals display novel features of form and function whose biological significance is not understood. They express a need for capacitation in the female before they can fertilize, the sperm head has become stabilized to an unusual degree, and is incorporated by the oocyte in a unique manner. These developments may be responses to functional and structural change in the vestments of the oocyte during evolution of the Eutheria.