Jeanne M. Yovich

The fertilization of human oocytes by spermatozoa from men with antispermatozoal antibodies in semen

Seventy-two couples, including 15 with antispermatozoal antibodies in the male partners semen, were studied in a program of in vitro fertilization and embryo transfer. Cases were further subclassified as normospermic or oligospermic and antispermatozoal antibodies were assessed with categorization into the respective human immunoglobulin classes as determined using the indirect immunobead test. The study reveals that fertilization is significantly reduced (P<0.001) only if both IgA and IgG antibodies are present in semen but there is no reduction if either class is present alone. The fertilization rate of oocytes is significantly reduced (P<0.001) by sperm from oligospermic samples, and there is a further reduction in those cases with combined IgA/IgG antispermatozoal antibodies.

Use of the acrosome reaction to ionophore challenge test in managing patients in an assisted reproduction program: a prospective, double-blind, randomized controlled study

OBJECTIVE To assess the utility of the acrosome reaction (AR) to ionophore challenge test in determining the sperm treatment protocols for patients undergoing assisted reproduction. DESIGN, SETTING, PATIENTS One hundred twenty-one couples undergoing an IVF-ET or GIFT procedure from January to July 1992 were included in this prospective study. All cases had a preliminary semen analysis within the previous 3 months and an AR to ionophore challenge test was carried out unless an acceptable fertilization rate occurred on previous IVF. For those patients whose AR to ionophore challenge score was below the accepted fertile range of > or = 10%, a second AR to ionophore challenge test was performed after exposure of sperm to the stimulant pentoxifylline. Couples then were managed by assisted reproduction with randomized allocation of oocytes for fertilization with a standard sperm preparation or with added sperm stimulants, either 3.6 mM pentoxifylline alone or combined with 3.0 mM 2-deoxyadenosine. The study was double-blind with neither the patients nor the embryologist knowing the AR to ionophore challenge result at the time of the IVF procedure. MAIN OUTCOME MEASURES Data from the preliminary semen analyses and AR to ionophore challenge scores were correlated with the fertilization rates achieved using control and treated sperm preparations. The rates of total fertilization failure and the numbers of clinical pregnancies occurring in each subgroup were also recorded. RESULTS All AR to ionophore challenge groups showed normal sperm counts except the groups with poor AR to ionophore challenge, which demonstrated reduced sperm counts. The group with normal AR to ionophore challenge scores or previous normal fertilization showed satisfactory fertilization rates with either control or treated sperm, although some individual cases showed reduced fertilization with treated sperm. The fertilization rate for the group with low AR to ionophore challenge scores improved significantly with pentoxifylline, and the benefit was greatest when this had been predicted from the AR to ionophore challenge studies. Cases with persisting poor AR to ionophore challenge despite pentoxifylline showed no significant improvement in fertilization rates with sperm exposed to either sperm stimulant regimens. Poor AR to ionophore challenge scores were also predictive of total fertilization failure, but this problem was reduced by sperm stimulation. The AR to ionophore challenge score at 10% cutoff level showed optimal levels of sensitivity (82.1%), highest negative predictive value (82.1%), and lowest false negative rate (17.9%). CONCLUSIONS The AR to ionophore challenge test is useful in the assessment and management of the male factor in assisted reproduction. It can be used to identify the majority of cases who will benefit from the use of sperm stimulants.

A pregnancy achieved using sperm from the epididymal caput in idiopathic obstructive azoospermia

This case report describes the first pregnancy to be achieved by assisted conception using sperm aspirated from the head of the epididymis in an azoospermic man with idiopathic obstructive azoospermia

Hormonal profiles in the follicular phase, luteal phase and first trimester of pregnancies arising from in‐vitro fertilization

Summary. The hormonal profiles for oestradiol‐17β, progesterone, prolactin and β‐human chorionic gonadotrophin (β‐hCG) are documented for the first 24 pregnancies arising from in‐vitro fertilization during a collaborative project between the University of Western Australia and PIVET Laboratory. All patients had ovarian follicle stimulation with clomiphene citrate, sometimes combined with human menopausal gonadotrophin and all had oocyte recovery undertaken 36 h after injection o f 5000 i.u. hCG. The follicular phase profile indicated that patients were admitted for the hCG injection when oestradiol‐17β levels were around 1500 pmol/l per follicle with a dimension of 1·6 cm on ultrasound. Luteal phase data indicated that oestradiol‐17β and progesterone levels were two to three times higher than that expected during spontaneous conception cycles and those pregnancies which subsequently aborted had significantly lower levels in the late luteal phase. During pregnancy elevated oestradiol‐17β and progesterone levels were maintained through the early weeks during organogenesis while the β‐hCG profile was similar to that reported for spontaneous pregnancies arising without ovarian stimulation. Six women aborted and the other 18 pregnancies have generated 22 infants.

The Management of Oligospermic Infertility by in Vitro Fertilization

The fertilization rates of mature preovulatory oocytes aspirated from 156 women treated by in vitro fertilization were analyzed as a function of spermatozoal density and motility and the findings were correlated with the category of infertility (chronic oligospermia, tubal disease, endometriosis, serum antibodies to spermatozoa in the female, and unexplained infertility). Overall reduced fertilization rates were found in all cases if the semen sample presented on the day of fertilization demonstrated less than or equal to 5 million motile spermatozoa per milliliter, less than 40% motile forms, or the combined findings of less than 20 million per ml and less than or equal to 60% motile forms. Where the husband was known to have chronic oligospermia, reduced fertilization was found if the semen on the day of fertilization contained less than 20 million spermatozoa per ml and less than 12 million motile spermatozoa per milliliter. For cases of unexplained infertility, a poor fertilization rate was noted if the semen demonstrated less than 60% progressively motile forms regardless of the overall spermatozoal density, implying that a proportion of unexplained infertility is due to a disorder of spermatozoa reflected by reduced motility. Pregnancies were achieved in 5 of 26 cases with chronic oligospermia, including 2 where oligospermia was very pronounced (less than or equal to 5 million motile spermatozoa per milliliter).

Pituitary down-regulation using leuprolide for the intensive ovulation management of poor prognosis patients having in vitro fertilization (IVF)-related treatments

A review of 118 treatment cycles in 115 women under prolonged GnRH analogue (GnRHa; leuprolide) treatment is presented. Patients were selected for treatment primarily on the grounds of poor previous response to stimulation (n=40). advanced age (>35 years; n=29), previous premature luteinizing hormone (LH) surge (n=30), polycystic ovarian disease (PCO; n=12), and elevaved androgens without evidence of PCO (n=5). An overall pregnancy rate of 28.8% per treatment cycle was attained, compared with a pregnancy rate of 6.2% (6/97, of which none went to term) in the previous completed treatment cycle for the same patients. Ovarian response, as measured by oocytes recovered and maximum estradiol levels observed, was significantly improved in all groups and this was associated with a prolonged follicular phase, significantly more human menopausal gonadotropin (hMG) stimulation and a relatively high incidence of ovarian hyperstimulation, particularly in pregnant patients Of specific techniques in the GnRHa cycle, GIFT produced a pregnancy rate per treatment of 50% (10/20); IVF-ET, 22% (8/36); PROST, 28% (13/46); and TEST 19% (3/16). No cyles were abandoned, compared with a cancellation rate of 24% in previous cycles without GnRHa. Patients with PCO performed paricularly well on GnRHa management, with a pregnancy rate per treatment of 58% (7/12). Pregnancy rates per treatment for the other groups were as follows: elevated age, 27% (9/33), high androgen, 40% (2/5); premature LH surges, 32% (9/28); and poor responders, 17.5% (7/40). A comparison using patients undertaking IVF-ET cycles in 1987 and 1988 shows that the use of GnRHa treatment in the poorprognosis groups lifts their performance into line with that seen in the “good”-prognosis groups. We conclude that pituitary down-regulation with GnRHa (long regimen) offers significant advantages for ovarian management in most groups of infertility patients and it is now being evaluated for routine use in the majority of cases in our practice.

The treatment of normospermic infertility by gamete intrafallopian transfer (GIFT)

Summary. Gamete intrafallopian transfer (GIFT) was applied in 207 treatment cycles in 73 couples. The pregnancy rate in cycles with only one (2/21, 9·5%) or two (2/29, 6·9%) oocytes transferred was significantly less than that in which four oocytes (36/116, 31·0%) were replaced. The collection of more than four oocytes did not influence the pregnancy rate in that treatment cycle. The overall pregnancy rate was 24·2% (50 of 207) and was similar in the four infertility groups studied (non‐occlusive tubal disorders, endometriosis, cervical factor and unexplained infertility) with 28 (56%) of the pregnancies delivered at 20 weeks. The pregnancy wastage included 4 (8%) ectopic pregnancies and 3 (6%) late pregnancy losses. The 12 multiple pregnancies occurred following the transfer of three and four oocytes.

The successful recovery and fertilization of oocytes from the pouch of Douglas

Two groups of women were studied in whom a proportion of follicles had either ovulated spontaneously (7 women) or ruptured during manipulation at laparoscopy (30 women), and oocytes were recovered from the pouch of Douglas. There were no significant differences in the fertilization rates of oocytes collected in the pouch of Douglas from ovulated follicles, compared with those from the remaining intact follicles [15/20 (75%) vs 14/20 (70%)]. Also there was no significant difference between the fertilization rate of oocytes from follicles ruptured at the time of oocyte collection and that of oocytes from inlact follicles [25/38 (66%) vs 101/140 (72%)]. One woman became pregnant, following the transfer of four four-cell embryos, all derived from spontaneously ovulated oocytes found in the pouch of Douglas. She gave birth to a baby girl. The present study has shown that (1) oocytes may still be retrieved from the pouch of Douglas, despite follicle dispersal; (ii) these oocytes can be fertilized; and (iii) the embryos derived from ovulated oocytes recovered from the pouch of Douglas may generate an ongoing pregnancy following in vitro fertilization and embryo transfer.

Sperm stimulants can improve fertilization rates in male-factor cases undergoing IVF to the same extent as micromanipulation by partial zona dissection (PZD) or subzonal sperm insemination (SUZI): A randomized controlled study

PurposeOur purpose was to evaluate the efficacy of direct insemination (IVF), micromanipulation by partial zona dissection (PZD), and subzonal sperm insemination (SUZI) using spermtreated with pentoxifylline (PF) ± 2-deoxyadenosine (2DA).ResultsThe overall fertilization rate achieved was similar for all three fertilization techniques (33.1, 30.2, and 26.9% for IVF, SUZI, and PZD, respectively). Patients who had reduced fertilization in previous IVF attempts showed improved fertilization with sperm stimulants, either PF alone or PF in combination with 2DA in standard IVF. In certain cases, SUZI or PZD gave significantly improved fertilization rates in comparison to IVF.ConclusionSelective use of sperm stimulants in IVF can achieve fertilization for the majority of male-factor cases. However, PZD and SUZI techniques are useful, especially when sperm stimulants fail to achieve fertilization or achieve poor fertilization in direct insemination.