Successful pregnancy after artificial insemination in a case of human seminal plasma allergy

Abstract

Human seminal plasma allergy in women is uncommon, but causes a variety of serious reactions, including urticaria, dyspnea and vomiting, in those that are affected. Semen barriers, such as condoms, are the most widely advocated method for avoiding these reactions. However, this is not acceptable to couples who wish to have children. We present a case of a woman with human seminal plasma allergy who became pregnant after the eighth cycle of artificial insemination using washed sperm from her spouse. (Reprod Med Biol 2008; 7: 119–122)

INTRODUCTION

ALLERGIC REACTIONS TO human seminal fluid are uncommon, but a number of reports have appeared in the literature. ¹ , ² , ³ , ⁴ Minor complaints of this allergy are local reactions, including itching, burning, erythema and edema in the vulvar region or other semen‐contact sites. Some reports indicate generalized systemic reactions, such as urticaria, dyspnea and vomiting. ¹ , ³ These are a rare phenomenon, and local reactions may be more frequent with many undiagnosed cases.

Allergic reactions to human seminal fluid range from local swelling to generalized systemic changes. ¹ Local symptoms are presumably much more frequent than systemic reactions, but may be largely under diagnosed. For diagnosis, a skin prick test needs to be conducted. ⁵ , ⁶ The mechanism of sensitization in seminal plasma allergy is unclear, but the most common clinical picture is IgE‐mediated type I allergy; although type III and IV immunological reactions have also been documented. ⁷ Several seminal plasma allergens have been detected and their molecular masses range from 12 to 75 kDa. ⁸

Therapeutic options include allergen avoidance by using sperm barriers as well as attempts at desensitization. The former approach relying on condoms is the most widely advocated method for avoiding reactions, but this is clearly not acceptable to couples wishing to have children. Other options, including immunotherapy, have been described as effective modalities. ⁹ , ¹⁰ , ¹¹ Recently, artificial insemination has also been reported in affected individuals. ⁵ , ⁶ , ¹²

We present a case of a successful pregnancy after artificial insemination using sperm prepared by washing following diagnosis of human seminal plasma allergy using a skin patch test.

CASE REPORT

A 35‐YEAR‐OLD NULLIGRAVIDA visited Nagoya City University Hospital because of anaphylactic reactions after sexual intercourse. She had a history of postcoital general urticaria, dyspnea and vomiting. These symptoms occurred immediately after ejaculation during intercourse without condoms and she said that the use of condoms completely abolished the symptoms. She had a history of atopic dermatitis, bronchial asthma and a food allergy to carapaces.

This patient wanted to become pregnant, so an allergy study was carried out, after which we planned an artificial insemination program. For skin patch testing, seminal fluid was collected by masturbation and the total volume, sperm concentration, progression and motility were evaluated. Motile sperm were collected using the swim‐up technique as follows: the sample was diluted with the same amount of P‐1 medium (IS Japan, Saitama, Japan) and centrifuged at 250 g for 15 min at room temperature, and then the pellet was carefully moved to the bottom of a 15 mL tube (FALCON 352095; Becton Dickinson, Franklin Lakes, NJ, USA) containing 0.8 mL P‐1 medium. Care was taken to avoid bubbles and to not disturb the interface between the pellet and the medium. After incubation for 30 min, the top layer of the medium containing the motile sperm was aspirated. The motile sperm suspension was then centrifuged at 250 g for 15 min and the supernatant was removed and the sperm pellet was washed with 1 mL P‐1 medium at 250 g for 15 min.

Skin patch tests were carried out to diagnose the allergen, that is, seminal plasma or sperm. Patch sites were scored according to the key in Table 1. ¹³ Stripping patch tests with fresh semen showed strong positive results, while 10% diluted semen and the sperm pellet showed weak positive results after 15 min (Fig. 1, Table 2). There was no reaction with each patch after 24 h.

Table 1.

Patch testing interpretation key

–	Negative reaction
+/–	Weak erythema only
+	Weak (non‐vesicular) positive reaction; erythema, infiltration, possibly papules
++	Strong (vesicular) positive reaction; erythema, infiltration, papules, vesicles
+++	Extreme positive reaction; bullous reaction
IR	Irritant reactions of different types

Interpretation key of the International Contact Dermatitis Research Group. ¹¹

Figure 1.

(a) Results of stripping patch tests with semen and sperm pellet. The patch site with fresh semen showed erythema with papules and the site with ×1 sperm showed erythema. (b) Results of stripping patch tests with 10% diluted semen and sperm pellet. The patch site with 10% diluted semen showed erythema and the site with 10% diluted sperm showed weak erythema.

Table 2.

Results of stripping patch tests with semen and sperm pellets

Concentration	Semen	Sperm
1:100	–	–
1:10	+	+/–
1:1	++	+

See Table 1 for a description of the reactions.

The pellet fractions were washed in P‐1 medium once to four times. The results of the stripping patch tests with twice‐washed pellets were positive, but after four washes negative results were obtained after 15 min (Fig. 2). There was no reaction with each patch after 24 h.

Figure 2.

Results of stripping patch tests with washed sperm. The patch site with twice‐washed sperm showed erythema and the site with sperm that was washed four times showed a negative reaction.

From these results, we decided to use sperm that had been washed four times for artificial insemination. To determine the optimal day of artificial insemination, follicle growth was monitored by vaginal ultrasonography from the 12th day of the menstrual cycle to estimate the day of ovulation. Artificial insemination was conducted when one leading follicle measuring >18 mm in diameter was detected.

Ejaculate from the patient's spouse was collected by masturbation on the day of artificial insemination. The specimens were processed as detailed above and the sperm were washed four times with P‐1 medium. The pellet was resuspended in P‐1 medium to a total volume of 0.4 mL. An examination of the specimens for insemination was carried out to determine the post‐preparation concentration and motility. The results from before the treatment were: volume 1.5 mL, concentration 352 × 10⁶/mL and motility 13.6%. The results after washing four times were: volume 0.1 mL, concentration 198 × 10⁶/mL and motility 98.6%. When the intrauterine placement of the spermatozoa was carried out, the patient was monitored using a percutaneous oxygen saturation monitor and electrocardiograms to detect symptoms of anaphylaxis. In addition, the intravenous route was secured. Ovulation was triggered with an intramuscle injection of 10 000 IU human chorionic gonadotrophin (hCG) (Mochida Pharmaceutical, Tokyo, Japan) when follicles remained on the day of artificial insemination. As a previous blood examination showed that the patient had luteal insufficiency, luteal function was supported with additional doses of 5000 IU hCG three times during one cycle. Eight artificial insemination cycles were carried out, the last of which resulted in a successful pregnancy. Subsequently the patient gave birth to a healthy, full‐term male baby.

DISCUSSION

THE PRESENT CASE highlights the success of artificial insemination using washed sperm to achieve pregnancy in a woman with human seminal plasma allergy. Our case has similarities to the first successful pregnancy using this methodology reported by Shapiro et al. ¹² In their case, seven cycles of artificial insemination were carried out before a pregnancy was achieved.

The alternative is to try immunotherapy to treat human seminal allergy. ³ Many attempts have been described administering protein fractions of seminal fluid and prepared sperm extract. ⁷ , ¹¹ , ¹⁴ In recent studies, local vaginal desensitization has been reported. ⁷ , ⁹ , ¹⁰ This treatment option does not require complicated preparation and can be an alternative for treating seminal plasma allergic patients. To maintain the tolerant state after all these treatments, patients need to have regular unprotected sexual activity.

In the present case, we selected artificial insemination with washed sperm because the patient wished to become pregnant as soon as possible and had no request for sexual intercourse without a semen barrier. From the result of skin patch tests, the patient was allergic to seminal plasma, not sperm, so we washed sperm repeatedly with culture medium to remove the seminal plasma. Despite the frequent handling, sperm concentration and motility were sufficient for artificial insemination. Our case indicates that the skin patch test is useful for the diagnosis of human seminal allergy despite differences between the skin and the vaginal mucous membrane. At first we were concerned that the patient might develop allergy symptoms after artificial insemination because of the difference in absorption between the skin and the vaginal mucous membrane. Thus, we carefully monitored for reactions after intrauterine placement of the spermatozoa was carried out. From the lack of symptoms observed, we conclude that it is useful and safe to determine the frequency of washing sperm from skin patch test results. Although eight cycles of artificial insemination were needed for a successful pregnancy, this therapy can be considered as an alternative for patients with human seminal plasma allergies who wish to become pregnant safely.